Mitochondrial complex I defect resulting from exercise-induced lower limb ischemia in patients with peripheral arterial disease.

This study aims to compare the structural and mitochondrial alterations between muscle segments affected by exercise-induced ischemia and segments of the same muscle without ischemia, in the same subject. In a prospective analysis, 34 patients presenting either peripheral arterial disease or chronic coronary syndrome without any evidence of peripheral arterial disease were eligible for inclusion based on findings indicating a need for either a femoro-popliteal bypass or a saphenous harvesting for coronary bypass. Before surgery, we assessed the level of exercise-induced ischemia in proximal and distal sections of the thigh by the measurement of transcutaneous oxygen pressure during an exercise treadmill test. Distal and proximal biopsies of the sartorius muscle were procured during vascular surgical procedures to assess mitochondrial function and morphometric parameters of the sartorius myofibers. Comparisons were made between the distal and proximal biopsies, with respect to these parameters. Thirteen of the study patients that initially presented with peripheral arterial disease had evidence of an isolated distal thigh exercise-induced ischemia, associated with a 35% decrease in the mitochondrial complex I enzymatic activity in the distal muscle biopsy. This defect was also associated with a decreased expression of the manganese superoxide dismutase enzyme and with alterations of the shapes of the myofibers. No functional or structural alterations were observed in the patients with coronary syndrome. We validated a specific model ischemia in peripheral arterial disease characterized by muscular alterations. This "Distal-Proximal-Sartorius Model" would be promising to explore the physiopathological consequences specific to chronic ischemia. NEW & NOTEWORTHY We compared proximal versus distal biopsies of the sartorius muscle in patients with superficial femoral artery stenosis or occlusion and proof of, distal only, regional blood flow impairment with exercise oximetry. We identified a decrease in the mitochondrial complex I enzymatic activity and antioxidant system impairment at the distal level only. We validate a model to explore the physiopathological consequences of chronic muscle ischemia.

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. METHODS: Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. RESULTS: The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. CONCLUSIONS: Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers.

Increasing mean arterial pressure during cardiac surgery does not reduce the rate of postoperative acute kidney injury.

INTRODUCTION: We hypothesized that the optimization of renal haemodynamics by maintaining a high level of mean arterial blood pressure (MAP) during cardiopulmonary bypass (CPB) could reduce the rate of acute kidney injury (AKI) in high-risk patients. METHODS: In this randomized, controlled study, we enrolled 300 patients scheduled for elective cardiac surgery under cardiopulmonary bypass. All had known risk factors of AKI: serum creatinine clearance between 30 and 60 ml/min for 1.73 m(2) or two factors among the following: age >60 years, diabetes mellitus, diffuse atherosclerosis. After a standardized fluid loading, the MAP was maintained between 75-85 mmHg during CPB with norepinephrine (High Pressure, n=147) versus 50-60 mmHg in the Control (n=145). AKI was defined by a 30% increased of serum creatinine (sCr). We further tested others definitions for AKI: RIFLE classification, 50% rise of sCr and the need for haemodialysis. RESULTS: The pressure endpoints were achieved in both the High Pressure (79 ± 6 mmHg) and the Control groups (60 ± 6 mmHg; p<0.001). The rate of AKI did not differ by group (17% vs. 17%; p=1), whatever the criteria used for AKI. The length of stay in hospital (9.5 days [7.9-11.2] vs. 8.2 [7.1-9.4]) and the rate of death at day 28 (2.1% vs. 3.4%) and at six months (3.4% vs. 4.8%) did not differ between the groups. CONCLUSION: Maintaining a high level of MAP (on average) during normothermic CPB does not reduce the risk of postoperative AKI. It does not alter the length of hospital stay or the mortality rate.

[National survey on short-term circulatory and/or respiratory support in 2009]. / Enquête nationale sur l'assistance circulatoire et respiratoire de courte durée en 2009.

OBJECTIVE: Indications for short-term circulatory and/or respiratory support (STCRS) increased during the last years. The goal of this survey was to characterize this activity in France in 2009. STUDY DESIGN: Observational retrospective pluricentral. MATERIAL AND METHODS: Each center of cardiothoracic surgery received a questionnaire validated by the Société française de perfusion about the activity, materials and organization used for STCRS. Data were expressed as percentages or median (25-75 percentiles). RESULTS: Forty-one centers on 61 (67%) answered. STCRS was performed respectively by 33 (80.5 %), 36 (87.8 %) and 39 (95.1 %) of centers in 2007, 2008 and 2009 including 10 [4-26], 18 [6-29] and 18 [5-33] cases/center per year. In 2009, types of STCRS installed were veno-arterial in 39 centres (95.1 %), veno-venous in 27 (65.9 %) and Novalung(®) in four (9.8 %), including 18 [5-32], five [2-7] and 15 [1-17] cases respectively. Twenty-nine centers (70.7%) installed STCRS outside the operating theater, and 24 (58.5%) in non-cardiothoracic surgery. A mobile circulatory support unit was created in eight centers (19.5%), however 21 (51.2%) have installed STCRS externally, at distances between 10 [5-55] to 100 [15-200] km, using emergency vehicles in most of the cases (90.5%), but helicopter seldom (19%). CONCLUSION: STCRS has increased over the last few years in France. Externalized activity outside the operating theater was important, time-consuming and used hospital resources therefore modifying the professional activity of perfusionists.

Key role of estrogens and endothelial estrogen receptor α in blood flow-mediated remodeling of resistance arteries.

OBJECTIVE: Flow- (shear stress-)mediated outward remodeling of resistance arteries is involved in collateral growth during postischemic revascularization. As this remodeling is especially important during pregnancy, we hypothesized that estrogens may be involved. A surgical model eliciting a local increase in blood flow in 1 mesenteric resistance artery was used in 3-month-old ovariectomized female rats either treated with 17-ß-estradiol (E2) or left untreated. METHODS AND RESULTS: After 14 days, arterial diameter was greater in high-flow arteries than in normal-flow vessels. An ovariectomy suppressed high-flow remodeling, while E2 restored it. High-flow remodeling was absent in mice lacking the estrogen receptor α but not estrogen receptor ß. The kinetics of inflammatory marker expression, macrophage infiltration, oxidative stress, and metaloproteinases expression were not altered by the absence of E2 after 2 and 4 days, that is, during remodeling. Nevertheless, E2 was required for the increase in endothelial nitric oxide synthase expression and activation at day 4 when diameter expansion occurs. Finally, the impact of E2 on the endothelium appeared crucial for high-flow remodeling, as this E2 action was abrogated in mice lacking endothelial NOS, as well as in Tie2-Cre(+) ERα(f/f) mice. CONCLUSIONS: We demonstrate the essential role of E2 and endothelial estrogen receptor α in flow-mediated remodeling of resistance arteries in vivo.

Increased cerebral blood flow velocities assessed by transcranial Doppler examination is associated with complement activation after cardiopulmonary bypass.

The role of complement activation on the cerebral vasculature after cardiopulmonary bypass (CPB) is unclear. The goal of the study was to assess whether heparin-coated CPB reduces complement activation, and influences cerebral blood flow velocities (CBFV). Twenty-four patients undergoing coronary surgery were randomly allocated to non-coated (NC-group) or heparin-coated (HC-group) CPB. Complement activation was assessed by measuring sC5b-9. Transcranial Doppler (TCD) was performed on middle cerebral arteries before and after CPB. Systolic (SV), diastolic (DV) and mean (MV) CBFV were measured. Significant increase of sC5b-9 (p=0.003) was observed in the NC-group and CBFV increased after CPB (SV by 27%, p=0.05; DV by 40%, p=0.06; MV by 33%, p=0.04) whereas no changes were detected in the HC-group. TCD values were higher in the NC-group than in the HC-group (SV, p=0.04; DV, p=0.03; MV, p=0.03) although cardiac index, systemic vascular resistance, haematocrit and pCO(2) were similar. Postoperative SV, DV and MV were significantly correlated with sC5b-9 (r=0.583, p=0.009; r=0.581, p=0.009; r=0.598, p=0.007, respectively). Increased CBFV after CPB are correlated to the level of complement activation and may be controlled by heparin-coated circuits.

[Incidence and evolution of thrombotic images within the internal jugular vein following Swan-Ganz catheter insertion in cardiac surgery]. / Incidence et évolution des images thrombotiques dans la veine jugulaire interne après cathétérisme de Swan-Ganz en chirurgie cardiaque.

OBJECTIVES: Insertion of Swan-Ganz catheter for a few days may be necessary in cardiac surgery. This study was aimed at determining the incidence and the evolution of thrombotic images within the internal jugular vein as well as assessing their association with the presence of a prolonged fever at postoperative day 7 in the lack of any documented infection. MATERIAL AND METHODS: All the patients undergoing cardiac surgery had a two-dimensional ultrasonography of internal jugular veins preoperatively, at discharge (day 7) and at postoperative day 90 if thrombotic images were seen at day 7. RESULTS: Sleeve-like and compact thrombotic images have been observed in site of venipuncture in 52 patients (70.3%). None had any residual thrombotic image 90 days after the operation. No clinical thromboembolic migration has been observed. There was no statistical association between the presence of a thrombotic image at the ultrasonography and the duration of catheterization. Moreover, there was no association between the anticoagulation before, during and after the surgery and the presence of a thrombotic image. We found a non-significant association between fever at day 7 and the presence of a thrombotic image within the internal jugular vein. CONCLUSION: Thrombotic images in the internal jugular vein after catheterization are frequent and disappear at day 90. The limited sample size of this study does not provide strong evidence of the role of jugular thrombi in the prolongation of fever after cardiac surgery.

Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries.

OBJECTIVE: Notch3, a member of the evolutionary conserved Notch receptor family, is primarily expressed in vascular smooth muscle cells. Genetic studies in human and mice revealed a critical role for Notch3 in the structural integrity of distal resistance arteries by regulating arterial differentiation and postnatal maturation. METHODS AND RESULTS: We investigated the role of Notch3 in vascular tone in small resistance vessels (tail and cerebral arteries) and large (carotid) arteries isolated from Notch3-deficient mice using arteriography. Passive diameter and compliance were unaltered in mutant arteries. Similarly, contractions to phenylephrine, KCl, angiotensin II, and thromboxane A2 as well as dilation to acetylcholine or sodium nitroprusside were unaffected. However, Notch3 deficiency induced a dramatic reduction in pressure-induced myogenic tone associated with a higher flow (shear stress)-mediated dilation in tail and cerebral resistance arteries only. Furthermore, RhoA activity and myosin light chain phosphorylation, measured in pressurized tail arteries, were significantly reduced in Notch3KO mice. Additionally, myogenic tone inhibition by the Rho kinase inhibitor Y27632 was attenuated in mutant tail arteries. CONCLUSIONS: Notch3 plays an important role in the control of vascular mechano-transduction, by modulating the RhoA/Rho kinase pathway, with opposite effects on myogenic tone and flow-mediated dilation in the resistance circulation.

[Long term evolution of chronic constrictive pericarditis. A study of 56 patients]. / Evolution a long terme des péricardites constrictives chroniques. A propos de 56 patients.

OBJECTIVE AND METHOD: We retrospectively analysed 56 consecutive patients with a confirmed diagnosis of chronic constrictive pericarditis over a period of 23 years. The objective was to analyse the evolution of the annual frequency of constrictive pericarditis, its aetiology and to define the prognostic factors for mortality. RESULTS: The annual frequency of constrictive pericarditis has not diminished over the 23 years of this study, remaining at 2.4 cases per year. Cases with a tuberculous origin have diminished progressively, being replaced by complications of cardiac surgery and mediastinal radiotherapy. Pericardectomy was performed in 41 patients and the average follow up was 9.5 +/- 8.6 years. By the end of the study, 34 patients had died (61.8%), 18 from a cardiovascular cause (38.3%). The independent predictive factors for overall mortality were a history of mediastinal radiotherapy, the age, and plasma sodium level. Only the presence of first degree atrio-ventricular block was an independent predictive factor for cardiovascular mortality. In the pericardectomy group, 24 patients died (60%). A history of mediastinal radiotherapy and the presence of pre-operative hyponatraemia were independent predictive factors for overall mortality. CONCLUSION: Constrictive pericarditis remains a serious pathology. Pericardectomy allows a clear functional improvement, but following pericardectomy more than 60% of patients will die within 10 years of the diagnosis being made.

[Inflammatory response and haematological disorders in cardiac surgery: toward a more physiological cardiopulmonary bypass]. / Réponse inflammatoire et perturbations hématologiques en chirurgie cardiaque: vers une circulation extracorporelle plus physiologique.

The systemic inflammatory response in cardiac surgery is closely related to the haemostasis disturbances. It is responsible of a significant morbidity and mortality that was previously suspected to be caused by cardiopulmonary bypass alone. However, it is time now to clearly identify the factors that are material-dependent from that material-independent. From this point of view, off-pump surgery allowed for better comprehension of the multiple sources of the inflammatory response. Numerous pathways are activated, involving complement, platelets, neutrophiles and monocytes. The tissue pathway of the coagulation system, through tissue factor, is of major importance and has to be surgically considered in order to reduce the whole body inflammatory response postoperatively. The quality of the extracorporeal perfusion through its consequences on organ perfusion, particularly in the splanchnic area, also participates to this pathophysiological process. Beyond the progress of technology provided by the industry, particularly the minimally extracorporeal circulation derived from off-pump surgery evolution, the surgical approach is of major importance in the control of the systemic inflammatory response and must not be ignored yet.

The CarboMedics 'Top-Hat' aortic valve prosthesis: short-term results.

BACKGROUND AND AIM OF THE STUDY: The CarboMedics 'Top-Hat' aortic valve prosthesis has been specifically designed for supra-annular implantation. The aim of this study was to assess the safety of implantation of this prosthesis by reporting the short-term results of follow up. METHODS: Between May 1993 and May 1998, 128 patients (mean age 62.5 +/- 9.8 years; range: 22-76 years) received a CarboMedics 'Top-Hat' prosthesis at our institution. Among patients, 55% were in NYHA functional classes III or IV, and 54.7% had an isolated aortic valve replacement. Associated procedures were: coronary artery bypass grafting (25.7%), double valve replacement (17.1%), treatment of ascending aortic aneurysm (4.7%) and miscellaneous (5.5%). Follow up was 100% complete; total cumulative follow up was 265 patient-years (pt-yr) (range: 2-60 months). RESULTS: The overall mortality rate was 1.5% (two deaths). The operative mortality rate was 0.8% (one death); this patient died from neurological complications after operation for aortic dissection. The other patient died on postoperative day 40 from a massive cerebral hemorrhage. Four patients presented thromboembolic events; in all cases these were reversible ischemic neurologic deficits. One patient had a nonstructural deterioration (endocarditis) and required reoperation. Freedom from mortality was 98.3% at five years (linearized rate of 0.75%/pt-yr). Freedom from thromboembolism was 63.1% at five years (linearized rate 1.5%/pt-yr). CONCLUSION: Short-term results with the CarboMedics 'Top-Hat' prosthesis were satisfactory, with low rates of morbidity and mortality. As this prosthesis has demonstrated a good reliability to date, we have continued its implantation in our institution, and long-term follow up will be necessary to confirm these good early results.

Pretreatment with a potassium-channel opener before prolonged cardiac storage: an evaluation in an experimental brain death model.

BACKGROUND: Pretreatment with a potassium-channel opener has been shown to improve functional recovery after long-term cardioplegic arrest. We evaluated whether pretreatment with the potassium-channel opener cromakalim is beneficial in a more clinically relevant experimental model of brain death in the rabbit. METHODS: Four groups of rabbits were studied in a 2 x 2 factorial experiment (n = 8 per group). Rabbits were subjected to a sham operation or 90 minutes of brain death induced by inflating a subdurally placed balloon. Thirty minutes before heart explantation, rabbits received either no pretreatment or an intravenous injection of cromakalim, 30 microg/kg. Hearts then received 5 hours' hypothermic storage in St. Thomas' Hospital solution and were assessed on a buffer-perfused isolated heart preparation. Hemodynamic recovery, coronary flow, and creatine kinase release were determined after 60 minutes of reperfusion. RESULTS: Systolic function and diastolic function were significantly altered in hearts explanted from brain-dead rabbits compared with hearts from rabbits having a sham operation. Cromakalim pretreatment had no significant effect on poststorage systolic or diastolic function of hearts explanted from brain-dead or sham-operation rabbits. Further, cromakalim pretreatment did not affect coronary flow or overall creatine kinase release during reperfusion. CONCLUSIONS; In vivo pretreatment of brain-dead rabbits or anesthetized rabbits with an intravenous injection of cromakalim had no significant effect on functional recovery of or enzymatic release from explanted hearts after 5 hours' hypothermic storage and 60 minutes' reperfusion. These findings underscore the importance of clinically relevant experimental models.

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.

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.

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.