THE SYSTEMIC INFLAMMATORY RESPONSE TO CARDIOPULMONARY BYPASS (1997-1999)
1
NLM CIT. ID: 99127711
TITLE: The platelet in cardiopulmonary bypass.
AUTHORS: Weerasinghe A; Taylor KM
AUTHOR AFFILIATION:
Department of Cardiothoracic Surgery, Imperial College of Science,
Technology and Medicine, University of London, Hammersmith Hospital,
England.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
ABSTRACT:
Platelets are the smallest of the blood cells and are known to be
activated during cardiopulmonary bypass. They play a role in many
associated complications. Both quantitative and qualitative platelet
defects have been demonstrated, resulting in microvascular hemorrhage
and thromboembolism. As their interactions with endothelium and other
blood cells are unraveled, the important contribution they make
toward the systemic inflammatory response to operation seen in
cardiopulmonary bypass is increasingly evident. In this review, we
consider platelet activation during cardiopulmonary bypass, the
resultant clinical effects, and potential approaches to therapy and
prevention.
NLM PUBMED CIT. ID:
9930521
SOURCE: Ann Thorac Surg 1998 Dec;66(6):2145-52
2
NLM CIT. ID: 99112521
TITLE: Milrinone modulates endotoxemia, systemic inflammation, and subsequent
acute phase response after cardiopulmonary bypass (CPB).
AUTHORS: Mollhoff T; Loick HM; Van Aken H; Schmidt C; Rolf N
Tjan TD; Asfour B; Berendes E
AUTHOR AFFILIATION:
Klinik und Poliklinik fur Anasthesiologie und operative
Intensivmedizin, Westfalische Westfalische Wilhelms-Universitat
Munster, Germany. thomas.moellhoff@uni-muenster.de
PUBLICATION TYPES:
CLINICAL TRIAL
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Amyloid Protein AA)
0 (Interleukin-6)
0 (Phosphodiesterase Inhibitors)
78415-72-2 (Milrinone)
9007-41-4 (C-Reactive Protein)
ABSTRACT:
BACKGROUND: Compromised splanchnic perfusion and the resulting
intestinal mucosal injury leads to a decreased mucosal barrier
function, which allows translocation of intestinal flora and
endotoxemia. The authors evaluated the effects of milrinone on
splanchnic oxygenation, systemic inflammation, and the subsequent
acute- phase response in patients undergoing coronary artery bypass
grafting. METHODS: This open, placebo-controlled randomized clinical
study enrolled 22 adult patients in two groups. Before induction of
anesthesia, baseline values were obtained and patients were
randomized to receive milrinone (30 microg/kg bolus administered
progressively in 10 min, followed by a continuous infusion of 0.5
microg x kg(-1) x min(- 1)) or saline. The following parameters were
determined: hemodynamics; systemic oxygen delivery and uptake;
arterial, mixed venous and hepatic venous oxygen saturation;
intramucosal pH (pHi); and mixed and hepatic venous plasma
concentrations of endotoxin, interleukin 6, serum amyloid A, and
C-reactive protein. RESULTS: Milrinone did not prevent
gastrointestinal acidosis as measured by pHi, but its perioperative
administration resulted in significantly higher pHi levels compared
with control. Venous and hepatic venous endotoxin and the interleukin
6 concentration were reduced significantly in the milrinone group.
Serum amyloid A values were attenuated in the milrinone group 24 h
after surgery. No significant differences could be seen in routinely
measured oxygen transport-derived variables. CONCLUSIONS:
Perioperative administration of low-dose milrinone may have
antiinflammatory properties and may improve splanchnic perfusion in
otherwise healthy patients undergoing routine coronary artery bypass
grafting.
NLM PUBMED CIT. ID:
9915315
SOURCE: Anesthesiology 1999 Jan;90(1):72-80
3
NLM CIT. ID: 99070032
TITLE: High-volume continuous hemofiltration during cardiopulmonary bypass
attenuates pulmonary dysfunction in neonatal lambs after deep
hypothermic circulatory arrest.
AUTHORS: Nagashima M; Shin'oka T; Nollert G; Shum-Tim D
Rader CM; Mayer JE Jr
AUTHOR AFFILIATION:
Department of Cardiovascular Surgery, Children's Hospital, Boston, MA
02115, USA.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 1.11.1.7 (Peroxidase)
0 (Lipid Peroxides)
ABSTRACT:
BACKGROUND: Cardiopulmonary bypass (CPB) induces an inflammatory
reaction that activates neutrophils and releases free radicals in
tissue. Ischemia-reperfusion further aggravates inflammation.
Hemofiltration (HF) could potentially remove inflammatory mediators
and reduce injury. This study assessed the effect of continuous
high-volume HF during CPB on systemic edema formation and pulmonary
function after deep hypothermic circulatory arrest (DHCA). METHODS
AND RESULTS: Anesthetized lambs (n = 16) underwent CPB with systemic
cooling (40 minutes), DHCA (120 minutes at 18 degrees C), and
rewarming (40 minutes). All animals were weaned from CPB and observed
for 3 hours after reperfusion. Continuous HF was used in 8 lambs at a
flow rate of 300 mL/kg per hour throughout CPB, simultaneously
replacing hemofiltration volume with a balanced salt solution (HF
group). In 8 control animals, no hemofiltration was performed.
Hematocrit remained at 23% to 25% during the experiment in both
groups. Pulmonary vascular resistance (PVR), lung dynamic compliance
(Cdyn), alveolar-arterial oxygen difference (AaDO2), and total body
water content (bioimpedance) were measured. Malondialdehyde (MDA), a
product of lipid peroxidation, was assayed in lung tissue. Percent
increase of body water content at 180 minutes of reperfusion was
significantly lower in the HF group than in control (132 +/- 2% vs
152 +/- 5%, P < 0.005). There was less of a rise in PVR compared with
baseline at 180 minutes of reperfusion in the HF group than in
control (131 +/- 8% vs 238 +/- 26%, P < 0.005). In addition, percent
recovery of Cdyn and AaDO2 in the HF group was preserved
significantly (respectively, P < 0.05) 2 hours after reperfusion than
in the control group. Lung tissue MDA in the HF group (46.2 +/- 12.6
vs 65.3 +/- 17.1 nmol/L per gram of tissue, P < 0.05) was
significantly lower than in the control group. CONCLUSIONS: High-
volume, continuous hemofiltration during CPB attenuates systemic
edema formation, pulmonary hypertension, the extent of lung
dysfunction, and depression of cardiac output and reduces free
radical-mediated tissue injury after CPB with DHCA. This technique
may have a clinical application to reduce the morbidity rate of CPB.
NLM PUBMED CIT. ID:
9852930
SOURCE: Circulation 1998 Nov 10;98(19 Suppl):II378-84
4
NLM CIT. ID: 99056160
TITLE: [Inflammatory response during cardiopulmonary bypass: neutrophil
apoptosis]
AUTHORS: Sakai Y; Watanabe T
AUTHOR AFFILIATION:
Department of Thoracic Surgery, Nagoya University School of Medicine,
Japan.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Jpn
ABSTRACT:
Cardiopulmonary bypass (CPB) is essential to open heart surgery.
However, CPB induces many types of inflammatory response, and may
contribute to the tissue injury and the development of postoperative
complications. On the other hand, the neutrophil responses to injury
and infection immediately and secretes elastases and cytokines
followed by prolongation of inflammatory changes, and programmed cell
death (apoptosis) of neutrophils is delayed by inflammatory response.
In this study, we evaluated the alternation of the neutrophil life
span during CPB. Peripheral blood was obtained from eight adult
patients before CPB, 1 hr and 2 hr after CPB start. After separation
of neutrophils, and incuvation in the presence of TNF-alpha for 3 hr,
we measured fluorescence-microscopically apoptosis rate (%A). %A
significantly decreased with time (before 9.7 +/- 2.3%, 1 hr 3.0 +/-
1.0%, 2 hr 1.5 +/- 0.6%, p < 0.05). We conclude that neutrophil
apoptosis was suppressed significantly during CPB. Systemic
inflammatory change induced by CPB may be prolonged with extended
life span of neutrophil.
NLM PUBMED CIT. ID:
9838781
SOURCE: Kyobu Geka 1998 Nov;51(12):1024-6
5
NLM CIT. ID: 98378289
TITLE: Procalcitonin as a marker of systemic inflammation after conventional
or minimally invasive coronary artery bypass grafting.
AUTHORS: Kilger E; Pichler B; Goetz AE; Rank N; Welte M
Morstedt K; Vetter HO; Godje O; Schmitz C; Lamm P; Engelschalk E
Muehlbeyer D; Frey L
AUTHOR AFFILIATION:
Department of Anesthesiology, Ludwig-Maximilians University, Munich,
Germany.
PUBLICATION TYPES:
CLINICAL TRIAL
CONTROLLED CLINICAL TRIAL
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Biological Markers)
0 (Glycoproteins)
0 (Protein Precursors)
56645-65-9 (procalcitonin)
9007-12-9 (Calcitonin)
ABSTRACT:
Cardiac surgery using cardiopulmonary bypass (CPB) often induces a
systemic inflammatory response syndrome (SIRS). The concept of
minimally invasive direct coronary artery bypass (MIDCAB) eliminates
cardiopulmonary bypass. We evaluated the perioperative time course of
procalcitonin (PCT) to compare the inflammatory response due to these
two different surgical procedures. 57 patients were studied: CABG
with CPB (n = 30), MIDCAB without CPB (n = 27). The following data
were measured preoperatively, after induction of anesthesia, after
separation from CPB in the CABG group or after left internal mammary
artery (LIMA)-to-left anterior descending artery (LAD) anastomosis in
MIDCAB group, and every 3 hours for the first 42 hours in the ICU:
PCT, C-reactive protein (CRP), body temperature, hemodynamic
parameters, and the need for catecholamines. Leucocyte counts were
measured daily. For statistical analyses the Friedmann, Wilcoxon, or
Mann-Whitney U tests were used. PCT in the CABG group rose to a
maximum of 2.0 ng/ml (median) at 15 hrs postoperatively. In the
MIDCAB group maximal PCT concentration was 0.7ng/ml (median) (p <
0.05). CRP was elevated to 17.1 mg/dl in the CABG and 18.5mg/dl in
the MIDCAB group (n.s.). The leucocyte counts were increased on day 2
in the CABG group (p < 0.05). In the CABG group about 25% of the
patients needed noradrenaline, but in the MIDCAB group none (p <
0.05). Body temperature did not differ between both groups. The
increase in PCT concentration was more pronounced after CABG,
indicating a reduced inflammatory response after MIDCAB. CRP was
increased after both procedures. PCT reflects the inflammatory
response after cardiac bypass surgery with or without CPB.
NLM PUBMED CIT. ID:
9714487
SOURCE: Thorac Cardiovasc Surg 1998 Jun;46(3):130-3
6
NLM CIT. ID: 98355166
TITLE: Inflammatory response after myocardial revascularization with or
without cardiopulmonary bypass.
AUTHORS: Brasil LA; Gomes WJ; Salomao R; Buffolo E
AUTHOR AFFILIATION:
Discipline of Cardiovascular Surgery, Escola Paulista de Medicina and
Sao Paulo Hospital, Federal University of Sao Paulo, Brazil.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Tumor Necrosis Factor)
ABSTRACT:
BACKGROUND: Tumor necrosis factor-alpha has been implicated in
complications seen after cardiac operations with cardiopulmonary
bypass. The release of tumor necrosis factor-alpha and its possible
effects were studied in patients undergoing coronary artery bypass
grafting with and without cardiopulmonary bypass. METHODS: Twenty
patients were studied, 10 with (group 1) and 10 without
cardiopulmonary bypass (group 2). Serial blood samples were obtained
before, during, and up to 48 hours after operation. Circulating tumor
necrosis factor- alpha levels, leukocyte counts, and erythrocyte
sedimentation rates were measured. Hemodynamic variables (blood
pressure and heart rate), temperature, orotracheal intubation time,
postoperative bleeding, and inotropic drug requirements were
compared. RESULTS: Serum levels of tumor necrosis factor-alpha were
detected in 6 patients (60%) in group 1 and none in group 2. The
patients in group 1 had more hypotension than those in group 2 (7.4
+/- 1.0 mm Hg versus 8.5 +/- 0.7 mm Hg), required more inotropic
drugs (8 patients versus 1 patient), and had a higher heart rate (114
+/- 8 beats per minute versus 98 +/- 10 beats per minute), a higher
temperature (37.1 degrees +/- 0.5 degrees C versus 36.6 degrees +/-
0.3 degrees C), increased postoperative bleeding (820 +/- 120 mL
versus 360 +/- 84 mL), a longer orotracheal intubation time (13.6 +/-
2.2 hours versus 9.3 +/- 1.4 hours), and a more pronounced
leukocytosis. CONCLUSIONS: Cardiopulmonary bypass induces the
whole-body inflammatory response through the release of tumor
necrosis factor alpha, resulting in adverse systemic effects.
NLM PUBMED CIT. ID:
9692438
SOURCE: Ann Thorac Surg 1998 Jul;66(1):56-9
7
NLM CIT. ID: 98347928
TITLE: Platelet activation and cytokine production during hypothermic
cardiopulmonary bypass--a possible correlation?
AUTHORS: Ferroni P; Speziale G; Ruvolo G; Giovannelli A
Pulcinelli FM; Lenti L; Pignatelli P; Criniti A; Tonelli E; Marino B
Gazzaniga PP
AUTHOR AFFILIATION:
Department of Experimental Medicine and Pathology, University of Rome
La Sapienza, Italy.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Cytokines)
0 (Polymers)
ABSTRACT:
Cardiopulmonary bypass (CPB) is associated with impaired platelet
function and a systemic inflammatory response. The present study was
designed to evaluate whether any correlation between platelet
activation and inflammatory response during CPB exists. The results
obtained from 8 patients undergoing hypothermic CPB for cardiac
surgery showed the occurrence of a moderate degree of platelet
activation during CPB, demonstrated by an increase of platelet CD62P
expression in correlation with an increase of beta-thromboglobulin
levels, with a concomitant decrease of in vitro platelet response.
Plasma IL-1beta levels significantly increased during CPB, with a
peak between 1 and 4 h after CPB. Similarly, IL-6 levels were
elevated 30 min from CPB starting, peaked at 4 h, and remained
elevated after 24 h. A direct correlation was found between plasma
IL-1beta and IL-6 levels. A significant correlation between plasma
IL-1beta and beta- thromboglobulin levels was also found. In turn,
plasma beta- thromboglobulin levels correlated with CD62P expression
on activated platelets. An inverse correlation was found between in
vitro platelet aggregation and plasma IL-1beta or IL-6 levels. From
the present results it may be speculated that platelet activation
during CPB may contribute, through the release of IL-1beta, to
activation of endothelial cells and subsequent release of other
cytokines with chemotactic and pro-inflammatory properties, thus
playing an important role in the inflammatory response associated
with CPB.
NLM PUBMED CIT. ID:
9684786
SOURCE: Thromb Haemost 1998 Jul;80(1):58-64
8
NLM CIT. ID: 98337207
TITLE: Perioperative predictors of acute cholecystitis after cardiovascular
surgery.
AUTHORS: Rady MY; Kodavatiganti R; Ryan T
AUTHOR AFFILIATION:
Department of Cardiothoracic Anesthesia, Cleveland Clinic Foundation,
Ohio, USA.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Vasoconstrictor Agents)
ABSTRACT:
OBJECTIVE: To determine the incidence, diagnostic features, and
perioperative predictors of acute cholecystitis after cardiovascular
surgery. DESIGN: Inception cohort study. SETTING: A tertiary care 54-
bed cardiothoracic ICU. PATIENTS: All patients admitted to an ICU
after cardiovascular surgery during a 42-month period. INTERVENTION:
Collection of relevant preoperative, operative, and ICU data from a
database and medical charts. PRIMARY OUTCOME: Postoperative acute
cholecystitis (AC). RESULTS: Out of 11,330 admissions, 876 patients
stayed in the ICU more than 7 days and 30 of them (3%) developed
postoperative AC. AC was diagnosed a median of 26 days after
cardiovascular surgery (interquartile range, 11 to 41 days). All
patients with AC developed at least two criteria of the systemic
inflammatory response syndrome (SIRS), and 16 of them (53%) were
vasopressor-dependent on the day of diagnosis. Trends in biochemical
testing of liver function were not diagnostic for AC. Death occurred
in seven of 17 patients (41%) who underwent cholecystectomy, three of
nine patients (33%) treated with percutaneous cholecystostomy, and
one of four patients (25%) treated conservatively (p=not
significant). Specific earlier predictors of AC were arterial
vascular disease, preoperative oxygen delivery less than 430 mL/min x
m2, longer times on cardiopulmonary bypass, surgical re-exploration,
ICU course complicated by cardiac arrhythmia, mechanical ventilation
> or = 3 days, bacteremia, and nosocomial infections. CONCLUSION: The
incidence of AC is low after cardiovascular surgery. Although SIRS
and hemodynamic instability were common at the time of diagnosis, the
delayed occurrence and lack of specificity of these features for AC
limited their utility for early diagnosis. Specific predictors of AC
should be sought in the ICU setting to identify patients who are at
risk for AC after cardiovascular surgery. When identified, such
predictors can prompt earlier diagnosis and treatment. Further
evaluation of the selection criteria for different treatment options
is needed in order to decrease the morbidity and mortality associated
with AC.
NLM PUBMED CIT. ID:
9674450
SOURCE: Chest 1998 Jul;114(1):76-84
9
NLM CIT. ID: 98329873
TITLE: Hyperprocalcitonemia in patients with noninfectious SIRS and pulmonary
dysfunction associated with cardiopulmonary bypass.
AUTHORS: Hensel M; Volk T; Docke WD; Kern F; Tschirna D
Egerer K; Konertz W; Kox WJ
AUTHOR AFFILIATION:
Department of Anaesthesiology and Intensive Therapy, University
Hospital Charite, Berlin, Germany.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Biological Markers)
0 (Protein Precursors)
9007-12-9 (Calcitonin)
ABSTRACT:
BACKGROUND: The incidence of noninfectious systemic inflammatory
response syndrome (SIRS) associated with coronary artery bypass
surgery and the potential role of several inflammatory parameters as
early markers of pulmonary dysfunction induced by cardiopulmonary
bypass (CPB) were investigated. METHODS: Forty patients undergoing
elective coronary artery bypass surgery were studied prospectively.
Perioperative lung function was monitored using the lung injury score
introduced by Murray and colleagues, by measuring venous admixture
(Qs/Qt), and, in some cases, by measuring extravascular lung water.
Serum concentrations of the inflammatory parameters (procalcitonin,
interleukin-6, sL-selectin, leukocyte elastase, neopterin, leukocyte
counts, and C-reactive protein) were determined sequentially. The
American College of Chest Physicians-Society of Critical Care
Medicine classification system was used to diagnose SIRS. RESULTS:
According to the entry criteria, SIRS developed in 17 (42%) patients
after operation. Nine patients of this group showed signs of acute
pulmonary impairment, whereas patients without SIRS had no lung
injury. In all patients with acute lung injury, distinct increases in
procalcitonin concentrations ranging from 5.1 to 14.3 ng/ml were
measured. In patients with SIRS but without acute lung injury and in
patients without SIRS, none or only negligible increases in serum
concentrations of procalcitonin were seen. Compared with
procalcitonin, other inflammatory parameters investigated were less
sensitive and less specific to indicate pulmonary dysfunction
secondary to CPB. CONCLUSIONS: Procalcitonin seems to be an
appropriate parameter indicating the early development of severe
noninfectious SIRS and for predicting pulmonary dysfunction secondary
to CPB.
NLM PUBMED CIT. ID:
9667299
SOURCE: Anesthesiology 1998 Jul;89(1):93-104
10
NLM CIT. ID: 98321702
TITLE: Interleukin-6 levels in serum and lung lavage fluid of children
undergoing open heart surgery correlate with postoperative morbidity.
AUTHORS: Hauser GJ; Ben-Ari J; Colvin MP; Dalton HJ
Hertzog JH; Bearb M; Hopkins RA; Walker SM
AUTHOR AFFILIATION:
Division of Pediatric Critical Care and Pulmonary Medicine, Georgetown
University Children's Medical Center, Washington, DC 20007, USA.
Hauserg@gunet.georgetown.edu
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Interleukin-6)
ABSTRACT:
OBJECTIVE: To evaluate the relationship of perioperative levels of
interleukin 6 (IL-6) in serum and bronchoalveolar fluid with
morbidity and mortality in children undergoing cardiopulmonary bypass
(CPB). DESIGN: Prospective, noninterventional study. SETTING:
Operating room and pediatric intensive care unit (PICU) of a
university hospital. Interventions: None. MEASUREMENTS AND RESULTS:
IL-6 levels were measured in serum and lung lavage fluid obtained
before, during, and after CPB using the B9.9 bioassay. Alveolar
epithelial lining fluid (AELF) volume was calculated using the urea
correction method. Mean intraoperative AELF IL-6 levels increased
fourfold compared to preoperative levels, and mean serum IL-6 levels
increased fivefold after CPB. Mean intraoperative AELF IL-6 levels
correlated with intraoperative blood transfusion (r2 = 0.18; p =
0.049) and duration of inotropic support (r2 = 0.29; p = 0.009),
mechanical ventilation (r2 = 0.24; p = 0.019), and PICU stay (r2 =
0.29; p = 0.008). Mean serum IL-6 levels 2 h after CPB correlated
with intraoperative blood transfusion (r2 = 0.3;p = 0.007), and with
Pediatric Risk of Mortality score on postoperative day 3 (r2 = 0.24;
p = 0.022), and were higher in patients with massive fluid retention
(p = 0.014) and in nonsurvivors (p = 0.003). CONCLUSIONS: Serum and
alveolar IL-6 levels increase after CPB, and correlate with
postoperative morbidity. Serum IL-6 levels also correlate with
mortality. They may be useful in assessing the severity of the
systemic inflammatory response after CPB.
NLM PUBMED CIT. ID:
9660265
SOURCE: Intensive Care Med 1998 May;24(5):481-6
11
NLM CIT. ID: 98273431
TITLE: [Surgery of acute aortic valve endocarditis: prognosis in paravalvular
abscess]
VERNACULAR TITLE:
Chirurgie der akuten Aortenklappenendokarditis: Prognose bei
paravalvularen Abszessen.
AUTHORS: Bauernschmitt R; DeSimone R; Lange R; Vahl CF
Thomas G; Hagl S
AUTHOR AFFILIATION:
Abteilung fur Herzchirurgie Chirurgische Universitatsklinik,
Heidelberg.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Ger
REGISTRY NUMBERS:
0 (Antibiotics, Combined)
ABSTRACT:
The occurrence of paravalvular abscesses in the course of an acute
endocarditis of the aortic valve indicates an advanced stadium of the
disease. The infection has spread beyond the limits of the valve
leaflets, and ongoing destruction of the paravalvular tissue is to be
expected, if the endocarditis is continually treated by antibiotics
alone. Surgery of acute endocarditis with paravalvular abscess,
however, supposedly carries an increased risk of early mortality and
late morbidity. The following prospective study was carried out to
determine whether a radical surgical approach together with
aggressive postoperative antibiotic therapy could help to improve
results. Between 1988 and 1995, 138 patients were operated during the
acute phase of infective endocarditis; in 102 the aortic valve was
involved. Among these, 44 had paravalvular abscesses at the time of
surgery. The mean age of both groups was the same, but there was a
higher rate of concomitant coronary artery disease, multiple valve
involvement, advanced NYHA-class, and staphylococcal disease among
the patients with abscesses. All interventions were carried out with
cardiopulmonary bypass and cardioplegic arrest. The aortic valve was
resected, abscesses were removed, and each part of potentially
infected or necrotic tissue was resected as complete as possible,
irrespective of the possibility to jeopardize the conduction system
or to create large tissue defects. The aortic valve was replaced with
a mechanical prosthesis in each case. The postoperative antibiotic
regimen was specifically directed against the microorganisms isolated
preoperatively; therapy was only modified, if signs of systemic
infection did not disappear three days after surgery. The operative
mortality was 10% among patients without an abscess and 11% in
patients with a paravalvular abscess. Early recurrent endocarditis
was recorded in two patients without and in only one patient with an
abscess. Late recurrent endocarditis was noted in three patients;
none of them had abscesses at the time of surgery. We conclude that
the operative risk of acute endocarditis of the aortic valve with a
paravalvular abscess does not have to be inevitably higher compared
to cases without paravalvular involvement. To achieve these results,
it is necessary to use a radical surgical approach and to adjust
postoperative antibiotic therapy, if infectious signs do not
disappear shortly after surgery.
NLM PUBMED CIT. ID:
9610511
SOURCE: Z Kardiol 1998 Apr;87(4):276-82
12
NLM CIT. ID: 98226705
TITLE: Reduced ex vivo interleukin-8 production by neutrophils in septic and
nonseptic systemic inflammatory response syndrome.
AUTHORS: Marie C; Muret J; Fitting C; Losser MR; Payen D
Cavaillon JM
AUTHOR AFFILIATION:
Unite d'Immuno-Allergie, Institut Pasteur, Paris; and the Department
of Anaesthesia and Intensive Care Medicine, Hopital Lariboisiere,
Paris, France.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Endotoxins)
0 (Interleukin-8)
130068-27-8 (Interleukin-10)
ABSTRACT:
Ex vivo cytokine production by circulating lymphocytes and monocytes
is reduced in patients with infectious or noninfectious systemic
inflammatory response syndrome. Very few studies have addressed the
reactivity of polymorphonuclear cells (PMN). To analyze further the
relative contribution of systemic inflammatory response syndrome
alone or in combination with infection we studied the interleukin-8
(IL-8) production by PMN isolated from patients who had undergone
cardiac surgery with cardiopulmonary bypass (CPB) and patients with
sepsis. Cells were activated with either lipopolysaccharide (LPS) or
heat- killed streptococci. Compared with healthy controls, the
release of IL- 8 by PMN in both groups of patients was significantly
reduced whether activated by LPS, independently of its concentration
and origin, or by heat-killed streptococci. These observations
suggest that stressful conditions related to inflammation,
independently of infection, rapidly dampened the reactivity of
circulating PMN. We investigated whether the observed diminished
reactivity of PMN might reflect an endotoxin tolerance phenomenon.
Our in vitro experiments with PMN from healthy controls indicated
that PMN could not be rendered tolerant stricto sensu. However, our
data suggested that LPS-induced mediators such as IL-10 may be
responsible for the observed anergy in patients.
NLM PUBMED CIT. ID:
9558403
SOURCE: Blood 1998 May 1;91(9):3439-46
13
NLM CIT. ID: 98255747
TITLE: Systemic inflammation present in patients undergoing CABG without
extracorporeal circulation.
AUTHORS: Fransen E; Maessen J; Dentener M; Senden N; Geskes G
Buurman W
AUTHOR AFFILIATION:
Department of Cardiopulmonary Surgery, University Hospital Maastricht,
The Netherlands.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (bactericidal permeability increasing protein)
0 (lipopolysaccharide-binding protein)
0 (Acute-Phase Proteins)
0 (Blood Proteins)
0 (Carrier Proteins)
0 (Interleukin-6)
9007-41-4 (C-Reactive Protein)
ABSTRACT:
STUDY OBJECTIVES: This study was conducted to evaluate to what extent
the cardiopulmonary bypass (CPB) procedure in patients undergoing
coronary artery bypass grafting (CABG) contributes to the systemic
inflammatory response. Therefore, we measured bactericidal
permeability increasing protein (BPI) as an indicator of neutrophil
activation, interleukin 6 as inducer of the acute phase response, and
lipopolysaccharide binding protein and C-reactive protein as
parameters of the acute phase response in patients undergoing CABG
either with or without the use of CPB. DESIGN: Prospective study.
SETTING: Cardiopulmonary surgery department in a university hospital.
PATIENTS: Sixteen patients undergoing elective CABG were included.
Eight patients underwent surgery with CPB, and eight patients
underwent surgery without CPB (non-CPB). INTERVENTIONS: In the CPB
group, blood samples were taken upon induction of anesthesia, at the
start of aortic cross- clamping, at aortic unclamping, and 0.5, 4, 8,
and 18 h thereafter. In the non-CPB group, blood samples were taken
upon induction of anesthesia, and 0.5, 4, 8, and 18 h after
completion of the bypass graft anastomoses. MEASUREMENTS AND RESULTS:
BPI release from neutrophil granules markedly increased during
surgery in CPB patients but not in non-CPB patients. The increase in
acute phase reactants, however, was the same in both patient groups.
CONCLUSIONS: These data indicate that the acute phase response in
CABG patients, which has historically been ascribed to the CPB
procedure, is predominantly caused by the surgical procedure per se.
Early neutrophil activation, however, is seen only when
extracorporeal circulation is used.
NLM PUBMED CIT. ID:
9596308
SOURCE: Chest 1998 May;113(5):1290-5
14
NLM CIT. ID: 98257220
TITLE: Cardiopulmonary bypass circuit treated with surface-modifying
additives: a clinical evaluation of blood compatibility.
AUTHORS: Gu YJ; Boonstra PW; Rijnsburger AA; Haan J
van Oeveren W
AUTHOR AFFILIATION:
Department of Cardiothoracic Surgery, Thorax Center, University
Hospital Groningen, The Netherlands.
PUBLICATION TYPES:
CLINICAL TRIAL
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 3.4.21.37 (Leukocyte Elastase)
0 (beta-Thromboglobulin)
0 (prothrombin fragment 1.2)
0 (Complement Membrane Attack Complex)
0 (Interleukin-8)
0 (Peptide Fragments)
0 (Platelet Glycoprotein GPIIb-IIIa Complex)
0 (Surface-Active Agents)
80295-42-7 (Complement 3a)
80295-49-4 (Complement 4a)
9001-26-7 (Prothrombin)
ABSTRACT:
BACKGROUND: The cardiopulmonary bypass (CPB) circuit induces blood
activation and a systemic inflammatory response in cardiac surgical
patients. The CPB circuit treated with surface-modifying additive
(SMA) has been found to reduce blood activation by in vitro and ex
vivo experiments. This study evaluates the surface thrombogenicity
and complement activation of SMA circuits during clinical CPB.
METHODS: Twenty patients undergoing coronary artery bypass grafting
were randomly divided into two groups. In the SMA group (n = 10), all
blood- contacting surfaces in the CPB circuit were treated or coated
with SMA, whereas in the control group (n = 10) patients were
perfused with an identical circuit without treatment. RESULTS: During
CPB, platelet count and beta-thromboglobulin were found similar in
both the SMA and the control groups. Prothrombin activation indicated
by fragment F1 + 2 was found less in the SMA group (p < 0.05). After
CPB, platelet deposition on the CPB circuit was significantly less (p
< 0.05) in the SMA group than in the control group as assessed by the
labeled monoclonal antibody against platelet glycoprotein IIIa.
Complement activation identified by C3a and terminal complex C5b-9
did not differ between the two groups, but C4a generation was less in
the SMA group (p < 0.05). Leukocyte activation identified by elastase
and cytokine release indicated by interleukin-8 were found uniformly
in both groups. Postoperatively, chest tube drainage, blood
transfusion, duration of ventilatory support, as well as the
intensive care unit and hospital stay were not significantly
different between the two groups. CONCLUSIONS: These preliminary
clinical results suggest that SMA inhibits platelet interaction with
the biomaterial surface of the CPB circuit. Complement activation
assessed by the terminal complement complex is not influenced by SMA.
The clinical benefit of this surface- modifying technique has yet to
be assessed in a larger population of patients undergoing cardiac
operations.
NLM PUBMED CIT. ID:
9594864
SOURCE: Ann Thorac Surg 1998 May;65(5):1342-7
15
NLM CIT. ID: 98242874
TITLE: Cardiopulmonary bypass-induced inflammation: is it important?
AUTHORS: Hill GE
AUTHOR AFFILIATION:
Department of Anesthesiology, University of Nebraska Medical Center,
Omaha 68198-4455, USA.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 1.14.13.39 (Nitric-Oxide Synthase)
0 (Anti-Inflammatory Agents)
0 (Cytokines)
0 (Endotoxins)
0 (Inflammation Mediators)
0 (Interleukin-1)
0 (Interleukin-6)
0 (Macrophage-1 Antigen)
0 (Ribonucleosides)
0 (Serine Proteinase Inhibitors)
0 (Tumor Necrosis Factor)
10102-43-9 (Nitric Oxide)
126547-89-5 (Intercellular Adhesion Molecule-1)
2627-69-2 (acadesine)
360-97-4 (Aminoimidazole Carboxamide)
ABSTRACT:
The systemic endotoxemia that occurs with the institution of
cardiopulmonary bypass (CPB) is a potent stimulus for the release of
proinflammatory cytokines, including tumor necrosis factor-alpha
(TNF- alpha), interleukin-1 (IL-1), and IL-6. Raised IL-6 levels have
been reported to correlate with post-CPB left ventricular wall-motion
abnormalities and myocardial ischemic episodes.
Neutrophil-endothelial adhesion is strongly implicated in the
inflammation and reperfusion injury that may follow a period of CPB,
and organ injury is thought to be, in part, neutrophil mediated. The
CD11b neutrophil integrin primarily responsible for endothelial
binding is rapidly, permanently, and preferentially expressed on
exposure to cytokines. The endothelial ligand intercellular adhesion
molecule-1 is also upregulated by cytokine exposure. Nitric oxide
(NO) synthesized by the vascular endothelium can inhibit
neutrophil-endothelial adhesion by downregulating CD11b/CD18 receptor
expression and inhibit platelet activation. The cytokines TNF-alpha,
IL-1, and endotoxin can cause the induction of NO synthase and the
release of large amounts of NO that may cause tissue injury. Various
treatment strategies to reduce CPB- induced inflammation provide
evidence to support the causal relationship between CPB-activated
cytokine release, neutrophil activation, and stimulation of increased
NO synthesis. The significant reductions in TNF-alpha and IL-6 levels
with hemofiltration during CPB in children are associated with
improved hemodynamics and early postoperative oxygenation. Acadesine
can inhibit the upregulation of leukocyte CD11b adhesion receptors,
and treatment in patients before and during surgery can reduce early
cardiac death, myocardial infarction, and combined adverse
cardiovascular outcomes. Recent data suggest that administration of
the serine protease inhibitor aprotinin to patients undergoing
myocardial revascularization with CPB can reduce TNF-alpha blood
levels and blunt neutrophil CD11b upregulation. Preliminary data
suggest that aprotinin can inhibit cytokine-induced nitric oxide
synthase expression and subsequent NO production by murine bronchial
epithelial cells. These effects may explain some of the reported
antiinflammatory effects of the serine protease inhibitors.
NLM PUBMED CIT. ID:
9583572
SOURCE: J Cardiothorac Vasc Anesth 1998 Apr;12(2 Suppl 1):21-5
16
NLM CIT. ID: 98222862
TITLE: Brain damage during cardiopulmonary bypass.
AUTHORS: Taylor KM
AUTHOR AFFILIATION:
National Heart and Lung Institute, Imperial College of Science,
Technology and Medicine at Hammersmith Hospital, London, England.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
ABSTRACT:
The development of systems that allow cardiopulmonary bypass have been
responsible for the growth of our specialty. In recent years
continuing reduction in the mortality associated with cardiac
operations has reinforced our confidence in the reliability and
safety of perfusion equipment. Cardiac surgeons are aware that the
mortality for most cardiac surgical procedures has decreased
dramatically and overall morbidity has been reduced significantly.
However, it is still clear that cardiopulmonary bypass techniques are
not perfect. Indeed, it is fair to say that the period of bypass
still contributes to significant morbidity in most patients. In
particular, cerebral injury, the focus of this review, is a
significant problem for patients and their caregivers and for funding
of health-care systems. Incidence rates for stroke are around 2% to
3%, with increased risk in elderly patients and other high-risk
groups. This relatively low incidence of what is universally
recognized as a serious complication may be contrasted with the much
higher reported incidence of cognitive defects assessed by
neuropsychologic testing. The incidence of cognitive defects is as
high as 60% at 8 days postoperative with reduction to 25% to 30%
incidence at 8 weeks and 12 months. There are a variety of ways, at
least potentially, in which the brain may be injured during an
operation with cardiopulmonary bypass, including reduced cerebral
blood flow, microembolism and macroembolism, and a systemic
inflammatory response. These mechanisms interrelate and produce
synergistic, cumulative effects on brain function during and after
the operation. Reducing the incidence and effects of this altered
brain function will rely on both preventive and therapeutic
strategies. These, in turn, must be based on an understanding of the
pathophysiology of these mechanisms of cerebral injury and directed
toward ways to optimize cerebral perfusion, minimize embolic vascular
occlusion, and develop pharmacologic approaches to modify the
systemic inflammatory response.
NLM PUBMED CIT. ID:
9563398
SOURCE: Ann Thorac Surg 1998 Apr;65(4 Suppl):S20-6; discussion S27-8
17
NLM CIT. ID: 98143800
TITLE: Complement and contact activation during cardiovascular operations in
infants.
AUTHORS: Sonntag J; Dahnert I; Stiller B; Hetzer R; Lange PE
AUTHOR AFFILIATION:
Department of Neonatology, Virchow-Charite-Hospital, Humboldt
University, Berlin, Germany.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 3.4.21.38 (Factor XIIa)
EC 3.4.21.47 (Complement Factor B)
9007-36-7 (Complement)
9055-02-1 (Prekallikrein)
ABSTRACT:
BACKGROUND: By comparing the results of cardiac operations with or
without cardiopulmonary bypass (CPB) in infants in a prospective
study, we sought to determine which part of the postoperative
systemic inflammatory response was caused by CPB. METHODS:
Thirty-five patients were divided into two groups: 11 infants
operated on without CPB and 24 infants operated on with CPB. Blood
samples were drawn before, during, and after the operation. We
assessed complement function and the concentrations or activities of
C1q, C3, C4, C1 inhibitor, factor B, the activated split product C3a,
and prekallikrein and factor XIIa of the contact system. RESULTS: All
of the patients exhibited a decrease of complement proteins. This was
greater in infants who underwent CPB. A increase in C3a and factor
XIIa and changes in prekallikrein activity occurred only in infants
during CPB. CONCLUSIONS: Complement activation occurs in all infants,
but is significantly higher in the group with CPB. Contact activation
only occurs in patients who undergo CPB. Thus, the inflammatory
response is caused by the use of a CPB circuit and to a lesser degree
by surgical procedures and anesthesia.
NLM PUBMED CIT. ID:
9485258
SOURCE: Ann Thorac Surg 1998 Feb;65(2):525-31
18
NLM CIT. ID: 98143781
TITLE: Reduction of the inflammatory response in patients undergoing
minimally invasive coronary artery bypass grafting.
AUTHORS: Gu YJ; Mariani MA; van Oeveren W; Grandjean JG
Boonstra PW
AUTHOR AFFILIATION:
Department of Cardiothoracic Surgery, Thorax Center, University
Hospital, Groningen, The Netherlands.
PUBLICATION TYPES:
CLINICAL TRIAL
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 3.4.21.37 (Leukocyte Elastase)
0 (beta-Thromboglobulin)
0 (Inflammation Mediators)
80295-42-7 (Complement 3a)
ABSTRACT:
BACKGROUND: The aim of this prospective study was to determine whether
the inflammation-associated clinical morbidity as well as the
subclinical markers of the inflammatory response are reduced in
patients who undergo minimally invasive coronary artery bypass
grafting without cardiopulmonary bypass. METHODS: From June 1995 to
June 1996, 62 consecutive patients with isolated stenosis of the left
anterior descending coronary artery were assigned randomly to two
groups: 31 patients underwent minimally invasive coronary artery
bypass grafting and 31 patients underwent conventional coronary
artery bypass grafting with cardiopulmonary bypass. In a subgroup of
10 patients in each group, subclinical markers were measured to
determine the level of the inflammatory response generated during the
operation. RESULTS: In the group that underwent minimally invasive
coronary artery bypass grafting, leukocyte elastase, platelet
beta-thromboglobulin, and complement C3a were unchanged at the end of
the procedure compared with their baseline concentrations, whereas
these inflammatory markers were increased significantly in the group
that underwent conventional coronary artery bypass grafting with
cardiopulmonary bypass. The patients who underwent minimally invasive
coronary artery bypass grafting had a shorter duration of operation
(104 +/- 28 versus 140 +/- 28 minutes; p < 0.01), less blood loss
(312 +/- 167 versus 788 +/- 365 mL; p < 0.01), shorter ventilatory
support (7.7 +/- 4.1 versus 12.9 +/- 3.4 hours; p < 0.01), and a
shorter postoperative hospital stay (4.4 +/- 1.7 versus 7.7 +/- 2.6
days; p < 0.01) than the patients who underwent the conventional
procedure. CONCLUSIONS: These data suggest that patients who undergo
minimally invasive coronary artery bypass grafting have a significant
reduction in the systemic inflammatory response, postoperative
morbidity, and hospital stay compared with patients who undergo
conventional coronary artery bypass grafting with cardiopulmonary
bypass.
NLM PUBMED CIT. ID:
9485239
SOURCE: Ann Thorac Surg 1998 Feb;65(2):420-4
19
NLM CIT. ID: 98136591
TITLE: Controlling the complement system in inflammation.
AUTHORS: Kirschfink M
AUTHOR AFFILIATION:
Institute of Immunology, University of Heidelberg, Germany.
k92@ix.urz.uni-heidelberg.de
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Anaphylatoxins)
0 (Complement Inactivators)
0 (DNA, Complementary)
0 (Receptors, Complement)
ABSTRACT:
Inappropriate or excessive activation of the complement system can
lead to harmful, potentially life-threatening consequences due to
severe inflammatory tissue destruction. These consequences are
clinically manifested in various disorders, including septic shock,
multiple organ failure and hyperacute graft rejection. Genetic
complement deficiencies or complement depletion have been proven to
be beneficial in reducing tissue injury in a number of animal models
of severe complement- dependent inflammation. It is therefore
believed that therapeutic inhibition of complement is likely to
arrest the process of certain diseases. Attempts to efficiently
inhibit complement include the application of endogenous soluble
complement inhibitors (C1-inhibitor, recombinant soluble complement
receptor 1- rsCR1), the administration of antibodies, either blocking
key proteins of the cascade reaction (e.g. C3, C5), neutralizing the
action of the complement-derived anaphylatoxin C5a, or interfering
with complement receptor 3 (CR3, CD18/11b)-mediated adhesion of
inflammatory cells to the vascular endothelium. In addition,
incorporation of membrane-bound complement regulators (DAF-CD55,
MCP-CD46, CD59) has become possible by transfection of the
correspondent cDNA into xenogeneic cells. Thereby, protection against
complement-mediated inflammatory tissue damage could be achieved in
various animal models of sepsis, myocardial as well as intestinal
ischemia/reperfusion injury, adult respiratory distress syndrome,
nephritis and graft rejection. Supported by results from first
clinical trials, complement inhibition appears to be a suitable
therapeutic approach to control inflammation. Current strategies to
specifically inhibit complement in inflammation have been discussed
at a recent meeting on the 'Immune Consequences of Trauma, Shock and
Sepsis', held from March 4-8, 1997, in Munich, Germany. The Congress
(chairman: E. Faist, Munich, Germany), which was held in close
cooperation with various national and international shock and trauma
societies, was attended by about 2000 delegates from 40 countries.
The major objective of the meeting was to provide an overview on the
most state-of-the-art methods to prevent multiple organ dysfunction
syndrome (MODS)/multiple organ failure (MOF) following the systemic
inflammatory response (SIRS) to severe trauma. One of the largest
symposia held within the Congress was devoted to current aspects of
controlling complement in inflammation (for abstracts see: Shock
1997, 7 Suppl., 71- 75). After providing the audience with
information on the scientific background by addressing the clinical
relevance of complement activation (G.O. Till, Ann Arbor, MI, USA)
and discussing recent developments in modern complement diagnosis (J.
Kohl, Hannover, Germany), B.P. Morgan (Cardiff, UK) introduced the
symposium's special issue by giving an overview on complement
regulatory molecules. Selected topics included overviews on the
application of C1 inhibitor (C.E. Hack, Amsterdam, NL), sCR1 (U.S.
Ryan, Needham, MA, USA), antibodies to C5 (Y. Wang, New Haven CT,
USA) and to the anaphylatoxin C5a (M. Oppermann, Gottingen, Germany),
and a report on complement inhibition in cardiopulmonary bypass (T.E.
Mollnes, Bodo, Norway). The growing interest of clinicians in
complement-directed anti-inflammatory therapy, and the fact that only
some of the various aspects of therapeutic complement inhibition
could be addressed on the meeting, has motivated the author to expand
a Congress report into a short comprehensive review on recent
strategies to control complement in inflammation.
NLM PUBMED CIT. ID:
9476114
SOURCE: Immunopharmacology 1997 Dec;38(1-2):51-62
20
NLM CIT. ID: 98033561
TITLE: Early onset of acute pulmonary dysfunction after cardiovascular
surgery: risk factors and clinical outcome [see comments]
AUTHORS: Rady MY; Ryan T; Starr NJ
AUTHOR AFFILIATION:
Department of Cardiothoracic Anesthesia, Cleveland Clinic Foundation,
OH, USA.
COMMENTS:
Comment in: Crit Care Med 1997 Nov;25(11):1778-80
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
ABSTRACT:
OBJECTIVE: To define the incidence, risk factors, and clinical outcome
of early pulmonary dysfunction after cardiovascular surgery for
adults. STUDY: Inception cohort. SETTING: Adult cardiovascular
intensive care unit (ICU). PATIENTS: All adult admissions after
cardiovascular surgery without preoperative pulmonary parenchyma or
vascular disease over a period of 12 consecutive months.
INTERVENTION: Collection of data on demographics, preoperative organ
insufficiency, emergency surgery, type of surgical procedure,
cardiopulmonary bypass time, transfusion of blood products,
postoperative arterial blood gases, and systemic hemodynamics on
admission to the cardiovascular ICU. MEASUREMENTS AND MAIN RESULTS:
Early postoperative pulmonary dysfunction was defined by mechanical
ventilation with a PaO2/FIO2 ratio of < or = 150 torr (< or = 20 kPa)
and chest radiography on admission to the cardiovascular ICU.
Secondary outcome included postoperative renal and neurologic
dysfunction, nosocomial infections, length of mechanical ventilation,
hospitalization, and death. A total of 3,122 patients were evaluated
and 1,461 patients satisfied the entry criteria of the study. Early
postoperative pulmonary dysfunction was present in 180 (12%) patients
on admission to the cardiovascular ICU. Preoperative variables: age
of > or = 75 yrs (odds ratio 1.69, 95% confidence interval [CI] 1.06
to 2.65), body mass index of > or = 30 kg/m2 (odds ratio 1.60, 95% CI
1.09 to 2.32), mean pulmonary arterial pressure of > or = 20 mm Hg
(odds ratio 1.60, 95% CI 1.13 to 2.28), stroke volume index of < or =
30 mL/m2 (odds ratio 1.57, 95% CI 1.08 to 2.26), serum albumin (odds
ratio 0.71, 95% CI 0.49 to 0.97), history of cerebral vascular
disease (odds ratio 1.81; 95% CI 1.08 to 2.96); operative variables:
emergency surgery (odds ratio 2.12, 95% CI 1.01 to 4.51), total
cardiopulmonary bypass time of > or = 140 mins (odds ratio 1.54, 95%
CI 1.0 to 2.34); and postoperative variables (on admission to
cardiovascular ICU): hematocrit of > or = 30% (odds ratio 2.46, 95%
CI 1.71 to 3.56), systemic mean arterial pressure of > or = 90 mm Hg
(odds ratio 1.67, 95% CI 1.13 to 2.42), and cardiac index of > or =
3.0 L/min/m2 (odds ratio 2.09, 95% CI 1.44 to 3.01) were predictors
of early postoperative pulmonary dysfunction. Pulmonary dysfunction
was associated with a postoperative increase of serum creatinine
(1.36 +/- 0.4 vs. 1.24 +/- 0.4 mg/dL, p < .02), neurologic
complications (3% vs. 1.6%, p < .001), nosocomial infections (3% vs.
1.6%, p < .001), prolonged mechanical ventilation (2.2 +/- 5.9 vs.
1.7 +/- 5.6 days, p < .001), length of stay in the cardiovascular ICU
(4.4 +/- 12.2 vs. 2.6 +/- 6.2 days, p < .001) and hospital (14.8 +/-
13.1 vs. 10.5 +/- 8.0 days, p < .001), and death (4.4% vs. 1.6%, p <
.001). CONCLUSIONS: The incidence of early postoperative pulmonary
dysfunction is uncommon; however, once developed, it is associated
with increased morbidity and mortality after cardiovascular surgery.
Advanced age, large body mass index, preoperative increased pulmonary
arterial pressure, low stroke volume index, hypoalbuminemia, history
of cerebral vascular disease, emergency surgery, and prolonged
cardiopulmonary bypass time are risk factors for early onset of
severe pulmonary dysfunction after surgery. Postoperative hematocrit
and systemic hemodynamics suggest that early postoperative pulmonary
dysfunction can be a component of a generalized inflammatory reaction
to cardiovascular surgery.
NLM PUBMED CIT. ID:
9366766
SOURCE: Crit Care Med 1997 Nov;25(11):1831-9
21
NLM CIT. ID: 97467784
TITLE: Circulating endotoxin and cytokines after cardiopulmonary bypass:
differential correlation with duration of bypass and systemic
inflammatory response/multiple organ dysfunction syndromes.
AUTHORS: Khabar KS; elBarbary MA; Khouqeer F; Devol E
al-Gain S; al-Halees Z
AUTHOR AFFILIATION:
Department of Biological and Medical Research, King Faisal Specialist
Hospital and Research Center, Riyadh, Saudi Arabia.
khabar@kfshrc.edu.sa
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Cytokines)
0 (Endotoxins)
0 (Interleukin-1)
0 (Interleukin-6)
0 (Interleukin-8)
0 (Lipopolysaccharides)
0 (Tumor Necrosis Factor)
ABSTRACT:
Cardiopulmonary bypass constitutes an injury that may cause
postoperative pathophysiological changes due to systemic inflammatory
response syndrome (SIRS) and multiple organ dysfunction syndrome
(MODS). These complications include coagulopathy, hypotension,
capillary leakage, and multiple organ injury. To investigate the role
of endotoxin and cytokines in the response to bypass injury, we
measured plasma levels of endotoxin and proinflammatory cytokines in
20 pediatric patients before and after bypass. Clinical data,
including duration of injury and tests indicative of SIRS/MODS, were
collected. Levels of endotoxin, TNF-alpha, IL-6, and IL-8 but not
IL-1 beta were significantly increased after bypass. Most of the
cytokines have been found to correlate with each other. Endotoxin did
not correlate with duration of bypass, cytokines, or SIRS/MODS. In
contrast, TNF-alpha and IL-8 correlated with duration of bypass and
were associated with SIRS/MODS. Certain clinical complications were
associated with specific cytokines. Understanding the role of
cytokinemia in SIRS/MODS may lead to better prognostic assessment and
therapeutic modalities.
NLM PUBMED CIT. ID:
9325075
SOURCE: Clin Immunol Immunopathol 1997 Oct;85(1):97-103
22
NLM CIT. ID: 97405450
TITLE: [Cytokines and heart diseases. Attempt at an update]
VERNACULAR TITLE:
Zytokine und Herzkrankheiten. Versuch einer Standortbestimmung.
AUTHORS: Werdan K
AUTHOR AFFILIATION:
Lehrstuhl fur Kardiologische Intensivmedizin an der Klinik fur Innere
Medizin III, Martin-Luther-Universitat Halle-Wittenberg.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Ger
REGISTRY NUMBERS:
0 (Cytokines)
ABSTRACT:
Acute septic cardiomyopathy is-to our present knowledge-the heart
disease most strongly interrelated with cytokines. Myocardial
depression by cytokines is characterized by their pleiotropic actions
mediating not only impairment of one, but several inotropic cascades.
Information concerning the relevance of cytokines in non-septic heart
diseases is-at present-scarce: Concepts emerge in cases of
myocarditis, heart failure and cardiomyopathies, acute coronary
syndromes, systemic inflammatory response due to cardiopulmonary
bypass, heart transplant rejection and Kawasaki disease. CONCLUSION:
Cytokines are involved in heart diseases.
NLM PUBMED CIT. ID:
9324630
SOURCE: Med Klin 1997 Jul 15;92(7):432-8
23
NLM CIT. ID: 97463752
TITLE: The systemic inflammatory response to cardiopulmonary bypass:
pathophysiological, therapeutic, and pharmacological considerations.
AUTHORS: Hall RI; Smith MS; Rocker G
AUTHOR AFFILIATION:
Department of Anaesthesia, Dalhousie University, Halifax, Nova Scotia,
Canada.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Adrenal Cortex Hormones)
0 (Cytokines)
10102-43-9 (Nitric Oxide)
NLM PUBMED CIT. ID:
9322454
SOURCE: Anesth Analg 1997 Oct;85(4):766-82
24
NLM CIT. ID: 98017576
TITLE: Desensitization of the inflammatory response in humans: changes in
response to cardiopulmonary bypass.
AUTHORS: Ng TT; Gibson FA; Nye KE; Hughes PJ; Hinds CJ
Morrow WJ; Ferguson C
AUTHOR AFFILIATION:
Department of Immunology, St. Bartholomew's, London, United Kingdom.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 1.11.1.7 (Peroxidase)
EC 3.4.21.37 (Leukocyte Elastase)
0 (interleukin 8 receptor)
0 (Antigens, CD)
0 (Antigens, CD18)
0 (Cross-Linking Reagents)
0 (Inositol Phosphates)
0 (Interleukin-8)
0 (Receptors, Interleukin)
ABSTRACT:
Although circulating levels of interleukin 8 (IL-8), a potent pro-
inflammatory chemokine, and many other inflammatory mediators
increase in response to cardiopulmonary bypass, only a small
proportion of patients develop a clinically significant systemic
inflammatory response. The natural mechanisms that control the
inflammatory response are poorly understood. To investigate the role
of IL-8 in a human inflammatory model, 15 adult patients undergoing
cardiopulmonary bypass for elective coronary artery bypass grafting
were studied. Following reperfusion, plasma IL-8 levels increased
significantly from 58 pg/mL (pre-bypass) and 66 pg/mL (after 20 min
of bypass) to 98 pg/mL (p = .02 and .04, respectively), but this was
accompanied by a concomitant threefold decrease in the IL-8 binding
affinity of circulating neutrophils (Dissociation constant (KL)
post-reperfusion/KL pre-bypass = 3.2; KL post-reperfusion/KL after 20
min of bypass = 2.8). IL-8- triggered release of myeloperoxidase and
elastase by peripheral blood neutrophils ex vivo was also
down-regulated following reperfusion. There were no significant
changes in beta 2 integrin expression or inositol polyphosphate
metabolism of peripheral blood neutrophils. These changes in receptor
affinity and neutrophil responsiveness to IL- 8 may represent an
important in vivo regulatory mechanism which serves to prevent
excessive tissue injury from inflammatory triggers.
NLM PUBMED CIT. ID:
9377161
SOURCE: Shock 1997 Sep;8(3):159-64
25
NLM CIT. ID: 97441595
TITLE: Increased plasma concentrations of serum amyloid A: an indicator of
the acute-phase response after cardiopulmonary bypass.
AUTHORS: Berendes E; Mollhoff T; Aken HV; Erren M; Deng MC
Loick HM
AUTHOR AFFILIATION:
Department of Anesthesiology and Surgical Intensive Care Medicine,
Institute of Atherosclerosis Research, University of Munster,
Germany.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (amyloid protein AA precursor)
0 (Amyloid Protein AA)
0 (Apolipoproteins)
0 (Endotoxins)
0 (Interleukin-6)
9007-41-4 (C-Reactive Protein)
ABSTRACT:
OBJECTIVES: To assess the expression of mixed and hepatic venous serum
amyloid A (SAA) concentrations and its relationship to plasma
concentrations of C-reactive protein, interleukin-6 (IL-6), and
endotoxin during and after cardiopulmonary bypass (CPB). DESIGN:
Prospective, consecutive sample with repeated measurements. SETTING:
Surgical intensive care unit (ICU) in a university hospital.
PATIENTS: Twenty patients who underwent elective coronary bypass
grafting. INTERVENTIONS: A radial artery catheter, pulmonary artery
catheter, and right hepatic vein catheter were inserted. Blood
samples were collected to determine the different mediators, lactate
concentrations, and oxygen saturations. MEASUREMENTS AND MAIN
RESULTS: After induction of anesthesia, baseline values were obtained
and the following parameters were determined 20 mins after onset of
CPB, 20 mins after termination of CPB, at admission to the ICU, and
6, 8, 12, and 24 hrs later: hemodynamics, body core temperature,
hepatic venous oxygen saturation, and mixed and hepatic venous
lactate, endotoxin, interleukin (IL)-6, C- reactive protein (CRP),
and SAA concentrations. Endotoxin and IL-6 plasma concentrations
increased during CPB, peaked 6 hrs after admission to the ICU
(endotoxin: 23.1 +/- 6.2 pg/mL; IL-6: 646 +/- 104 pg/mL), and
decreased thereafter; SAA and CRP concentrations began to increase
after 6 and 8 hrs, respectively, with the highest concentrations
reached 24 hrs postoperatively (CRP: 14 +/- 3.6 mg/L; SAA: 668 +/-
114 micrograms/mL). Lactate concentrations began to increase 20 mins
after CPB, and continued to increase until 12 hrs postoperatively.
There were no significant differences between mixed and hepatic
venous values of endotoxin, IL-6, CRP, SAA, and lactate (p < .05).
Body core temperature, which was < 37.5 degrees C before surgery for
all patients, increased 6 hrs after admission to the ICU and peaked
12 hrs postoperatively (38.3 +/- 1.1 degrees C). Hepatic venous
oxygen saturation did not change. Correlations were obtained between
IL-6 values and heart rate (r2 = .20; p < .005), and endotoxin
concentrations and systemic vascular resistance (r2 = .18; p < .001).
Body core temperature correlated significantly closer with SAA (r2 =
.52; p < .0001) values than with IL-6 (r2 = .27; p < .0001) or CRP
(r2 = .16; p < .001) values (p < .05). CONCLUSIONS: SAA is an
additional and sensitive marker of the acute-phase response following
CPB; the increase in SAA concentrations parallels the temporary
increase in body core temperature and is preceded by endotoxemia and
IL-6 secretion.
NLM PUBMED CIT. ID:
9295827
SOURCE: Crit Care Med 1997 Sep;25(9):1527-33
26
NLM CIT. ID: 97344348
TITLE: [Systemic inflammatory reactions to extracorporeal therapy measures
(II): Cardiopulmonary bypass]
VERNACULAR TITLE:
Systemische Entzundungsreaktionen extrakorporaler Therapieverfahren
(II): Der kardiopulmonale Bypass.
AUTHORS: Prondzinsky R; Muller-Werdan U; Pilz G; Witthaut R
Stabenow I; Werdan K; Zerkowski HR
AUTHOR AFFILIATION:
Lehrstuhl fur Kardiologische Intensivmedizin,
Martin-Luther-Universitat Halle-Wittenberg, Halle/Saale.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Ger
REGISTRY NUMBERS:
0 (Cytokines)
0 (Receptors, Tumor Necrosis Factor)
0 (Tumor Necrosis Factor)
10102-43-9 (Nitric Oxide)
ABSTRACT:
About 65,000 cardiac patients undergo surgery annually in Germany with
the assistance of cardiopulmonary bypass. The "post pump inflammatory
response" (the systemic and myocardial inflammatory response syndrome
post cardiac surgery), triggered at least in part by the
cardiopulmonary bypass, contributes substantially towards morbidity
(e.g., myocardial depression) and mortality in these patients. The
main mechanisms underlying this inflammatory response are the
complement cascade, the activation of blood cells, the release of
cytokines and the induction to nitric oxide synthesis. The relative
importance of each individual factor, however, is still a matter of
debate. Scoring systems and measurements of tumor necrosis
factor-alpha, as well as soluble tumor necrosis factor receptors,
allow the early detection of an "escalating inflammatory response" in
2-10% of all patients, which is associated with a worse prognosis.
Therapeutic attempts to suppress these systemic and myocardial
inflammatory reactions focus on blockade of the complement system,
coating of CPB membranes with heparin, leucocyte depletion and
attenuation of leucocyte function, elimination of toxins and
mediators by means of hemofiltration, as well as on the
administration of antiproteases, antioxidants, oxygen radical
scavengers and also of immune globulins.
NLM PUBMED CIT. ID:
9265385
SOURCE: Wien Klin Wochenschr 1997 May 23;109(10):346-53
27
NLM CIT. ID: 97305648
TITLE: The influence of cardiopulmonary bypass on cytokines and cell-cell
communication.
AUTHORS: Hill GE; Whitten CW; Landers DF
AUTHOR AFFILIATION:
Department of Anesthesiology, University of Nebraska Medical Center,
Omaha 68198-4455, USA.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
EC 1.14.13.39 (Nitric-Oxide Synthase)
0 (Cytokines)
0 (Endotoxins)
0 (Inflammation Mediators)
0 (Interleukin-1)
0 (Interleukin-6)
0 (Tumor Necrosis Factor)
ABSTRACT:
Cardiopulmonary bypass (CPB) is characterized by systemic endotoxemia
immediately after its onset as well as the systemic release of
proinflammatory cytokines, including tumor necrosis factor-alpha and
the interleukins 1 and 6. Recent studies document that increased
morbidity and mortality rates correlate with elevated systemic
concentrations of these proinflammatory cytokines during adult and
neonatal sepsis, following thoracoabdominal aortic aneurysm repair,
as well as following CPB. These proinflammatory cytokines induce
increased neutrophil and endothelial surface adhesive molecule
expression, thereby promoting enhanced neutrophil-endothelial
adherence. Increased neutrophil-endothelial adherence and subsequent
neutrophil organ binding are thought to be a "final common pathway"
of organ injury during clinical inflammatory conditions.
Proinflammatory cytokines also increase cellular expression of
inducible nitric oxide synthase, thus increasing cellular production
of nitric oxide, a known inflammatory mediator. This review discusses
recent evidence of the adverse effects of proinflammatory cytokine
release during CPB and therapeutic modalities that can reduce the
systemic concentrations of these mediators of inflammation.
NLM PUBMED CIT. ID:
9161906
SOURCE: J Cardiothorac Vasc Anesth 1997 May;11(3):367-75
28
NLM CIT. ID: 97286822
TITLE: Effects of dopexamine on creatinine clearance, systemic inflammation,
and splanchnic oxygenation in patients undergoing coronary artery
bypass grafting.
AUTHORS: Berendes E; Mollhoff T; Van Aken H; Schmidt C
Erren M; Deng MC; Weyand M; Loick HM
AUTHOR AFFILIATION:
Department of Anesthesiology and Intensive Care Medicine, University
of Munster, Germany.
PUBLICATION TYPES:
CLINICAL TRIAL
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Adrenergic beta-Agonists)
0 (Amyloid Protein AA)
0 (Endotoxins)
0 (Interleukin-6)
50-21-5 (Lactic Acid)
51-61-6 (Dopamine)
60-27-5 (Creatinine)
7782-44-7 (Oxygen)
86197-47-9 (dopexamine)
9007-41-4 (C-Reactive Protein)
ABSTRACT:
Impairment of splanchnic and peripheral tissue perfusion during
cardiopulmonary bypass (CPB) may be responsible for
endotoxin-mediated systemic inflammation and acute phase responses.
We examined the effects of dopexamine on hemodynamic parameters,
creatinine clearance, systemic and splanchnic oxygenation, gastric
mucosal pH (pHi), and mixed and hepatic venous plasma levels of
endotoxin, interleukin-6 (IL- 6), serum amyloid A (SAA), and
C-reactive protein (CRP) in 44 patients scheduled for coronary artery
bypass grafting. Patients were randomized to receive continuous
infusions of 0.5, 1.0, or 2 micrograms.kg-1.min-1 dopexamine (n = 10
per group) or placebo (n = 14) prior to surgery, intraoperatively,
and postoperatively. Dopexamine infusion increased systemic oxygen
delivery (P < or = 0.01). Hepatic venous oxygen saturation did not
change, and pHi decreased during and after CPB in all patients (P <
or = 0.01). Postoperative increases in IL-6 were smallest in patients
who received 2.0 micrograms.kg-1.min-1 dopexamine (P < or = 0.02).
SAA and CRP increases during the postoperative period were less
pronounced with dopexamine throughout the study. Creatinine clearance
was elevated in all dopexamine groups (P < or = 0.025). This
elevation was higher with lower dopexamine doses (P < or = 0.025). We
conclude that dopexamine improves creatinine clearance and reduces
systemic inflammation without affecting splanchnic oxygenation.
NLM PUBMED CIT. ID:
9141914
SOURCE: Anesth Analg 1997 May;84(5):950-7
29
NLM CIT. ID: 97295408
TITLE: Plasma levels of immunoinhibitory cytokines interleukin-10 and
transforming growth factor-beta in patients undergoing coronary
artery bypass grafting.
AUTHORS: Sablotzki A; Welters I; Lehmann N; Menges T
Gorlach G; Dehne M; Hempelmann G
AUTHOR AFFILIATION:
Department of Anaesthesia and Intensive Care Medicine, Justus-Liebig-
University, Giessen, Germany.
PUBLICATION TYPES:
JOURNAL ARTICLE
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Transforming Growth Factor beta)
130068-27-8 (Interleukin-10)
ABSTRACT:
OBJECTIVE: Cardiovascular surgery with extracorporeal circulation
causes a systemic inflammatory response, which can lead to organ
failure and increased postoperative morbidity. Advances in knowledge
about the interactions between markers of cellular and humoral
immunity involved in the inflammatory response to cardiopulmonary
bypass (CPB) may reduce the deleterious effects and improve the
outcome for patients undergoing cardiac surgery. METHODS: To
determine the release of immunoinhibiting cytokines during CPB, we
measured plasma levels of interleukin-10 (IL-10) and transforming
growth factor-beta (TGF-beta) in 30 patients undergoing elective
coronary artery bypass grafting. Arterial blood samples were
collected at eight time points before, during and after CPB, using a
standardized ELISA-technique. RESULTS: Plasma IL-10 and TGF-beta
increased significantly after weaning off CPB (P < 0.05) and peaked
respectively at time of skin closure (IL-10, 308 +/- 180 pg/ml;
TGF-beta, 1860 +/- 906 pg/ml; mean peak +/-S.D.). Postoperatively, 6
h, IL-10 decreased to 19.8 +/- 9.8 pg/ml (P < 0.05) and TGF-beta
decreased to 1133 +/- 547 pg/ml (P < 0.05). CONCLUSIONS: Both
cytokines are major immunoregulatory factors with negative influence
on T cell-mediated immunologic response. The significantly elevated
levels at the end of CPB indicate that IL-10 and TGF-beta may be
important factors of immunologic dysregulation following CPB.
NLM PUBMED CIT. ID:
9151050
SOURCE: Eur J Cardiothorac Surg 1997 Apr;11(4):763-8
30
NLM CIT. ID: 97146436
TITLE: Endothelial cell injury in cardiovascular surgery: the systemic
inflammatory response.
AUTHORS: Boyle EM Jr; Pohlman TH; Johnson MC; Verrier ED
AUTHOR AFFILIATION:
Division of Cardiothoracic Surgery, University of Washington, Seattle,
USA.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Cell Adhesion Molecules)
ABSTRACT:
Many of the components currently used to perform cardiovascular
operations lead to systemic insults that result from cardiopulmonary
bypass circuit-induced contact activation, circulatory shock, and
resuscitation, and a syndrome similar to endotoxemia. Experimental
observations have demonstrated that these events have profound
effects on activating endothelial cells to recruit neutrophils from
the circulation. Once adherent to the endothelium, neutrophils
release cytotoxic proteases and oxygen-derived free radicals, which
are responsible for much of the end-organ damage seen after
cardiovascular operations. Recently the cellular and molecular
mechanisms of endothelial cell activation have become increasingly
understood. It is conceivable that once the molecular mechanisms of
endothelial cell activation are better defined, therapies will be
developed allowing the selective or collective inhibition of vascular
endothelial activation during the perioperative period.
NLM PUBMED CIT. ID:
8993292
SOURCE: Ann Thorac Surg 1997 Jan;63(1):277-84
31
NLM CIT. ID: 97146435
TITLE: Cytokine responses to cardiopulmonary bypass: lessons learned from
cardiac transplantation.
AUTHORS: Wan S; LeClerc JL; Vincent JL
AUTHOR AFFILIATION:
Department of Cardiac Surgery, University Hospital Erasme, Free
University of Brussels, Belgium.
PUBLICATION TYPES:
JOURNAL ARTICLE
REVIEW
REVIEW, TUTORIAL
LANGUAGES:
Eng
REGISTRY NUMBERS:
0 (Adrenal Cortex Hormones)
0 (Cytokines)
130068-27-8 (Interleukin-10)
ABSTRACT:
BACKGROUND: A growing body of evidence relates the release during
cardiopulmonary bypass (CPB) of proinflammatory cytokines, such as
tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, to the
postoperative systemic inflammatory response syndrome.
Antiinflammatory cytokines, such as IL-10, however, may also play an
important role in limiting these complications. METHODS: The
English-language literature was reviewed. Emphasis was placed on
cytokine responses during clinical CPB for cardiac operations and, in
particular, for heart and heart-lung transplantation. RESULTS: The
recent data indicate that (1) although cytokine release can be
triggered by many factors during CPB, ischemia- reperfusion may play
the most important role; (2) the levels of tumor necrosis
factor-alpha, IL-6, and IL-8 are correlated with the duration of
cardiac ischemia and the myocardium is a major source of these three
cytokines during CPB; (3) IL-10 levels are correlated with the
duration of CPB and the liver is a major source of IL-10 during CPB;
and (4) steroid pretreatment is an effective intervention to inhibit
the release of proinflammatory cytokines and enhance IL-10
production. CONCLUSIONS: The improved knowledge of cytokine responses
to CPB may help to develop interventions aimed at reducing
postoperative morbidity and mortality.
NLM PUBMED CIT. ID:
8993291
SOURCE: Ann Thorac Surg 1997 Jan;63(1):269-76
Last Updated: Saturday, June 7, 2003
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