Chin Med J (Engl). 2003 Oct;116(10):1504-7.  

Combination of balanced ultrafiltration with modified ultrafiltration
attenu-ates pulmonary injury in patients undergoing open heart surgery.

Huang H, Yao T, Wang W, Zhu D, Zhang W, Chen H, Fu W.

Department of Thoracocardiac Surgery, Children's Medical Center, Xinhua
Hospital, Shanghai Second Medical University, Shanghai 200127, China (Email:
wenfeik@online.sh.cn)

OBJECTIVE: To explore the effects of ultrafiltration technique in preventing and
relieving pulmonary injury in children undergoing open heart surgery and
cardiopulmonary bypass (CPB). METHODS: Thirty cases with congenital heart
defects were divided into a control group and an experimental group. In the
control group, conventional cardiopulmonary bypass was used without
ultrafiltration; while in the experimental group, cardiopulmonary bypass with
balanced ultrafiltration and modified ultrafiltration were used. Pulmonary
static compliance (Cstat), airway resistance (Raw), alveolar-arterial oxygen
difference (A-a DO2), hematocrit (HCT), serum albumin (Alb), interleukin-6
(IL-6), endothelia-1 (ET-1) and thromboxane (TXB2) were measured. RESULTS: The
pulmonary function was improved, HCT and serum albumin concentrations were
increased, and some harmful medium-size solutes were decreased in the
experimental groups compared with the control group. CONCLUSIONS: Combination of
balanced ultrafiltration with modified ultrafiltration can effectively
concentrate blood, exclude harmful inflammatory mediators, and attenuate lung
edema and inflammatory responsive pulmonary injury.

J Thorac Cardiovasc Surg. 2003 Oct;126(4):1061-4.  

Postoperative hypoxia is a contributory factor to cognitive impairment after
cardiac surgery.

Browne SM, Halligan PW, Wade DT, Taggart DP.

OBJECTIVE: Cognitive dysfunction and postoperative hypoxia are common sequelae
of coronary artery bypass grafting, but there has been no study to determine
whether there is any relationship between them. METHODS: Arterial blood gas
measurements were performed before surgical intervention and on the second and
fifth postoperative day, and neuropsychological assessments were performed
before surgical intervention and 5 days and 3 months postoperatively by using a
battery of 10 psychometric tests in 175 patients undergoing coronary artery
bypass grafting. An estimate of overall performance on the battery at each
assessment point was provided by a simple aggregate cognitive index score
calculated from the mean z scores of 4 normally distributed test variables.
Multiple regression analysis was performed by using the cognitive index score at
day 5 as the dependent variable, with age, sex, duration of the operation,
presence or absence of cardiopulmonary bypass, preoperative cognitive index
score, and arterial oxygenation and percentage of saturation at day 5 as
independent variables. RESULTS: The mean cognitive index score decreased
significantly in 115 (66%) patients who agreed to neuropsychological test
battery assessment on the fifth postoperative day but improved significantly
beyond baseline at 3 months. Mean arterial oxygen tension and percentage of
saturation decreased significantly 2 days after the operation and, although
improving over the following 3 days, remained decreased at day 5. Decreased
cognitive index scores at day 5 strongly predicted cognitive impairment at 3
months (r = 0.36). The only significant independent predictors of the day 5
cognitive index score in the multiple regression analysis were preoperative
cognitive index score and arterial oxygenation tension at day 5 (r = 0.24, P
<.03). CONCLUSIONS: We report a significant correlation between postoperative
cognitive dysfunction and hypoxia 5 days after coronary artery bypass grafting.
This finding might have therapeutic implications because early postoperative
cognitive dysfunction influences long-term impairment.

Am J Physiol Heart Circ Physiol. 2003 Oct 16 [Epub ahead of print].  

Effect of Bronchial Artery Blood Flow on Cardiopulmonary Bypass-Induced Lung
Injury.

Dodd-O JM, Welsh LE, Salazar JD, Walinsky PL, Peck EA, Shake JG, Caparrelli DJ,
Bethea BT, Cattaneo SM, Baumgartner WA, Pearse DB.

Department of Anesthesia and Critical Care, Johns Hopkins University, Baltimore,
MD, USA.

Cardiovascular surgery requiring cardiopulmonary bypass (CPB) is frequently
complicated by postoperative lung injury. Bronchial artery (BA) blood flow has
been hypothesized to attenuate this injury. The purpose of this study was to
determine the effect of BA blood flow on CPB-induced lung injury in anesthetized
pigs. In 8 pigs (BA-ligated), the BA was ligated whereas in 6 pigs (BA-patent),
the BA was identified but left intact. Warm (37 degrees C) CPB was then
performed in all pigs with complete occlusion of the pulmonary artery and
deflated lungs to maximize lung injury. Bronchial artery ligation significantly
exacerbated nearly all aspects of pulmonary function beginning at 5 min
post-CPB. At 25 min, BA-ligated pigs had a lower PaO2 on FIO2 of 1.0 (52 +/- 5
vs. 312 +/- 58 mmHg), and greater peak tracheal pressure (39 +/- 6 vs. 15 +/- 4
mmHg), pulmonary vascular resistance (11 +/- 1 vs. 6+/- 1 mmHg(.)L(-1) (.)min),
plasma TNF-alpha (1.2 +/- 0.60 vs. 0.59 +/- 0.092 ng(.)ml(-1)), extravascular
lung water (11.7 +/- 1.2 vs. 7.7 +/- 0.5 ml(.)g(-1) blood-free dry weight) and
pulmonary vascular protein permeability as assessed by a decreased reflection
coefficient for albumin (sigmaalb; 0.53+/- 0.1 vs. 0.82 +/- 0.05). There was a
negative correlation (R=0.95, P<0.001) between sigmaalb the 25 min plasma
TNF-alpha concentration. These results suggest that a severe decrease in BA
blood flow during and after warm CPB causes increased pulmonary vascular
permeability, edema formation, cytokine production, and severe arterial
hypoxemia secondary to intrapulmonary shunt.

J Surg Res. 2003 Oct;114(2):254.  

Complement does not mediate the cardiac inflammatory response initiated by
myocardial ischemia-reperfusion during cardiopulmonary bypass.

Roshanravan B, Fullerton DA, Blum MG.

Northwestern University Medical School, USA

INTRODUCTION: This study was designed to test the hypothesis that complement
mediates the cardiac inflammatory response resulting from ischemia during
cardiopulmonary bypass (CPB). METHODS: Paired aortic and coronary sinus blood
samples were collected from patients undergoing elective, first-time coronary
bypass grafting with CPB (n = 17). Sera was analyzed using ELISA to detect
levels of C3a and C5a. Histamine, as a marker of C3a or C5a stimulation of the
inflammatory response, was also measured. Atrial tissue samples were collected
before and after CPB. Tissue was immunohistochemically stained for alternative
and classical complement pathway proteins C1q and factor Bb. RESULTS: Systemic
C3a levels increased during CPB (837 +/- 599 ng/ml). Histamine, C3a and C5a
levels across the heart (coronary sinus minus aortic values) were not
significantly different at any time-point (baseline: 0.27 +/- 1.45, 29 +/- 82,
-0.45 +/- 2.5; reperfusion: -0.35 +/- 0.42, -55 +/- 211, 0.25 +/- 1.20 for
histamine, C3a and C5a respectively). Immunohistochemical stains showed no
deposition of C1q or Factor Bb. CONCLUSIONS: The myocardium is not a source of
the complement activation seen during the ischemia-reperfusion of CPB. The
elevated levels of C3a created during CPB does not stimulate cardiac
inflammation. Complement does not play a significant role in post-CPB cardiac
inflammatory state.

Paediatr Anaesth. 2003 Oct;13(8):655-661.  

Chemokines and the inflammatory response following cardiopulmonary bypass - a
new target for therapeutic intervention? - a review.

Ben-Abraham R, Weinbroum AA, Dekel B, Paret G.

Departments of Anesthesiology and Critical Care Medicine, Tel-Aviv Sourasky
Medical Center Pediatric Intensive Care, Chaim Sheba Medical Center, Tel
Hashomer, affiliated to the Sackler Faculty of Medicine, Tel Aviv University,
Tel Aviv Weizmann Institute of Science, Department of Immunology, Rehovot,
Israel.

This 10-year Medline search of English-language articles describing experimental
and clinical studies on chemokines, cardiopulmonary bypass (CPB) and systemic or
multiorgan failure revealed that chemokines are significantly involved in the
pathogenesis of post-CPB syndrome. The post-CPB inflammatory response depends
upon recruitment and activation of inflammatory cells. Leucocyte recruitment is
a well-orchestrated process that involves several protein families, including
pro-inflammatory cytokines, adhesion molecules and chemokines. Current
anti-inflammatory therapies mostly act on the cells that have already been
recruited. A more efficient therapy might be the prevention of excessive
recruitment of particular leucocyte populations by antagonizing chemokine
receptors which might act upstream of the current anti-inflammatory agents. The
chemokines, which are a cytokine subfamily of chemotactic cytokines, participate
in recognizing, recruiting, removing and repairing inflammation. As chemokines
target specific leucocyte subsets, antagonism of a single chemokine ligand or
receptor would be expected to have a circumscribed effect, thereby endowing the
antagonist with a limited side-effect profile. Chemokines should be considered
as possible targets for therapeutic intervention.

Ann Thorac Surg. 2003 Oct;76(4):1227-33; discussion 1233.  

Myocardial protection with intermittent cold blood during aortic valve
operation: antegrade versus retrograde delivery.

Lotto AA, Ascione R, Caputo M, Bryan AJ, Angelini GD, Suleiman MS.

Bristol Heart Institute, University of Bristol, Bristol, United Kingdom.

BACKGROUND: Intermittent antegrade cold blood cardioplegia is superior to warm
blood cardioplegia in patients who have aortic valve operation. This study
compared the cardioprotective efficacy of intermittent antegrade and retrograde
cold blood cardioplegia with emphasis on metabolic stress in the left and right
ventricles. METHODS: Thirty-nine patients who had elective aortic valve
replacement were prospectively randomly selected to receive intermittent
antegrade or retrograde cold blood cardioplegia. Left and right ventricular
biopsies were collected 5 minutes after institution of cardiopulmonary bypass
and 20 minutes after cross-clamp removal and were used to determine metabolic
changes. Metabolites (adenine nucleotides, amino acids, and lactate) were
measured using high-powered liquid chromatography and enzymatic techniques.
Serial measurement of troponin I release was also used as a marker of myocardial
injury. RESULTS: Preoperative characteristics were similar between groups. There
was no in-hospital mortality, and no differences were observed in postoperative
complications. Preischemic concentration of taurine was significantly higher in
left ventricular biopsies, whereas adenosine triphosphate tended to be lower in
the left ventricle. At reperfusion adenosine triphosphate levels were
significantly lower than preischemic levels in right but not left ventricles
irrespective of the route of delivery. The alanine-glutamate ratio was
significantly elevated in both ventricles. Myocardial injury as assessed by
troponin I release was also significantly increased in both groups. CONCLUSIONS:
Retrograde and antegrade intermittent cold blood cardioplegic techniques are
associated with suboptimal myocardial protection. Metabolic stress was more
pronounced in the right than the left ventricle irrespective of the cardioplegic
route of delivery used.

Ann Thorac Surg. 2003 Oct;76(4):1144-8; discussion 1148.  

Heparin-coated circuits and reduced systemic anticoagulation applied to 2500
consecutive first-time coronary artery bypass grafting procedures.

Ovrum E, Tangen G, Tollofsrud S, Ringdal MA.

Oslo Heart Center, Oslo, Norway. eivind.ovrum@hjertesenteret.no

BACKGROUND: In contrast to the widespread popularity of off-pump techniques for
coronary artery bypass grafting, our institution has chosen a different
strategy, emphasizing improvements in the technology for extracorporeal
circulation, as well as simplifying surgical and clinical management. The
clinical short-term results of this approach were analyzed. METHODS: The on-pump
strategy includes routine use of heparin-coated circuits combined with low
systemic heparinization (activated coagulation time of more than 250 seconds),
intention of total revascularization within limited ischemic times and pump
times, minimal use of blood transfusions, early extubation, and rapid
postoperative recovery. The data from the first 2,500 consecutive first-time
coronary artery bypass grafting patients (January 1998 to February 2002) treated
with this protocol were retrospectively analyzed. RESULTS: There were 487 female
(median age 68 years) and 2013 male (median age 64 years) patients. A median of
four (one to nine) (mean 4.5 +/- 1.2) distal anastomoses were created, and the
median aortic cross-clamp time and pump time were 34 and 54 minutes,
respectively. At least one internal mammary artery was used in 99.7% of the
patients. Blood or bank blood products were given to 118 patients (4.7%). Median
extubation time was 1.5 hours. The stroke rate was 0.8%, transient neurologic
deficits occurred in 0.6% of the patients, and the incidence of perioperative
myocardial infarction was 1.1%. By the fifth day, 91% of the patients were ready
for discharge. Seven patients (0.28%) died during their hospital stay.
CONCLUSIONS: Coronary artery bypass grafting with heparin-coated cardiopulmonary
bypass circuits and reduced systemic anticoagulation resulted in excellent
clinical results, with minimal blood transfusions and rapid postoperative
mobilization. The high number of grafted coronary arteries indicates complete
revascularization in most patients, which is known to be a significant predictor
of long-term event-free survival.

Eur J Cardiothorac Surg. 2003 Oct;24(4):557-70.  

Off-pump coronary artery bypass grafting: the myth, the logic and the science.

Ngaage DL.

Department of Cardiothoracic Surgery, Yorkshire Heart Centre, Leeds General
Infirmary, Great George Street, Leeds LS1 3EX, West Yorkshire, UK.
ngaage.dumbor@mayo.edu

Coronary artery bypass grafting is a highly investigated surgical procedure and
yet continues to attract rigorous research aimed at reducing observed and
potential morbidity and mortality. Improvements in perioperative care, surgical
technique and methods of attenuating the untoward effects of cardiopulmonary
bypass have resulted in improved clinical outcome of on-pump myocardial
revascularisation. The continuing drive to improve clinical outcome and compete
with the ever-evolving non-surgical methods of myocardial revascularisation has
provided the incentive for the rebirth of off-pump coronary artery bypass
grafting (OPCAB). The appeal of avoiding cardiopulmonary pass with its direct
and indirect physiological insult, the prospect of improved clinical outcomes,
and the favourable economic impact gives OPCAB the potential of preference that
may mark the dawn of a new era in our search for the optimal surgical strategy
for the treatment of coronary artery disease. However, there are very genuine
and serious concerns with this surgical technique. The logical appeal of OPCAB
can only be validated by scientific scrutiny otherwise it would remain a
myth.This comprehensive review examines the "physiological cost" of
cardiopulmonary bypass, the theoretical and clinical benefits of OPCAB, the
concerns with this technique and strategies for maximizing the benefits. And in
so doing, explore the myth, the logic and the science of this surgical
technique.

World J Surg. 2003 Oct;27(10):1093-8. Epub 2003 Aug 21. 

Relation of cytokines to vasodilation after coronary artery bypass grafting.

Wei M, Kuukasjarvi P, Laurikka J, Kaukinen S, Honkonen EL, Metsanoja R, Tarkka
M.

Division of Cardiovascular Surgery, University of Tampere, PO Box 2000,
Fin-33521 Tampere, Finland.

Hemodynamic instability is frequent after coronary surgery. The present study
tested the hypothesis that inflammation, as determined by circulating cytokine
levels, may contribute to the difficulty of controlling arterial blood pressure
after coronary artery bypass grafting. A group of 44 male patients undergoing
elective coronary artery bypass grafting with cardiopulmonary bypass were
studied. Plasma levels of tumor necrosis factor-alpha, interleukin-6 (IL-6),
IL-8, and IL-10 were measured before anesthesia induction, 5 minutes and 1 hour
after reperfusion to the myocardium, and 2 and 18 hours after arriving in the
intensive care unit (ICU). The 29 patients who did not need a vasopressor
(norepinephrine) during their ICU stay were designated group I. They were
compared to group II, which consisted of 15 patients who required a pressor
agent in the ICU. Although no significant differences between groups were found
regarding their hemodynamic variables, IL-6 and IL-8 levels were higher in the
patients who used a pressor agent in the ICU. The norepinephrine dosage used in
the ICU correlated with plasma IL-8 levels 2 hours after arriving in the ICU (r
= 0.56, p = 0.031). Circulating IL-6 levels in group II were significantly
higher than those in group I 2 hours after arriving in the ICU (126.5 +/- 90.5
vs. 66.5 +/- 48.2 pg/ml; p < 0.05). The mean IL-8 levels were higher in group II
at 5 minutes (34.9 +/- 25.7 vs. 17.3 +/- 11.3 pg/ml) and 1 hour (38.6 +/- 30.5
vs. 22.4 +/- 16.7 pg/ml) after reperfusion, and 2 hours (33.0 +/- 21.6 vs. 22.8
+/- 16.7 pg/ml) after arriving in the ICU (p = 0.036). Postoperative
vasodilation was associated with increased circulating IL-8 levels. Strategies
that modulate cytokine responses may improve hemodynamic stability after
coronary artery bypass grafting.