Paul Le Besnerais

Inflammatory response to cardiopulmonary bypass using roller or centrifugal pumps

BACKGROUND The inflammatory response in 29 patients undergoing coronary artery bypass grafting using either roller or centrifugal (CFP) pumps was evaluated in a prospective study. METHODS Patients were randomized in roller pump (n = 15) and CFP (n = 14) groups. Terminal complement complex activation (SC5b-9) and neutrophil activation (elastase) were assessed during the operation. Cytokine production (tumor necrosis factor-alpha, interleukin-6, interleukin-8) and circulating adhesion molecules (soluble endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1) were assessed after the operation. RESULTS Release of SC5b-9 after stopping cardiopulmonary bypass and after protamine administration was higher in the CFP group (p = 0.01 and p = 0.004). Elastase level was higher after stopping cardiopulmonary bypass using CFP (p = 0.006). Multivariate analysis confirmed differences between roller pump and CFP groups in complement and neutrophil activation. After the operation, a significant production of cytokines was detected similarly in both groups, with peak values observed within the range of 4 to 6 hours after starting cardiopulmonary bypass. However, interleukin-8 levels were higher using CFP 2 hours after starting cardiopulmonary bypass (p = 0.02). Plasma levels of adhesion molecules were similar in both groups within the investigation period. CONCLUSIONS During the operation, CFP caused greater complement and neutrophil activation. After the operation, the inflammatory response was similar using either roller pump or CFP.

Heparin-coated circuits and aprotinin prime for coronary artery bypass grafting

BACKGROUND The biocompatibility of an extracorporeal circuit is improved by heparin bonding onto its inner surface. To determine the effect of heparin-coated circuits for cardiopulmonary bypass with aprotinin prime on postoperative recovery and resource utilization, a prospective study was done in 102 patients undergoing coronary artery bypass grafting with full systemic heparinization. METHODS Patients were randomly allocated to be treated with either a heparin-coated circuit (n = 51) or an uncoated circuit (n = 51). Differences in blood loss, need for blood transfusion, morbidity, and intensive care stay were analyzed. RESULTS No differences in blood loss and need for blood transfusion were found between the groups. The relative risk for adverse events in the heparin-coated group was 0.29 (95% confidence interval ranging from 0.10 to 0.80). Adverse events included myocardial infarction (2 patients in the uncoated group versus 0 in the heparin-coated group), rethoracotomy for excessive bleeding (1 versus 2), rhythm disturbance (7 versus 2), respiratory insufficiency (4 versus 0), and neurologic dysfunction (2 versus 0). The lower incidence of adverse events in the heparin-coated group was associated with a shorter intensive care stay (median, 2 days; range, 2 to 5 days) compared with the uncoated group (median, 3 days; range, 2 to 19 days, p = 0.03). The cost savings of 1 day of intensive care stay counterbalanced the additional costs of heparin-coated circuits. CONCLUSIONS The use of heparin-coated circuits for cardiopulmonary bypass with aprotinin prime resulted in a significant reduction in mobidity in the early postoperative phase and a concomitant decrease in intensive care stay, resulting in important cost savings.

Heparin coating with aprotinin reduces blood activation during coronary artery operations.

BACKGROUND This study was performed to evaluate whether the combination of heparin-coated extracorporeal circuits (ECC) and aprotinin treatment reduce blood activation during coronary artery operations. METHODS Sixty patients were prospectively divided into two groups (heparin-coated ECC and uncoated ECC groups), which were comparable in terms of age, sex, left ventricular function, preoperative aspirin use and consequent intraoperative aprotinin use, number of grafts, duration of aortic cross-clamping, and duration of cardiopulmonary bypass. Blood activation was assessed at different times during cardiopulmonary bypass by determination of complement activation (C3 and C4 activation products C3b/c and C4b/c and terminal complement complex), leukocyte activation (elastase), coagulation (scission peptide fibrinopeptide 1 + 2), and fibrinolysis (D-dimers). RESULTS Univariate analysis showed that heparin-coated ECC, under conditions of standard heparinization, did not reduce perioperative blood loss and need for transfusion. Heparin coating, however, reduced maximum values of C3b/c (446 +/- 212 nmol/L versus 632 +/- 264 nmol/L with uncoated ECC; p = 0.0037) and maximum C4b/c values (92 +/- 48 nmol/L versus 172 +/- 148 nmol/L with uncoated ECC; p = 0.0069). Levels of terminal complement complex, elastase, fibrinopeptide 1 + 2, and D-dimers were not significantly modified by the use of heparin-coated ECC. Multivariate analysis showed that the intergroup differences in maximum C3b/c and C4b/c values were more pronounced in women in part with high baseline values of C3b/c. We also found that aprotinin contributed to the reduction of maximum values of fibrinopeptide 1 + 2 and D-dimers, whereas heparin coating had no significant influence on these parameters. CONCLUSIONS We found no evidence of combined properties of heparin-coated ECC and aprotinin in reducing complement activation, coagulation, and fibrinolysis. We therefore recommend use of both together to achieve maximal reduction of blood activation during cardiopulmonary bypass for coronary artery operations.

Cardiac troponin I release after open heart surgery: a marker of myocardial protection?

BACKGROUND Unlike creatine kinase MB isoenzyme, cardiac troponin I (cTnI) is a highly specific marker of myocardial injury. Its release has recently been studied after coronary artery bypass grafting operation. However, its significance after open heart surgery (OHS) remains to be determined. This protein release could be a marker of myocardial protection. We sought to study cTnI release after OHS in patients with normal coronary arteries and to compare it with cTnI release in patients after coronary artery bypass graft (CABG) surgery. METHODS Eighty-five patients undergoing OHS and 86 patients undergoing CABG were enrolled in the study. CTnI concentrations were measured in serial venous blood samples drawn before surgery and immediately, 12 hours, 24 hours, 48 hours, and 5 days after aortic unclamping. RESULTS In the OHS group and in the CABG group without acute myocardial infarction (AMI), cTnI peaked at 12 hours postoperatively (6.35 +/- 6.5 and 5.38 +/- 8.55 ng/mL, respectively) and normalized on day 5 postoperatively (0.57 +/- 2 and 0.72 +/- 1.62 ng/mL, respectively). CTnI concentration did not differ significantly between the OHS group and the CABG group in the absence of AMI for any samples considered. In the CABG group, 2 patients had AMI. In the OHS group, cTnI levels at 12 hours postoperatively were found to correlate closely with CPB and aortic cross-clamping (ACC) times, contrary to the CABG group, which correlated only with occurrence of AMI. CTnI release was independent of age and ejection fraction in either group. CONCLUSIONS cTnI release in patients after OHS with normal coronary arteries has the same profile as cTnI release in patients after CABG in the absence of AMI. However, its peak at 12 hours postoperatively is only correlated to ACC and CPB times, which is contrary to cTnI release after CABG surgery. This observation suggests that cTnI could be a marker of myocardial ischemia after OHS.

Myocardial recovery after mechanical support for acute myocarditis: is sustained recovery predictable?

BACKGROUND At present, myocardial recovery with mechanical support for acute myocarditis is a more frequently observed issue. However, predictive parameters of a sustained myocardial recovery are still under investigation. METHODS Two recent cases of mechanical support for acute lymphocytic myocarditis with two different outcomes are reported. Literature about this disease and predictability of a sustainable myocardial recovery are reviewed. RESULTS Acute lymphocytic myocarditis is an individual entity whose outcome is associated with the importance of healed cell damage. Unfortunately, there are no available means of quantifying the fibrotic scar and endomyocardial biopsy has a high percentage of false-negative results. Echocardiographic assessment of systolic and diastolic cardiac function is difficult while under mechanical support and its significance is not obvious. Forthcoming development of Doppler could better correlate myocardial contractility and histology to be predictive of a sustained recovery after acute myocarditis under mechanical support. CONCLUSIONS Long-lasting recovery after mechanical support for acute myocarditis remains unpredictable in our experience. More predictive factors are needed.

Clinical outcome after coronary surgery with heparin-coated extracorporeal circuits for cardiopulmonary bypass

In this prospective randomized trial, we studied whether heparin-coated extracorporeal circuits (ECC), known to reduce complement activation, could improve the clinical outcome of 200 patients undergoing coronary artery surgery. Patients have been divided into two groups (heparin-coated ECC and uncoated ECC groups) which were similar in terms of age, gender, left ventricle function, preoperative aspirin use and consequent intraoperative aprotinin use, number of grafts, duration of aortic cross-clamping and cardiopulmonary bypass. Univariate analysis showed that heparin coating did not reduce significantly postoperative bleeding (640 ± 311 versus 682 ± 342 ml with uncoated ECC) nor the need for transfusion (19% of patients versus 25% with uncoated ECC). Adverse events, including all mortality and morbidity noticed during the five first postoperative days, occurred in 20 patients of the uncoated ECC group and in eight patients of the heparin-coated ECC group (p = 0.013). The most frequent complications were supraventricular arrhythmias that occurred in 13 patients of the uncoated ECC group and in four patients of the heparin-coated ECC group (p = 0.02). Multivariate analysis by stepwise logistic regression showed that only heparin coating of the ECC was shown as a significant predictive factor of adverse events reduction (p = 0.01; odds ratio = 0.34). These data suggest that heparin coating reduced postoperative complications in patients undergoing coronary artery surgery.

Clinical implantation of the wearable Baxter Novacor ventricular assist system.

Implantation of the wearable Novacor electrically powered left ventricular assist system was performed on March 16, 1993, in a 44-year-old man hospitalized for an acute episode of myocardial decompensation after a 6-year history of dilated cardiomyopathy. He was rehabilitated fully and became ambulatory, awaiting a suitable cardiac graft for 59 days. He is now back to work, enjoying a normal life. This case illustrates the progress made by miniaturization of the external components of the system. General acceptance of the system and psychological adaptation to the new way of life were remarkable.

Immunologic events and long-term survival after combined heart and kidney transplantation: a 12-year single-center experience.

BACKGROUND In this study we compare the incidence of cardiac rejection and long-term survival after combined heart and kidney transplantation (HK) and single heart transplantation (H). Combined HK transplantation is a surgical option for patients with irreversible cardiac and renal failure. However, long-term results of combined HK transplantation on immunologic events and patient survival remain unknown. METHODS Between 1988 and 1997, 12 consecutive patients underwent combined HK transplantation (HK group) at a single institution. A control group (H group) of 24 single heart transplant recipients operated on within the same period was matched for age, pre-operative pulmonary vascular resistance, hepatic insufficiency and gender mismatch. Recipients and donors were ABO compatible without HLA antigen matching. All patients received immediate triple immunosuppression that included cyclosporine. Because of early renal dysfunction, cyclosporine was switched to anti-thymocyte globulin in 5 patients from the HK group and in 1 patient from the H group (p = 0.01). RESULTS Actuarial freedom from heart rejection at 6 months and at 1 year following transplantation averaged 90 +/- 9% and 70 +/- 14% in the HK group, and 65 +/- 10% and 49 +/- 11% in the H group, respectively (p = 0.023). Actuarial survival at 1, 5 and 12 years was not significantly different between groups, at 66%, 55% and 28% in the HK group, and 66%, 44% and 32% in the H group, respectively (p = 0.66). CONCLUSION The incidence of cardiac rejection was significantly lower. Long-term survival in the HK group was similar to that in the H group. Putative mechanisms of decreased cardiac rejection in the HK group include allogeneic stimulation, donor-derived dendritic cells and induction by anti-thymocyte globulins. The need for long-term immunosuppression may be reduced after combined heart and kidney transplantation.

Inflammatory response to cardiopulmonary bypass using two different types of heparin-coated extracorporeal circuits

Previous reports have highlighted the disparity in biocompatibility of two differently engineered heparin coatings during the cardiopulmonary bypass (CPB) procedure. The aim of this prospective study was to evaluate the impact of the difference in haemocompatibility provided by either the Duraflo II equipment or the Carmeda equipment in the terminal inflammatory response observed after coronary artery surgery. Thirty patients were randomly allocated to two groups to be operated on using either Duraflo II equipment (group I) or Carmeda equipment (group 2) for extracorporeal circulation (ECC). Initial inflammatory response was assessed by terminal complement complex activation (SC5b-9). The late inflammatory response observed in the postoperative period was assessed by measuring cytokine production (tumour factor necrosis (TNFα), interleukin IL-6, interleukin IL-8) and circulating concentrations of adhesion molecules (ELAM-1, ICAM-1). The release of SC5b-9 after CPB and after protamine administration was lower in group 2 than in group 1 (p = 0.0002 and p = 0.006, respectively). A significant production of cytokines was detected in both groups with peak values observed within the time range of 4-6 h after the start of CPB. However, no difference was observed between the groups except for the IL-8 level in group 2, which was lower 2 h after the start of CPB (p = 0.01). Plasma levels of adhesion molecules were similar in both groups within the investigation period. Although the Carmeda equipment was more effective in reducing complement activation, the late inflammatory response was similar using either the Duraflo II or Carmeda equipment for extracorporeal circulation as reflected by the changes of cytokine and circulating adhesion molecule levels.

Mechanical bridge to transplantation: When is too early? When is too late?

BACKGROUND Optimal timing of implantation of a mechanical circulatory support system in the treatment of acute cardiogenic shock is still unsettled. The issue has been addressed in a retrospective analysis of a group of 98 patients in cardiogenic shock refractory to medical therapy who were candidates for cardiac transplantation, admitted from 1987 to 1994. METHODS The treatment included reinforced inotropic support by addition of phosphodiesterase inhibitors to sympathomimetic agents. The patients who did not improve were immediately brought to the operating room for mechanical circulatory support system implantation. RESULTS The overall survival in the group of 28 patients selected for mechanical bridge is 50%. No predictive factors of death or multiorgan failure while on the device could be identified, suggesting a lack of contraindications to mechanical circulatory support system implantation. CONCLUSIONS The high death rate in patients maintained on medical therapy because of initial improvement as they are awaiting transplantation suggests the benefit of a rapid semielective implantation of an intracorporeal device.