Validity of the sonographic measurement of the diameters of the ascending aorta in rats.

PURPOSE: The objective of this investigation was to compare transthoracic ultrasound (US) determinations of ascending aortic diameters in rats with video microscopy (VM), the current standard for measuring aortic diameters in rats. MATERIALS AND METHODS: The diameter of the ascending aorta was measured in 111 adult Lewis male rats, by VM and US, with a 9 MHz probe, before and after intervention for induction of experimental aneurysm of the ascending aorta. RESULTS: The Bland-Altman test showed a high degree of agreement between the two methods, with a bias of only 0.23 mm (95 % confidence limits - 0.86 - 0.39 mm). Also, the measurements obtained by US correlated highly (r = 0.83, p < 0.0001) with those obtained by VM. Rat ascending aortic diameters obtained both by VM and US correlated significantly with the weight (r = 0.62 and r = 0.39, respectively), and with the age of the animals (r = 0.74 and r = 0.49, respectively). CONCLUSION: This study demonstrates that noninvasive US ascending aortic measurements are a reliable supplement to VM for the development of an ascending aortic aneurysm model, and for monitoring the efficiency of novel therapeutic agents.

Risk factors for post-cardiopulmonary bypass vasoplegia in patients with preserved left ventricular function.

BACKGROUND: Although vasodilatory shock (VS) is one of the main complications of cardiopulmonary bypass (CPB), its pathophysiologic basis remains unclear. The aim of this study was to identify predisposing factors for the development of VS after CPB independent of ventricular function. METHODS: Thirty-six patients undergoing coronary artery bypass grafting who developed VS were compared with 72 control patients without post-CPB cardiogenic or vasoplegic shock, in a 2:1 case control study. Patients and controls underwent the same anesthetic protocol and were matched by age, sex, operation date, and left ventricle ejection fraction. RESULTS: Preoperative and intraoperative patient characteristics were not significantly different between the two groups. Preoperative use of angiotensin-converting enzyme inhibitors and intravenous heparin were independent predictors for post-CPB VS by multivariate analysis (relative risk of 2.26 and 2.78, respectively). Intensive care unit stay and hospital stay were significantly longer in VS cases than controls, without any difference in early postoperative mortality. CONCLUSIONS: The only independent risk factors for postoperative VS identified were preoperative use of angiotensin-converting enzyme inhibitors and intravenous heparin. These risk factors were independent of age, gender, anesthetic protocol, and left ventricle ejection fraction.

Closed drainage using redon catheters for poststernotomy mediastinitis: results and risk factors for adverse outcome.

BACKGROUND: Several different surgical techniques have been described for the treatment of poststernotomy mediastinitis. The present study was undertaken to evaluate the midterm results of primary closed drainage using Redon catheters and to identify risk factors for adverse outcome. METHODS: Hospital records of 72 patients in whom poststernotomy mediastinitis developed and who underwent closed drainage with Redon catheters between April 1, 1996, and December 31, 1999, were reviewed. Follow-up was complete and averaged 11.8 +/- 11.5 months. RESULTS: Of the 25 deaths (34.7%) recorded, 15 were directly attributable to mediastinitis. Actuarial estimates for freedom from mediastinitis-related death were 80.1% at 1 month and 77.4% at 1 year, 2 years, and 3 years. Logistic regression identified older age (odds ratio, 1.1; 95% confidence interval, 1.02 to 1.18), incubation time of 14 days or less (6.5; 1.33 to 31.4), and methicillin-resistant Staphylococcus aureus (5.8; 1.2 to 27.2) as independent risk factors for mediastinitis-related death. Reintervention for recurrent mediastinitis was necessary in 9 patients (12.5%) and occurred at a mean interval of 18.7 +/- 13.5 days from the first debridement. Actuarial estimates for freedom from reintervention were 87.1% at 1 month and 85.2% at 1 year, 2 years, and 3 years. The combined end point of treatment failure (mediastinitis-related death or reintervention) was recorded in 9 patients (26.4%). Actuarial estimates for freedom from treatment failure were 74.3% at 1 month and 72.7% at 1 year, 2 years, and 3 years. Logistic regression identified older age (1.01; 1.02 to 1.18), preoperative renal insufficiency (6.8; 1.04 to 44.5), and methicillin-resistant S aureus infection (4.8; 1.04 to 22.33) as independent risk factors for treatment failure (includes mediastinitis-related death and reintervention [with or without death]). CONCLUSIONS: Primary closed drainage using Redon catheters is an effective and simple treatment for most patients in whom poststernotomy mediastinitis develops. However, patients with methicillin-resistant S aureus infection or recurrent mediastinitis may benefit from a more aggressive approach.

Effect of variation in systemic blood flow on plasma TNF-alpha in a pig model with left ventricular assist device.

Tumor necrosis factor-alpha (TNF-alpha) release has been implicated in a sepsis-like syndrome following cardiopulmonary bypass (CPB). This also may be important in patients who have had a left ventricular assist device (LVAD) implanted. This report investigates the effect of reducing systemic blood flow on hemodynamic response, mixed venous oxygen saturation (SvO(2)), and the release of TNF-alpha. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF-alpha in the femoral artery (FA) and superior mesenteric vein (SMV) was measured at baseline and following systemic blood flow changes. Simultaneously, hemodynamic parameters and oxygen saturation in the pulmonary artery (SvO(2)) were measured. Following reductions in systemic blood flow, plasma TNF-alpha increased gradually to a maximum level at a systemic blood flow of 20%. There was no significant difference between TNF-alpha levels in the SMV and the FA. There was a significant (p < 0.05) correlation between cardiac index, stroke volume index, and TNF-alpha. The SvO(2) decreased significantly (p < 0.05) at a systemic blood flow of 30 and 20%. A rise in TNF-alpha occurred when the SvO(2) was less than 75%. The data demonstrate that a reduction in systemic blood flow causes an increase in plasma TNF-alpha. This can lead to the development of a sepsis-like syndrome in a group of patients who already are hemodynamically compromised. While weaning short-term LVAD support, rapid diminution of the cardiac output and the pump flow must be avoided.

Intestinal tissue oxygenation and tumor necrosis factor-alpha release during systemic blood flow changes in pigs with left ventricular assist devices.

We previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) increased following a reduction in systemic blood flow to 60% or less of the original cardiac output using a left ventricular assist device (LVAD). The aim of this study was to investigate the effect of reducing systemic blood flow on tissue oxygenation in the gastrointestinal tract (GIT) and the consequences of this on TNF-alpha release. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF-alpha of the superior mesenteric vein was measured at baseline and during systemic blood flow changes. Simultaneously, pH, lactate, oxygen delivery index (DO(2)I), oxygen consumption index (VO(2)I), and oxygen extraction (O(2)ER) in the GIT were measured. The pH decreased and the lactate level increased significantly (p < 0.05) at a systemic blood flow of 50% or less. The VO(2)I was positively correlated with DO(2)I. The O(2)ER increased significantly (p < 0.05) with reductions in systemic blood flow to 30% or less. There was a significant (p < 0.01) correlation between TNF-alpha and O(2)ER at levels higher than 55%. These data demonstrate that the GIT oxygenation is inadequate with a reduction in systemic blood flow to 50% and that GIT oxygenation becomes critical at a reduction of 30%. During LVAD weaning, careful attention must be given to the GIT. The pH and lactate may be good markers of the adequacy of tissue oxygenation in the GIT.

Mechanical circulatory support for advanced heart failure: effect of patient selection on outcome.

BACKGROUND: Use of wearable left ventricular assist systems (LVAS) in the treatment of advanced heart failure has steadily increased since 1993, when these devices became generally available in Europe. The aim of this study was to identify in an unselected cohort of LVAS recipients those aspects of patient selection that have an impact on postimplant survival. METHODS AND RESULTS: Data were obtained from the Novacor European Registry. Between 1993 and 1999, 464 patients were implanted with the Novacor LVAS. The majority had idiopathic (60%) or ischemic (27%) cardiomyopathy; the median age at implant was 49 (16 to 75) years. The median support time was 100 days (4.1 years maximum). Forty-nine percent of the recipients were discharged from the hospital on LVAS; they spent 75% of their time out of the hospital. For a subset of 366 recipients, for whom a complete set of data was available, multivariate analysis revealed that the following preimplant conditions were independent risk factors for survival after LVAS implantation: respiratory failure associated with septicemia (odds ratio 11.2), right heart failure (odds ratio 3.2), age >65 years (odds ratio 3.01), acute postcardiotomy (odds ratio 1.8), and acute infarction (odds ratio 1.7). For patients without any of these factors, the 1-year survival after LVAS implantation including the posttransplantation period was 60%; for the combined group with at least 1 risk factor, it was 24%. CONCLUSIONS: Careful selection, specifically implantation before patients become moribund, and improvement of management may result in improved outcomes of LVAS treatment for advanced heart failure.

Long-term mechanical circulatory support with the wearable Novacor left ventricular assist system.

OBJECTIVE: As of July 1st 1999, 36 European patients have lived for more than 1 year supported by the Novacor wearable electric left ventricular assist system (LVAS). All were unresponsive to maximum medical therapy, prior to implantation. These patients offer an unique opportunity to evaluate the feasibility of long-term ambulatory mechanical circulatory support as a therapeutic option for patients in profound cardiac failure. METHODS: Data was obtained from the Novacor European Registry. RESULTS: At the time of implantation, median age was 55 (18-67) years. Aetiology was ischemic (9, 25%) or idiopathic (26, 72%) cardiomyopathy, and myocarditis (1, 3%). Median duration of LVAS support was 1.49 (1. 03-4.10) years. Eight recipients had LVAS support times >2 years, of which two were >3 years and one >4 years. The median time spent outside the hospital was 1.27 (0.58-3.83) years, representing 82% of the duration of LVAS support. No mechanical failure was observed during the entire observation period. One pump was replaced electively after 3.67 years due to pump driver wear-out. Twelve patients (33%) are currently on support while 17 were transplanted (14, 39%) or weaned (3, 8%). Seven (19%) patients died after a median of 1.24 years circulatory support. CONCLUSIONS: Experience with long-term Novacor LVAS recipients has demonstrated effective rehabilitation in this group of patients with refractory advanced heart failure. This suggests that LVAS therapy may offer a safe and realistic option for patients for whom no other effective therapy is available. The patient sub-population that would benefit most from this therapy remains to be defined.

[External ventricular support in primary cardiogenic shock]. / Dérivations ventriculaires externes dans le choc cardiogénique primaire.

Primary cardiogenic shock is a common condition with a high mortality rate. In this indication, mechanical assist plays an important part and has improved a lot over the last decade. The authors report their experience with the same assist device in patients with primary cardiogenic shock. Nineteen patients (9 dilated cardiomyopathies, 7 myocardial infarctions, 2 myocardities, 1 undetermined) were treated with an external mechanical ventricular assist device (Thoratec, Berkeley, U.S.). Fourteen patients received a biventricular assist and 5 had a uni-left ventricular assist device. Four of the 19 patients were completely weaned off their ventricular assist after 13, 27, 36 and 94 days, respectively. Ten patients underwent transplantation after an average of 43 days (range 8-95 days). Of the 19 patients, 7 had a portable console allowing autonomous ambulation. Five patients died under mechanical assistance (26.9%) and 3 patients died after transplantation. Three patients required temporary haemodialysis; 4 suffered embolic complications; 4 had mediastinal haemorrhages; 4 had bleeding from other sites, and 6 suffered from late tamponnade. Fourteen patients had at least one infectious episode. The authors conclude that, in patients referred for severe primary cardiogenic shock, the implantation of an external biventricular assist is a reliable option, allowing sequential weaning or being a bridge to transplantation in non-dependent patients, providing they are severely selected.

Pseudointima in inflow conduits of left ventricular assist devices.

BACKGROUND: Explant analysis of left ventricular assist systems (LVAS) should permit a better evaluation of long-term evolution of materials and tissue healing in patients supported by mechanical devices and a precise understanding of embolic phenomena, observed clinically. METHODS: Five Novacor LVAS and their conduits have been explanted after 156 days (range 61-226 days) of mechanical support. The pseudo-intima (PI) developed in the inflow and outflow conduits was characterized microscopically, using monoclonal antibodies. RESULTS: The morphological aspects of PI were quite different in the inflow and outflow conduits. Blood coagulation between the basal surface of the PI and the Dacron tube, irregular collagen type I matrix with plasma infiltration, macrophages, and neutrophil granulocyte elastase characterized the nonadherent, loose, and potentially thrombogenic PI growth in the inflow conduit. The PI from collagen types I and IV with circumferentially oriented alpha-smooth muscle cell actin-positive cells was anchored to the outflow conduits. CONCLUSIONS: The observations, which have to be confirmed by a more extensive study on a larger number of specimens, suggest the role of the biomaterial itself, as well as the configuration, physical characteristics, and rheology in the conduit. They also suggest that thromboembolic complications of LVAS may eventually be related to this host tissue response.

The European experience of Novacor left ventricular assist (LVAS) therapy as a bridge to transplant: a retrospective multi-centre study.

OBJECTIVE: Artificial heart devices have suffered from a negative press based on the early Jarvik experience of the 1980s. This is in stark contrast to realities of current left ventricular assist (LVAS) therapy. The Novacor N100 PC wearable left ventricular assist system (LVAS) was introduced in Europe in late 1993. This system allows implanted recipients to be completely autonomous with the system controlled by a small computer and powered by rechargeable batteries. This report represents the initial European experience with the Novacor LVAS. METHODS: Since the system was introduced with regulatory approval as a commercial product, clinicians were not bound by the constraints of a study protocol and only minimal data were collected. This report presents the results of a retrospective study of 118 consecutive patients who had the LVAS implanted as a bridge to transplant, in 19 centres over the three year period ending in November 1996. RESULTS: Mortality and morbidity varied widely between centres. The median implant time was 115 days (0-585 days) and 33% of patients returned home, supported by the LVAS. The overall survival on LVAS was 64%. The major causes of death were infection (14%) and MOF (6%). There were no significant device or system failures despite a cumulative patient experience of 24.8 years outside of a hospital environment. Patient selection and management varied greatly between centres and this was reflected in disparate outcomes. CONCLUSIONS: Optimal selection and management of LVAS patients has still to be established. While the data available for this report lacked the detail necessary to demonstrate direct causal relationships between selection and management, it was clear from the inter-centre differences that these two factors have a major impact on outcomes. This early experience has directed attention towards improved management regimes. Given the results obtained from the best centres and the ability to discharge patients to lead near-normal lives in the community, the authors believe that the Novacor LVAS now offers a real therapeutic alternative for selected end-stage heart failure patients for whom a donor heart is unavailable or who are unsuitable for transplantation.

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.

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.

Preconditioning with cromakalim improves long-term myocardial preservation for heart transplantation.

BACKGROUND: Myocardial preservation for heart transplantation relies on hyperkalemic cardiac arrest and hypothermic storage. Our study investigated whether pretreatment with a potassium-channel opener (cromakalim) before prolonged storage in an extracellular fluid improves left ventricular recovery. METHODS: Rabbit hearts were submitted to 6-hours' cold storage and assessed on a blood-perfused isolated heart preparation. Hemodynamic recovery, enzyme release (creatine kinase and lactate dehydrogenase), and adenine nucleotide content were determined. Five groups were tested: control (n=6), no ischemia; UW group (n=7), hearts arrested with and stored in University of Wisconsin solution; STH group (n=5), hearts arrested with and stored in St. Thomas' Hospital solution; cromakalim group (n=6), hearts pretreated with cromakalim (30 microg/kg) before arrest with and storage in St. Thomas' Hospital solution; and glibenclamide group (n=5), hearts pretreated with cromakalim followed by glibenclamide (a potassium-channel blocker) before arrest with and storage in St. Thomas' Hospital solution. RESULTS: Hemodynamic recovery was improved and enzyme release was lower in the UW group than in the STH group. Compared with the STH group, the group pretreated with cromakalim had significantly decreased left ventricular end-diastolic pressures, increased left ventricular developed pressures, increased maximal values of positive and negative rates of rise of left ventricular pressure, and increased time constant of isovolumetric relaxation. Hemodynamic recovery was similar in the UW group and cromakalim groups. Glibenclamide did not abolish the effects of cromakalim. None of the protocols affected myocardial energy stores. CONCLUSION: Pretreatment with cromakalim affords additional protection to that provided by cardioplegic arrest and prolonged cold storage using an extracellular solution. The intracellular mechanisms involved remain to be determined.

Cardiac operations in octogenarians: perioperative risk factors for death and impaired autonomy.

BACKGROUND: With the progressive aging of western populations, cardiac surgeons are increasingly faced with elderly patients. METHODS: We reviewed the records of 191 consecutive patients aged 80 years or older (mean age, 83 +/- 2.4 years) who underwent a cardiac surgical procedure at our institution from 1991 through 1996. RESULTS: Ninety-eight patients were men. Preoperatively, 32% of patients were in New York Heart Association class III or IV, and mean left ventricular ejection fraction was 0.55 +/- 0.02. One hundred ten patients (58%) underwent aortic valve replacement, 47 (25%) had coronary artery bypass grafting, 26 (14%) had combined aortic valve replacement and coronary artery bypass grafting, 5 (3%) underwent mitral valve replacement, and 3 (1.6%) had other procedures. Postoperative complications occurred in 69.1% of patients. The hospital mortality rate was 16.2%. Actuarial survival estimates at 1 year, 3 years, and 5 years were 79.2%, 74.9%, and 56.2%, respectively. Multivariate predictors (p < 0.05) of hospital death were preoperative pulmonary hypertension and lower left ventricular ejection fraction. Multivariate predictors of late death were combined aortic valve replacement and coronary artery bypass grafting and female sex. Sixty-four percent of long-term survivors were fully autonomous, and female sex was the only independent predictor of impaired autonomy. Eighty-three percent of survivors were satisfied with their present quality of life. CONCLUSIONS: Cardiac operations can be performed in octogenarians with a favorable long-term outcome. Earlier referral and intervention is mandatory to improve results in this patient population.

Pretransplantation risk factors for death after heart transplantation: the Henri Mondor experience.

BACKGROUND AND METHODS: Risk factors for death after primary heart transplantation were identified by analyzing our total experience with 234 patients who underwent transplantation at our institution from May 28, 1979, to May 27, 1996. RESULTS: There were 205 male and 29 female patients. Mean recipient age was 48.5+/-10.9 years (standard deviation). Recipient diagnosis included ischemic cardiomyopathy in 103 (44%), idiopathic cardiomyopathy in 98 (42%), valvular heart disease in 17 (7%), congenital heart disease in 4 (2%), and other diagnoses in 12 (5%) patients. Donor age was 32+/-10.2 years. Graft ischemic time was 138.1+/-51.8 minutes. The operative mortality rate was 23.5%. Actuarial survival estimates for all patients at 1, 5, and 10 years were 62%, 50%, and 44%, respectively. The three most common causes of death (both early and late) after primary heart transplantation were infection (27.4%), acute rejection (18.9%), and early graft failure (17.9%). Multivariate logistic regression analysis identified older recipient age (p = 0.007), higher preoperative pulmonary vascular resistance (p = 0.01), recipient preoperative hepatic insufficiency (p = 0.001), and gender mismatch (p = 0.02) as independent predictors of early death (within 3 months of the procedure). Multivariate proportional hazard regression analysis revealed that recipient idiopathic cardiomyopathy (p = 0.02) and recipient preoperative liver failure (p = 0.01) were independent risk factors for late death (after 3 months). CONCLUSION: These results underscore the importance of adequate recipient selection and recipient/donor matching for short- and long-term survival after primary heart 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 (TNF alpha), 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.

Measures to control blood activation during assisted circulation.

Major improvements in heart assist devices have allowed prolonged mechanical circulatory support with successful subsequent weaning or heart transplantation. The contact of blood with biomaterials used in life-sustaining devices and numerous biomaterial-independent factors elicit a systemic inflammatory response, which involves activation of various plasma protein systems and blood cells. Prolonged mechanical circulatory support elicits a systemic inflammatory response and hemostatic perturbations similar to that reported during cardiopulmonary bypass. However, in the setting of prolonged assistance, time has a complex and ill-known influence on blood activation. Methods to reduce blood activation during prolonged assisted circulation are derived from cardiopulmonary bypass investigations. Improving the biocompatibility of artificial devices can be achieved either by biomaterial surface modifications, by inhibition of biologic cascades leading to blood activation, or by controlling end points of biologic cascades. However, the necessity to respect the integrity of the organism during prolonged assistance precludes most systemic interventions and limits the control of blood activation to the area of the device.

Heparin coating of extracorporeal circuits inhibits contact activation during cardiac operations.

OBJECTIVE: Heparin coating reduces complement activation on the surface of extracorporeal circuits. In this study we investigated its effect on activation of the contact system in 30 patients undergoing coronary artery bypass grafting with the use of a heparin-coated (Duraflo II, Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.; n = 15) or an uncoated extracorporeal circuit (n = 15). METHODS: Plasma markers that reflect activation of contact (kallikrein-C1-inhibitor complexes), coagulation (prothrombin fragments F1 + 2), or fibrinolytic (plasmin-alpha 2-antiplasmin complexes) systems were determined before and during the operation. The generation of kallikrein-C1-inhibitor complexes was reduced by 62% (p = 0.06) after the onset of cardiopulmonary bypass and by 43% (p = 0.026) after the cessation of bypass in the group in which a heparin-coated circuit was used compared with the group in which the circuit was uncoated. Generation was reduced by 58% (p = 0.06) when the ratio of kallikrein-C1-inhibitor to prekallikrein after onset of bypass was considered. We detected significant increases in F1 + 2 levels in both groups and increases in plasmin-alpha 2-antiplasmin complexes in the heparin-coated group at cessation of bypass, but no intergroup differences were observed. Thus use of heparin-coated extracorporeal circuits during cardiac operations reduces formation of kallikrein-C1-inhibitor complexes when compared with use of uncoated circuits. The heparin coating is not accompanied by similar reductions in coagulation or fibrinolysis, suggesting that thrombin and plasmin formation during cardiopulmonary bypass occurs mainly independently of the contact system activation.

Clinical evaluation of Duraflo II heparin treated extracorporeal circulation circuits (2nd version). The European Working Group on heparin coated extracorporeal circulation circuits.

OBJECTIVES: To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out. METHODS: In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II). RESULTS: Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (> 24 h) was significantly lower when they received heparin treated circuits versus controls. CONCLUSION: These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.