León Eijsman

Activation of the Complement System During and After Cardiopulmonary Bypass Surgery Postsurgery Activation Involves C-Reactive Protein and Is Associated With Postoperative Arrhythmia

BACKGROUNDnComplement activation during cardiopulmonary bypass (CPB) surgery is considered to result from interaction of blood with the extracorporeal circuit. We investigated whether additional mechanisms may contribute to complement activation during and after CPB and, in particular, focused on a possible role of the acute-phase protein C-reactive protein (CRP).nnnMETHODS AND RESULTSnIn 19 patients enrolled for myocardial revascularization, perioperative and postoperative levels of complement activation products, interleukin-6 (IL-6), CRP, and complement-CRP complexes, reflecting CRP-mediated complement activation in vivo, were measured and related to clinical symptoms. A biphasic activation of complement was observed. The ratio between the areas under the curve of perioperative and postoperative C3b/c and C4b/c were 3:2 and 1:46, respectively. IL-6 levels reached a maximum at 6 hours post-surgery. CRP levels peaked on the second postoperative day. Each complement-CRP complex had peak levels on the second or third postoperative day. By multivariate analysis, maximum levels of CRP on the second postoperative day were mainly explained by C4b/c levels after protamine administration, leukocyte count on the second postoperative day, and preoperative levels of CRP. Peak levels of C4b/c after protamine administration (P=.0073) and on the second postoperative day correlated with the occurrence of arrhythmia on the same day (P=.0065).nnnCONCLUSIONSnCardiac surgery with CPB causes a biphasic complement activation. The first phase occurs during CPB and results from the interaction of blood with the extracorporeal circuit. The second phase, which occurs during the first 5 days after surgery, involves CRP, is related to baseline CRP levels, and is associated with clinical symptoms such as arrhythmia.

Platelet preservation during cardiopulmonary bypass with aprotinin.

A remarkable reduction of postoperative blood loss after cardiopulmonary bypass (CPB) has been achieved by prophylactic treatment with the proteinase inhibitor aprotinin. To reveal the mode of action of aprotinin, 23 CPB patients were randomised for aprotinin (2 x 10(6) KIU in the pump prime) or placebo treatment during CPB. Blood samples were collected before and during operation. Blood loss and blood requirements were 50% lower in the aprotinin treated patients than in the untreated patients. The adhesive capacity of platelets assessed by the amount of platelet membrane glycoprotein Ib (GP Ib) decreased by 50% in the untreated patients within 5 min of CPB and remained low during CPB, whereas GP Ib did not decrease in the aprotinin treated patients. Fibrinogen degradation products indicating plasmin activity could only be measured after 30 min of CPB in the untreated, but not in the aprotinin treated patients. The kallikrein inhibiting capacity was 34% decreased in the untreated patients within 5 min of CPB, while it increased by 84% and remained high during CPB in the aprotinin treated patients. Our results demonstrate that the improved haemostasis during and after CPB in patients treated with aprotinin can be attributed to the preserved adhesive capacity of platelets. It remains to be found whether aprotinin has a primary effect on platelets or a secondary effect by plasmin or kallikrein inhibition.

Reduced renal failure following thoracoabdominal aortic aneurysm repair by selective perfusion

OBJECTIVESnRenal failure and visceral ischemia are feared complications following thoracoabdominal aortic aneurysm (TAAA) repair, significantly contributing to mortality. This prospective study describes volume- and pressure-controlled perfusion of the renal and visceral arteries during TAAA surgery.nnnMETHODSnIn 73 consecutive patients (mean age 59 years), TAAA repair (27 type I, 28 type II, 8 type III and 10 type IV) was performed, using retrograde and selective organ perfusion. Sixteen patients had impaired renal function with blood creatinine higher than 100 mmol/l. During the thoracic part of the procedure, the mean distal aortic pressure was kept above 60 mm Hg by means of left-heart bypass. After opening the abdominal aorta, the renal and visceral arteries were individually perfused by means of perfusion catheters (9 French) in the first 33 patients (group I). Volume flow through each catheter was assessed with ultrasound flow meters and maintained at least at 60 ml/min. In addition to volume flow measurements, catheters with pressure sensors were used in the last 40 patients (group II), allowing pressure-controlled selective perfusion. The extent of the aneurysm was comparable in both groups.nnnRESULTSnMean cross-clamp time for the thoracic part was 46 min, including proximal anastomosis and reattachment of intercostal arteries. Mean cross-clamp time for the abdominal part was 74 min, including re-implantation of intestinal and renal arteries and selective dacron grafts to the celiac-axis arteries (n = 5), superior mesenteric arteries (n = 8) and renal arteries (n = 25), through which the catheters guaranteed continuous perfusion during the time the anastomosis was performed. Urine output was uninterrupted in all patients, irrespective of cross-clamp time. In group I, one patient (3%) developed renal failure and three patients (9%) required temporary peritoneal dialysis. In group II, no patients developed renal failure and two patients (5%) required temporary peritoneal dialysis. Thirteen patients with pre-existing renal impairment did not deteriorate. No patients developed visceral ischemia or multiple-organ failure. Total in-hospital mortality was 6/73 (8%) and was related to cardiopulmonary complications.nnnCONCLUSIONSnRenal and visceral ischemia can be reduced significantly by continuous perfusion during cross-clamping in TAAA repair. Not only sufficient volume flow but also adequate arterial pressure appears to be essential in maintaining renal function.

Clinical evaluation of duraflo II heparin treated extracorporeal circulation circuits (2nd version): The European working group on heparin coated extracorporeal circulation circuits

OBJECTIVESnTo 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.nnnMETHODSnIn 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).nnnRESULTSnSignificant 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.nnnCONCLUSIONnThese 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.

Generation of platelet-derived microparticles in patients undergoing cardiac surgery is not affected by complement activation

OBJECTIVEnThe mechanisms causing the presence of platelet-derived microparticles in the circulation are unknown. In vitro platelets release platelet-derived microparticles in response to complement activation. This study evaluates the relationship between complement activation and levels of circulating platelet-derived microparticles in patients undergoing cardiac surgery.nnnMETHODSnProspectively, 71 patients were included who underwent elective coronary artery bypass grafting with cardiopulmonary bypass. The patients were randomly allocated to one of the 3 groups: uncoated oxygenator, UnModified Surface (n = 25) or oxygenator coated with either BioPassive Surface (n = 25) or BioActive Surface (n = 21). Platelet-derived microparticles and terminal complement complexes were determined before bypass and after induction of anesthesia, 15 minutes after the start of cardiopulmonary bypass, at the end of cardiopulmonary bypass, and 30 minutes after administration of protamine sulfate.nnnRESULTSnDemographic and cardiopulmonary bypass data were similar for the 3 groups. At the end of cardiopulmonary bypass, platelet-derived microparticle numbers were decreased in all 3 groups. No significant differences were observed among the groups at any sampling point. At the end of cardiopulmonary bypass, terminal complement complex concentrations were increased in all groups (P <.001), and significant differences among the groups were present (P =.002).nnnCONCLUSIONSnDespite significant complement activation, no increase in numbers of circulating platelet-derived microparticles was found in the systemic blood of patients undergoing cardiac surgery with cardiopulmonary bypass. Thus complement activation in vivo does not necessarily affect generation of platelet-derived microparticles.

Topical vascular endothelial growth factor in rabbit tracheal surgery: comparative effect on healing using various reconstruction materials and intraluminal stents

OBJECTIVESnThe effect of topical vascular endothelial growth factor (VEGF) on post-surgical tracheal healing using various reconstruction materials was studied, with particular regard to prevention of granulation tissue or fibrosis.nnnMETHODSnTwenty-four New Zealand White rabbits underwent survival surgery using autograft patches (n=6), xenopericardium patches (n=6), intraluminal Palmaz wire stents (n=6), and controls (n=6). Autograft and pericardial half-patches were soaked in topical VEGF (5 microg/ml over 30 min) and saline before reimplantation. Stents and controls received circumferential injections of VEGF and saline in the tracheal wall. At 1-4 months postoperatively, specimens of sacrificed animals were stained with anti-VEGF antibody, followed by morphological and immunohistochemical examination.nnnRESULTSnRabbits with autografts and controls fared well until planned sacrifice. After xenopericardium repair, obstructive intraluminal granulation tissue led to early sacrifice in three rabbits. Stent insertion led to earlier death from airway obstruction in all six rabbits. Topical VEGF reduced granulation tissue after pericardial repair and fibrosis in all repairs except in stents. Remarkably, VEGF-pretreated half-patches and saline half-patches stained similarly high for VEGF, suggesting also local production of VEGF, probably in plasmacells, and in submucosal glands.nnnCONCLUSIONSnAutograft repair induces the least granulation tissue and fibrosis, and the best healing pattern. Stents rapidly induced critical airway obstruction, unhindered by VEGF, leading to premature death. Tracheal pretreatment with topical VEGF reduces postoperative fibrosis after autograft and pericardial patch repairs, and reduces granulation tissue after xenopericardium repair. In time, VEGF is probably locally produced, although its potential role in tracheal healing remains to be established.

Adhesion of thrombotic components to the surface of a clinically used oxygenator is not affected by Trillium coating.

The Trillium® coating is designed to minimize adsorption of protein and the attachment of cells and other particles. The present study was undertaken to investigate the effect of surface coating on the adhesion of thrombotic components (activated platelets, white blood cells and fibrin) to the surface of a clinically used oxygenator. Twenty patients undergoing elective coronary artery bypass grafting (CABG) were randomized to one of the two oxygenator groups: non-coated (NC, n=10) or Trillium®-coated (TC, n=10). Platelet and white blood cell counts and factor XIIa concentrations were determined prior to the induction of anesthesia and at the end of cardiopulmonary bypass (CPB). Binding of activated platelets, white blood cells and fibrin to the artificial surfaces was quantified by means of antibody binding and histological validation was achieved by scanning electron microscopy. Patient demographic and CPB data were similar for the two groups. No significant differences between the groups were found for any of the tested thrombotic components. However, observations from our scanning electron microscopy suggested a release of formed particles from the Trillium®-coated surface. Primary adhesion of activated platelets, white blood cells and fibrin to the artificial surface of the venous blood inlet from an oxygenator is not affected by the Trillium® surface coating under conditions of full systemic heparinization.