Clin Cardiol. 2006 Jul;29(7):311-5. 

Effect of cardiopulmonary bypass on cytokine network and myocardial cytokine
production.

Gasz B, Lenard L, Racz B, Benko L, Borsiczky B, Cserepes B, Gal J, Jancso G,
Lantos J, Ghosh S, Szabados S, Papp L, Alotti N, Roth E.

Department of Surgical Research and Techniques, University of Pecs, Hungary.
balazs.gasz@aok.pte.hu

BACKGROUND: In addition to the well-investigated proinflammatory cytokine
expression, there is an ever increasing interest in the field of
anti-inflammatory response to cardiopulmonary bypass (CPB). Evidence suggests
that myocardium serves as an important source of cytokines during reperfusion
and application of CPB. The effect of coronary artery bypass graft (CABG)
without CPB on myocardial cytokine production has not as yet been investigated.
HYPOTHESIS: Cardiopulmonary bypass can cause long-term disturbance in pro- and
anti-inflammatory cytokine balance, which may impede a patient's recovery
following surgery. Therefore, the effect of CPB on the balance of the
pro-/anti-inflammatory cytokines network and myocardial cytokine outflow was
assessed throughout a longer period after surgery. METHODS: Twenty patients were
scheduled for CABG with CPB and 10 had off-pump surgery. Blood samples were
taken before, during, and over the first week following surgery. Coronary sinus
blood samples were collected during surgery. The ratio of pro- and
anti-inflammatory cytokines was calculated and the cytokine concentration of
peripheral and coronary sinus blood were compared in both groups. RESULTS:
Pro-/anti-inflammatory cytokine ratio decreased early after CPB followed by a
delayed and marked increase. A more balanced ratio was present following
off-pump surgery. Coronary sinus levels of certain cytokines exceeded the
concentration of systemic blood in the course of CPB but not during off-pump
operation. CONCLUSION: Patients show pro-inflammatory predominant cytokine
balance at a later stage after CPB in contrast to those without CPB. The heart
produces a remarkable amount of cytokines only in the course of surgery with
CPB.

Heart Lung Circ. 2006 Jul 20; [Epub ahead of print] 

Does Off-pump Coronary Revascularization Reduce the Release of the Cerebral
Markers, S-100beta and NSE?

Bonacchi M, Prifti E, Maiani M, Bartolozzi F, Di Eusanio M, Leacche M.

Cardiac Surgery Department, Policlinico Careggi, Firenze, Italy.

OBJECTIVES: The aims of this study were to (1) compare the release of S-100beta
and NSE in off-pump coronary artery bypass grafting (CABG) versus on-pump
surgery; (2) investigate whether the S-100beta and NSE serum concentrations
correlate with cardiopulmonary bypass (CPB) duration. MATERIALS AND METHODS:
Between October 2002 and May 2004, 42 patients undergoing first time CABG
surgery were enrolled in the study. The exclusion criteria were: LVEF<35%,
age>70 years, previous myocardial infarction, REDO surgery, the presence of
valvular heart disease and/or cerebrovascular disease, abnormal preoperative
carotid vessels angiography, coronary artery disease involving the distal
circumflex artery, renal dysfunction, coagulopathy. The patients were randomly
assigned either to undergo on-pump CABG surgery [group I, n=24 patients] or
off-pump CABG [group II, n=18 patients]. Blood was not re-transfused from the
cardiotomy suction. All patients presenting haemolysis were excluded from the
study. RESULTS: The preoperative S-100beta was 0.13+/-0.08 (mug/l) and NSE
7+/-1.5 (mug/l) in group I and 0.12+/-0.1 (mug/l) and 6.9+/-2.7 (mug/l),
respectively in group II. Six hours after the surgery, S-100beta in patients of
group I reached a maximum level of 1.38+/-0.4 (mug/l) and NSE of 17.7+/-6.5
(mug/l) compared to 0.5+/-0.11 (mug/l) [S-100B] and NSE 8.6+/-4.2 (mug/l) in
group II (p=0.001). Three (12%) patients in group I and none (0%) in group II
suffered postoperative delirium, p=0.247. No strokes occurred linear regression
analysis revealed a strong correlation between cardiopulmonary bypass duration
and S-100beta and NSE peak levels, p<0.0021 (r(2)=0.36) and p<0.0001 (r=0.81),
respectively. CONCLUSION: Coronary artery bypass surgery with CPB causes a
significantly greater increase in NSE and S-100beta serum levels than off-pump
surgery and correlates with CPB duration.

Eur J Cardiothorac Surg. 2006 Jul 18; [Epub ahead of print] 

Risk factors of postoperative nephropathy in patients undergoing innovative CABG
and intraoperative graft angiography.

Schachner T, Bonatti J, Bonaros N, Poeltl R, Feuchtner G, Laufer G, Pachinger O,
Friedrich G.

Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.

Introduction: Intraoperative graft angiography is considered gold standard in
quality control of innovative CABG techniques. Iodixanol, an iso-osmolar,
non-ionic contrast agent has been safely applied in patients with impaired renal
function. We aimed to quantify postoperative nephropathy in CABG patients
undergoing intraoperative angiography and to define associated risk factors.
Methods: One hundred and thirty-five patients, aged 61 years (range: 43-83),
underwent intraoperative angiography following CABG (36 robotically assisted
CABG via sternotomy, 41 OPCAB and MIDCAB, 51 AHTECAB, 7 BHTECAB). In all
patients iodixanol (Visipaquetrade mark) was used, median amount: 150ml (range:
20-500). Nephropathy was defined as an increase in serum creatinine
concentration >/=0.5mg/dl compared with preoperative values. Results:
Nephropathy occured in 19/135 (14%) patients, and was correlated with the
following variables: preoperative serum creatinine (p=0.015, r=0.208), age
(p=0.008, r=0.229), postoperative peak troponin T levels (p<0.001, r=0.545),
postoperative CK-MB peak levels (p=0.028, r=0.189), and presence of peripheral
vascular disease (p=0.011). No correlation was found for the contrast agent
amount, diabetes mellitus, hypertension, preoperative urea level,
cardiopulmonary bypass time, aortic cross clamp time, postoperative CK peak
levels. Multivariate analysis showed that postoperative peak troponin T levels
(p<0.001), preoperative serum creatinine (p=0.031), and patient age (p=0.043)
were independently associated with a postoperative increase of serum creatinine.
In all 19 patients with postoperative nephropathy serum creatinine levels
returned to preoperative levels. Conclusion: Patients with older age and
elevated serum creatinine levels undergoing innovative CABG and intraoperative
angiography were at increased risk of postoperative nephropathy. However, no
correlation was found between the amount of contrast agent (iodixanol) applied
and the nephropathy rate and none of the nephropathy cases persisted.

J Biomed Mater Res B Appl Biomater. 2006 Jul 18; [Epub ahead of print] 

Effect of biopassive and bioactive surface-coatings on the hemocompatibility of
membrane oxygenators.

Zimmermann AK, Weber N, Aebert H, Ziemer G, Wendel HP.

Department of Thoracic, Cardiac, and Vascular Surgery, University Hospital,
Eberhard-Karls-University, Tuebingen, Germany.

Postoperative complications associated with cardiopulmonary bypass (CPB) surgery
and extracorporeal circulation (ECC) procedures are still a major clinical
issue. Improving the hemocompatibility of blood contacting devices used for ECC
procedures may ameliorate various postpump syndromes. In a simulated CPB model
using human blood, we investigated the hemocompatibility, fibrinogen adsorption,
and platelet receptor (GPIIb-IIIa) binding capacity of surface-modified membrane
oxygenators (Jostra Quadrox). Three groups were compared: (i) biopassive protein
coatings (SafeLine(R)), (ii) bioactive heparin coatings (BioLine(R)), and (iii)
noncoated controls. During the 2 h recirculation period, plasma concentrations
of activation markers for platelets (beta-thromboglobulin), inflammation
(elastase), complement (C5a), and coagulation (prothrombin fragment 1+2,
thrombin-antithrombin III) were lower in the groups with biopassive and
bioactive coatings compared to the noncoated group (p < 0.01). These parameters
did not significantly differ between the two surface-coated groups, except for
complement activation: C5a levels were higher in the biopassive group compared
to the bioactive group (p < 0.01). Moreover, surface-coated oxygenators showed
less fibrinogen adsorption, GPIIb-IIIa binding, and platelet/leukocyte adhesion
(p < 0.01). We assume that fewer fibrinogen and platelet receptor molecules
bound to the surface-coated oxygenator surfaces results in fewer platelet
adhesion and activation, which will significantly contribute to the improved
hemocompatibility of the biopassive and bioactive oxygenators. Our results
suggest that the application of bioactive oxygenators (BioLine(R)) during CPB
surgery may reduce postoperative complications for the patient more effectively
than biopassive oxygenators (SafeLine(R)). 

J Thromb Haemost. 2006 Jul;4(7):1523-9. 

Thrombin generation during reperfusion after coronary artery bypass surgery
associates with postoperative myocardial damage.

Raivio P, Kuitunen A, Suojaranta-Ylinen R, Lassila R, Petaja J.

Department of Cardiothoracic Surgery, Helsinki University Central Hospital,
FIN-00029 HUS, Helsinki, Finland. peter.raivio@hus.fi

BACKGROUND: Cardiopulmonary bypass and coronary artery bypass grafting (CABG)
result in significant thrombin generation and activation of fibrinolysis.
Thrombin contributes to myocardial ischemia-reperfusion injury in animal
studies, but the role of thrombin in myocardial damage after CABG is unknown.
OBJECTIVES: We measured thrombin generation and fibrin turnover during
reperfusion after CABG to evaluate their associations with postoperative
hemodynamic changes and myocardial damage. METHODS: One hundred patients
undergoing primary, elective, on-pump CABG were prospectively enrolled. Plasma
prothrombin fragment F(1+2) and D-dimer were measured preoperatively and at
seven time points thereafter. Mass of the Mb fraction of creatine kinase
(Ck-Mbm) and troponin T (TnT) were measured on the first postoperative day.
RESULTS: Reperfusion induced an escalation of thrombin generation and fibrin
turnover despite full heparinization. F(1+2) during early reperfusion associated
with postoperative pulmonary vascular resistance index. F(1+2) at 6 h after
protamine administration correlated with Ck-Mbm (r = 0.40, P < 0.001) and TnT (r
= 0.44, P < 0.001) at 18 h postoperatively. Patients with evidence of myocardial
damage (highest quintiles of plasma Ck-Mbm and TnT) had significantly higher
F(1+2) during reperfusion than others (P < 0.002). Logistic regression models
identified F(1+2) during reperfusion to independently associate with
postoperative myocardial damage (odds ratios 2.5-4.4, 95% confidence intervals
1.04-15.7). CONCLUSIONS: Reperfusion caused a burst in thrombin generation and
fibrin turnover despite generous heparinization. Thrombin generation during
reperfusion after CABG associated with pulmonary vascular resistance and
postoperative myocardial damage.

Intensive Care Med. 2006 Jul 13; [Epub ahead of print] 

Point of care management of heparin administration after heart surgery : A
randomized, controlled trial.

Merlani PG, Chenaud C, Cottini S, Reber G, Garnerin P, de Moerloose P, Ricou B.

Service of Surgical Intensive Care, Department of Anesthesiology, Pharmacology
and Surgical Intensive Care, University of Geneva Hospitals and Faculty of
Medicine University of Geneva, Geneva, Switzerland, paolo.merlani@hcuge.ch.

OBJECTIVES: Determination of activated partial thromboplastin time (aPTT) is
used in coagulation management after heart surgery. Results from the central
laboratory take long to be obtained. We sought to shorten the time to obtain
coagulation results and the desired coagulation state and to reduce blood loss
and transfusions using point of care (POC) aPTT determination. DESIGN:
Randomized, controlled trial. SETTING: University-affiliated 20-bed surgical
ICU. PATIENTS AND PARTICIPANTS: Forty-two patients planned for valve surgery
(Valves) and 84 for coronary artery bypass grafting (CABG) with cardiopulmonary
bypass. INTERVENTIONS: Valves and CABG were randomized to postoperative
coagulation management monitored either by central laboratory aPTT (Lab group)
or by POC aPTT (POC group). Heparin was administered according to guidelines.
MEASUREMENTS AND RESULTS: POC aPTT results were available earlier than Lab aPTT
after venipuncture in Valves (3[Symbol: see text]+/-[Symbol: see text]2 vs.
125[Symbol: see text]+/-[Symbol: see text]68[Symbol: see text]min) and in CABG
(3[Symbol: see text]+/-[Symbol: see text]4 vs. 114[Symbol: see text]+/-[Symbol:
see text]62[Symbol: see text]min). Heparin was introduced earlier in the POC
group in Valves (7[Symbol: see text]+/-[Symbol: see text]23 vs. 13[Symbol: see
text]+/-[Symbol: see text]78[Symbol: see text]h, p[Symbol: see text]=[Symbol:
see text]0.01). Valves of the POC group bled significantly less than Valves in
the Lab group (647[Symbol: see text]+/-[Symbol: see text]362[Symbol: see text]ml
vs. 992[Symbol: see text]+/-[Symbol: see text]647ml, p[Symbol: see
text]<[Symbol: see text]0.04), especially during the first 8[Symbol: see text]h
after ICU admission. There was no difference in bleeding in CABG (1074[Symbol:
see text]+/-[Symbol: see text]869[Symbol: see text]ml vs. 1102[Symbol: see
text]+/-[Symbol: see text]620, p[Symbol: see text]=[Symbol: see text]NS). In
Valves, fewer patients in the POC group than in the Lab group needed blood
transfusions (1/21 vs. 8/21; p[Symbol: see text]=[Symbol: see text]0.03). No
difference was detected in CABG. CONCLUSIONS: In Valves in the POC group the
time to the desired coagulation state was reduced, as was the thoracic blood
loss, reducing the number of patients transfused. This improvement was not
observed in CABG. Side effects were similar in the two groups.

Resuscitation. 2006 Jul 7; [Epub ahead of print] 

Systematic review of percutaneous cardiopulmonary bypass for cardiac arrest or
cardiogenic shock states.

Nichol G, Karmy-Jones R, Salerno C, Cantore L, Becker L.

University of Washington, Harborview Center for Prehospital Emergency Care, Box
359727, 325 Ninth Ave., Seattle, WA 98104, United States; Emergency Services,
Harborview Medical Center, WA, United States.

BACKGROUND: Cardiogenic shock and cardiac arrest are common, lethal,
debilitating and costly. Percutaneous cardiopulmonary bypass is an innovative
strategy for treating these disorders that consists of rapid initiation of
cardiopulmonary bypass and extracorporeal maintenance of circulation until
restoration of an effective cardiac output. Multiple case reports suggest that
percutaneous bypass is efficacious in patients with these disorders but these
experiences have not been collated. Therefore, we have reviewed systematically
the published experience with percutaneous bypass in patients with cardiogenic
shock or cardiac arrest. OBJECTIVES: The objectives were to describe the
proportion of patients with cardiogenic shock or cardiac arrest who achieved
restoration of spontaneous circulation or survival to discharge with
percutaneous bypass. A secondary objective was to describe adverse effects
associated with percutaneous bypass, if feasible. DESIGN: Articles were
identified by using a comprehensive search of English-language MEDLINE from 1966
to September 2005. PATIENTS: Individuals in cardiogenic shock or cardiac arrest.
INTERVENTIONS: Percutaneous cardiopulmonary bypass. ANALYSIS: Effects were
summarized as inverse-variance weighted means, standard errors, median and
interquartile range. RESULTS: Included were 85 studies of 1494 patients with
cardiogenic shock, cardiac arrest or both. Studies were case reports,
case-series or case-control studies of heterogeneous interventions in
heterogeneous patients. The proportion of patients weaned was mean, 76.8+/-4.2%,
and median, 66.0% (IQR 50%, 100%). The proportion of patients who survived to
discharge was mean, 47.4+/-4.5%, and median 40.0% (IQR 20%, 75%). Fifty-two
studies included 533 patients in cardiogenic shock. The proportion of patients
who survived to discharge was mean, 51.6+/-6.5%, and median 38.5% (IQR 23.4%,
76.3%). Fifty-four studies included 675 patients in cardiac arrest. The
proportion of patients who survived to discharge was mean, 44.9+/-6.7%, and
median, 42.3% (IQR 15.4%, 75%). Five studies with 286 subjects had both patients
with cardiogenic shock or cardiac arrest. CONCLUSIONS: Percutaneous bypass is an
efficacious intervention in patients with cardiac arrest or cardiogenic shock.
Adequately-powered experimental studies of current percutaneous bypass
technologies are required to demonstrate whether it is safe, effective and
cost-effective.

Eur J Anaesthesiol. 2006 Jul 7;:1-5 [Epub ahead of print] 

Effect of alpha-stat vs. pH-stat strategies on cerebral oximetry during moderate
hypothermic cardiopulmonary bypass.

Nauphal M, El-Khatib M, Taha S, Haroun-Bizri S, Alameddine M, Baraka A.

American University of Beirut, Department of Anesthesiology, Beirut, Lebanon.

SummaryBackground and objectives: This study was undertaken to compare the
effect of alpha-stat vs. pH-stat strategies for acid-base management on regional
cerebral oxygen saturation (RsO2) in patients undergoing moderate hypothermic
haemodilution cardiopulmonary bypass (CPB). Methods: In 14 adult patients
undergoing elective coronary artery bypass grafting, an awake RsO2 baseline
value was monitored using a cerebral oximeter (INVOS 5100). Cerebral oximetry
was then monitored continuously following anaesthesia and during the whole
period of CPB. Mean +/- SD of RsO2, CO2, mean arterial pressure and haematocrit
were determined before bypass and during the moderate hypothermic phase of the
CPB using the alpha-stat followed by pH-stat strategies of acid-base management.
Alpha-stat was then maintained throughout the whole period of CPB. Results: The
mean baseline RsO2 in the awake patient breathing room air was 59.6 +/- 5.3%.
Following anaesthesia and ventilation with 100% oxygen, RsO2 increased up to
75.9 +/- 6.7%. Going on bypass, RsO2 significantly decreased from a pre-bypass
value of 75.9 +/- 6.7% to 62.9 +/- 6.3% during the initial phase of alpha-stat
strategy. Shifting to pH-stat strategy resulted in a significant increase of
RsO2 from 62.9 +/- 6.3% to 72.1 +/- 6.6%. Resuming the alpha-stat strategy
resulted in a significant decrease of RsO2 to 62.9 +/- 7.8% which was similar to
the RsO2 value during the initial phase of alpha-stat. Conclusion: During
moderate hypothermic haemodilutional CPB, the RsO2 was significantly higher
during the pH-stat than during the alpha-stat strategy. However, the RsO2 during
pH-stat management was significantly higher than the baseline RsO2 value in the
awake patient breathing room air, denoting luxury cerebral perfusion. In
contrast, the RsO2 during alpha-stat was only slightly higher than the baseline
RsO2, suggesting that the alpha-stat strategy avoids luxury perfusion, but can
maintain adequate cerebral oxygen supply-demand balance during moderate
hypothermic haemodilutional CPB.

Circulation. 2006 Jul 4;114(1 Suppl):I43-8. 

Intraoperative red blood cell transfusion during coronary artery bypass graft
surgery increases the risk of postoperative low-output heart failure.

Surgenor SD, DeFoe GR, Fillinger MP, Likosky DS, Groom RC, Clark C, Helm RE,
Kramer RS, Leavitt BJ, Klemperer JD, Krumholz CF, Westbrook BM, Galatis DJ,
Frumiento C, Ross CS, Olmstead EM, O'Connor GT.

Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03756.
Stephen.D.Surgenor@Hitchcock.ORG.

BACKGROUND: Hemodilutional anemia during cardiopulmonary bypass (CPB) is
associated with increased mortality during coronary artery bypass graft (CABG)
surgery. The impact of intraoperative red blood cell (RBC) transfusion to treat
anemia during surgery is less understood. We examined the relationship between
anemia during CPB, RBC transfusion, and risk of low-output heart failure (LOF).
METHODS AND RESULTS: Data were collected on 8004 isolated CABG patients in
northern New England between 1996 and 2004. Patients were excluded if they
experienced postoperative bleeding or received > or = 3 units of transfused
RBCs. LOF was defined as need for intraoperative or postoperative intra-aortic
balloon pump, return to CPB, or > or = 2 inotropes at 48 hours. Having a lower
nadir HCT was also associated with an increased risk of developing LOF (adjusted
odds ratio, 0.90; 95% CI, 0.82 to 0.92; P=0.016), and that risk was further
increased when patients received RBC transfusion. When adjusted for nadir
hematocrit, exposure to RBC transfusion was a significant, independent predictor
of LOF (adjusted odds ratio, 1.27; 95% CI, 1.00 to 1.61; P=0.047). CONCLUSIONS:
In this study, we observed that exposure to both hemodilutional anemia and RBC
transfusion during surgery are associated with increased risk of LOF, defined as
placement of an intraoperative or postoperative intra-aortic balloon pump,
return to CPB after initial separation, or treatment with > or = 2 inotropes at
48 hours postoperatively, after CABG. The risk of LOF is greater among patients
exposed to intraoperative RBCs versus anemia alone.

J Thorac Cardiovasc Surg. 2006 Jul;132(1):80-8. 

Intermittent pressure augmentation during retrograde cerebral perfusion under
moderate hypothermia provides adequate neuroprotection: an experimental study.

Kawata M, Takamoto S, Kitahori K, Tsukihara H, Morota T, Ono M, Motomura N,
Murakami A, Suematsu Y.

Department of Cardiothoracic Surgery, Graduate School of Medicine, University of
Tokyo, Tokyo, Japan. mkawata-ths@umin.ac.jp

OBJECTIVE: For cerebral protection during aortic surgery, we introduced a novel
retrograde cerebral perfusion method with intermittent pressure augmentation. We
then assessed whether this novel method provides benefits similar to those
provided by antegrade selective cerebral perfusion. METHODS: Eighteen dogs were
randomly divided into 3 groups: the RCP-INT group, intermittent-retrograde
cerebral perfusion at 15 mm Hg with intermittent pressure augmentation to 45 mm
Hg (n = 6); the ASCP group, antegrade selective cerebral perfusion at a flow
rate of 10 mL x kg(-1) x min(-1) (n = 6); and the sham group, no circulatory
arrest (n = 6). Cooling (26 degrees C) with cardiopulmonary bypass and 60
minutes of circulatory arrest were performed in the RCP-INT and ASCP groups. The
levels of tau protein in the cerebrospinal fluid and the diameters of the
retinal vessels were measured. The neurologic deficit scores and the
histopathologic damage scores of the brains were determined. RESULTS: The total
postoperative tau protein levels (calculated as the area under the curve) did
not differ significantly between the RCP-INT and ASCP groups (203 +/- 87 pg x
mL(-1) x h vs 154 +/- 69 pg x mL(-1) x h, P = .95). The retinal vessels were
effectively dilated at an augmented pressure of 45 mm Hg in the RCP-INT group.
The total neurologic deficit score (0 = normal, 500 = brain death) and
histopathologic damage score (0 = normal, 40 = worst) were not significantly
different between the RCP-INT and ASCP groups (neurologic deficit score: 75 +/-
21 vs 70 +/- 21, P = .98; histopathologic damage score: 13.5 +/- 1.5 vs 14.2 +/-
1.3, P = .84). CONCLUSIONS: Intermittent augmented pressure dilated the cerebral
vessels, allowing adequate blood supply without injuring the brain. This
retrograde cerebral perfusion method provides adequate neuroprotection during
moderate hypothermia.