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A heparin-coated circuit reduces complement activation and the release of leukocyte inflammatory mediators during extracorporeal circulation in a rabbit.

Heparin coating modifies complement activation during extracorporeal circulation much more effectively than systemically administered heparin. This rabbit study was undertaken to address possible mechanisms responsible for this difference. We evaluated the effect of heparin coating on complement activation and subsequently the release of leukocyte inflammatory mediators during extracorporeal circulation through a simplified circuit. We found in the heparin-coated group a significantly reduced complement hemolytic activity (CH50), remaining higher leukocyte numbers, significantly decreased release of beta-glucuronidase, and most strikingly a complete prevention of tumor necrosis factor (TNF) formation. The significantly reduced CH50 activity in the heparin-coated groups indicates the reduction of one or more native classical complement products. This could be explained by the absorption of complement components by the circuit, which results in reduced activity of the complement cascade. We conclude therefore that heparin coating reduces complement activation and consequently reduces the release of leukocyte inflammatory mediators.

Animals↗

[Changes in hemostasis at aortic surgery under conditions of extracorporeal circulation].

This paper describes hemostatic changes in patients who had undergone aortic surgery under conditions of extracorporeal circulation. The changes in the hemostatic system are marked by the thrombophilic condition made up for activation ox blood fibrinolytic activity in the preoperative period. The basic amount of blood loss falls within the first 6 hours after operation. Prolonged hypothermic extracorporeal circulation and the high intraoperative blood loss (over 35 ml/kg bw) lead to an appreciable decrease in antithrombin III and protein C activity which results in activation of disseminated intravascular blood coagulation in the early postoperative period and ineffectiveness of heparin therapy. Secondary hyperfibrinolysis together with combined thrombocytopenia and platelet dysfunction are the basic causes of higher than usual bleeding in patients after aortic surgery under conditions of extracorporeal circulation.

Antithrombin III↗

[Coronary surgery without extracorporeal circulation: 5-year experience].

INTRODUCTION: Coronary surgery without extracorporeal circulation is now an accepted technique of myocardial revascularization. A progressive increase in operations has recently been observed. OBJECTIVE: We report our total experience with this technique in a consecutive series of patients operated on since 1991. This series is compared with other series of patients who underwent coronary surgery using cardiopulmonary bypass. PATIENTS AND METHODS: From December 1991 to July 1996, thirty patients underwent myocardial revascularization without cardiopulmonary bypass through median sternotomy at our institution. This group was retrospectively compared with 22 patients who received isolated coronary artery bypass grafting with cardiopulmonary bypass (excluding reoperations) during the same period of time. RESULTS: There were two hospital deaths and one case of myocardial infarction during the early postoperative period which required urgent reintervention. There were two variables showing a statistically significant difference between the groups with and without cardiopulmonary bypass. Incidence of non-fatal preoperative myocardial infarction increased (53% vs 23%), whereas minor mechanical ventilation time was reported (7 +/- 5 vs 14 +/- 9 h) in the group without cardiopulmonary bypass. Follow-up (1 to 55 months after operation, mean 29 months) was completed. There were no cardiac-related deaths. No return of angina nor any new myocardial infarctions were recorded. New myocardial revascularizations were not necessary. CONCLUSIONS: Myocardial revascularization without extracorporeal circulation obtained good results that were similar to conventional procedures and were cost-effective.

Adult↗

[Silicone embolism, fat embolism, and fibrin thrombosis in dogs after extracorporeal circulation using a bubble-oxygenator (author's transl)].

Following extracorporeal circulation with a bubble oxygenator (Rygg-Kyvsgaard) silicone emboli were found in the brain-and-kidney-capillaries of all dogs evaluated. There was no obvious correlation between intensity of silicone embolism and pump time. No cellular reaction was seen around the anti-foam agent. Occasionally single small areas of embolic brain damage were found. During extracorporeal circulation and within a recovery period up to one hour no silicone excretion through the kidneys could be demonstrated. Systemic fat embolism occurred less frequent than previously reported. Use of a filter in the cardiotomy suction line reduced its intensity further. In neither of the various organs examined, disseminated intravascular thrombosis could be found.

Animals↗

The monitoring of heparin activity during extracorporeal circulation.

Heparin activity was assessed in 11 patients who underwent extracorporeal circulation for open-heart surgery. The activated partial thromboplastin time (A-PTT), thrombin time, protamine sulphate titration and factor Xa inhibition assay were used. The patients received heparin 3 mg/kg body weight, and 20 mg/450 ml blood was added to the pump. When the operative procedure was extended beyond 100 minutes patients received an additional 1,5 mg heparin/kg body weight. Protamine sulphate in a dose of 1,5 mg/1 mg heparin, was given to neutralize the heparin activity. The A-PTT was the easiest test which gave reliable results. The factor Xa inhibition assay measured heparin levels most precisely and mirrored the A-PTT results in all but one instance. These results indicate that the protocol employed produced adequate anticoagulation for the bypass procedure in all the patients. Protamine sulphate failed to neutralize heparin adequately after bypass in the 3 patients who received additional heparin during the surgical procedure. The monitoring of heparin activity during and after extracorporeal circulation is a desirable addition to open-heart surgical treatment.

Blood Coagulation Tests↗

Extracorporeal circulation, hemocompatibility, and biomaterials.

BACKGROUND: Performance of a majority of cardiac surgical procedures requires the use of extracorporeal circulation. Contact of the patients' blood with the nonendothelial surface of the cardiopulmonary bypass circuit is responsible for several, potentially harmful systemic reactions. METHODS: The patients' response to extracorporeal circulation is reviewed briefly. The interactions between patient and circuit are discussed not only as they relate to blood-material contact, but also from a mechanical and rheologic standpoint. The theoretic benefits of the newer, more hemocompatible materials are presented, along with a review of published clinical experience with heparinized cardiopulmonary bypass circuits. RESULTS: The response to extracorporeal circulation extends far beyond a simple derangement of hemostasis. This inflammatory response is strongly influenced by the rheologic design of the circuit and by the physical and chemical properties of the surface. Heparinized circuits decrease inflammation, but the clinical benefits of this reduction remain unclear, except for extended cardiopulmonary support. The safe use of these circuits requires full heparinization and does not reduce allogeneic transfusions. CONCLUSIONS: Clinicians are still in the search of the ideal material and the ideal extracorporeal circuit design. Newer, heparinized materials offer real but limited clinical benefits.

Biocompatible Materials↗

[Clinical study of serum enzyme and metabolic changes after extracorporeal circulation--comparison with the surgery of aortic aneurysm].

The changes of serum enzyme and metabolism were studied by comparing the serial change among three groups. The first group consisted of twenty seven patients treated by surgery under extracorporeal circulation. The second group of ten patients of thoracic aortic aneurysm treated under temporary bypass and the third group of nineteen patients of abdominal aortic aneurysm under aortic cross clamp. The following results were obtained: The enzyme of serum GOT, LDH and CPK increased postoperatively in the all groups, the changes after surgery being greater in the group 1 than the other groups. The metabolism of lactic acid and glycolipid was depressed in the group 1 higher than the other groups. The tissue injury of total body after surgery with extracorporeal circulation was greater than the other groups without extracorporeal circulation. And these results suggest the necessary of improvement of circuit and perfusion technique of extracorporeal circulation.

Alanine Transaminase↗

Cerebral microembolus generation in different extracorporeal circulation systems.

Microemboli generated during extracorporeal circulation (ECC) are likely to induce neurological sequelae. This study examines whether the choice of a distinct type of ECC can reduce intracerebral emboli counts. Middle cerebral artery blood flow during coronary artery bypass grafting was monitored continuously by transcranial Doppler ultrasound in 45 patients. The ECC systems used were a roller pump (n = 16), a centrifugal pump (n = 18) and a combination of centrifugal pump and heparin-coated ECC system (n = 11). Patients' characteristics as well as surgical and anesthesiological procedure did not differ between the groups. Total counts did not differ significantly between the three groups. Intraoperative events in individual patients may lead to massive embolus generation overcoming positive properties of a distinct ECC system.

Aged↗

[The behaviour of the granular alveocytes in chronic pulmonary congestion, pulmonary fibrosis and after extracorporeal circulation (author's transl)].

The granular alveocytes, known to be the site of the production of the surfactant, undergo characteristic changes following chronic pulmonary congestion and the succeeding fibrosis, and after extracorporeal circulation. Congestion is accompanied by cell edema and the breakdown of the lamellar bodies. With fibrosis the cells are shrunken and present with little if any lysosomes. The nuclei are pyknotic or demonstrate karyolysis. Vacuolar degeneration of the lamellar bodies and progressive degeneration of the mitochondria are observed. The extracorporeal circulation damages many granular alveocytes. The degree of damage correlates with the duration of the cardiopulmonary bypass and with the degree of the prepump pathological changes present in the lungs. On the other and the extracorporeal circulation induces in the intact cells enhanced surfactant production, during which the different developmental stages of the lamellar body increasingly accumulate within the cell. In conclusion, pulmonary congestion and fibrosis reduce the activity of the granular alveocytes. The extracorporeal circulation enhances structurally favourable conditions in the granular alveocytes for the increased release of the surfactant in the immediate post-operative phase - a process which could be regarded as an autoregulatory mechanism.

Adult↗

Selective removal of human serum amyloid P component from rat blood by use of an immunoaffinity membrane in an extracorporeal circulation system.

We examined the suitability of an immunoaffinity membrane (IAM) bearing specific antibody as a ligand for removing human serum amyloid P component (hSAP) from blood passed through a simple extracorporeal circulation system established in rats. The specific antibody was the most effective of the various ligands tested for removing hSAP from human blood. To determine the value of the hSAP in human or rat plasma, we also developed a simple ELISA. In the rat extracorporeal circulation system, the hSAP level in the inlet blood to the IAM module decreased to 49% of the initial concentration within 60 min. In contrast, the hSAP remained at the initial concentration throughout the study in the module without the IAM. The use of this extracorporeal circulation system in this case allows preclinical evaluation of the ex vivo removal of a human plasma component in an animal model. Biocompatibility of the IAM was also examined. No change in blood cell counts or activation of the coagulation system occurred after contact with the IAM. Non-specific adsorption was not observed, since there was no statistically significant difference in IgG, complement C3, or albumin level between the pre- and post-treatment with this module. The immunological effects of the IAM were also examined using this system. Four weeks after the termination of the extracorporeal circulation, the rats examined showed no detectable antibody titer to the ligand.

Adsorption↗

Myocardial Revascularization in Patients 70 Years of Age and Older Without the Use of Extracorporeal Circulation.

Myocardial revascularization in elderly patients (i.e., over 70 years of age) is associated with higher incidence of morbidity and mortality compared with younger patients. We herein report our experience on myocardial revascularization in the elderly comparing the results between 2 groups; one operated on with the aid of cardiopulmonary bypass and the other group in whom extracorporeal circulation was not used. The records of 265 elderly patients ( at or above 70 yrs) undergoing myocardial revascularization were prospectively analyzed between January 1994 and December 1995. Mean age was 74 Â+/- 6 years (range 70-95 yrs), with 83 (31.3%) females and 182 (68.7%) males. The following were the preoperative diagnoses: chronic ischemia and angina (186 patients), reoperation (28 patients), unstable angina (26 patients), failed angioplasty (13 patients), post-thrombolytic therapy (7 patients), cardiogenic shock (2 patients), evolving myocardial infarction (2 patients), and aortic dissection (1 patient). Extracorporeal circulation was used in 204 (76.9%) patients (Group I) and no extracorporeal circulation was used in 61 (23.1%) patients (Group II). The overall mortality was 6.4%, with 7.8% (16/204) in Group I and 1.6% (1/61) in Group II. Hospital stay was 11.4 days in Group I and 7.1 in Group II. Transfusion requirements were 1.4 and 0.6 units for Groups I and II, respectively. The use of extracorporeal circulation in the elderly is a major cause of morbidity and mortality following myocardial revascularization. Whenever possible, myocardial revascularization in the elderly should be performed without the use of extracorporeal circulation.

Journal Article↗

Nitric oxide inhibits neutrophil adhesion during experimental extracorporeal circulation.

BACKGROUND: Myocardial and pulmonary injuries often occur after cardiopulmonary bypass, mediated in part by neutrophil activation and adhesion to endothelial cells. The effects of nitric oxide (NO) administration on neutrophil adhesion to endothelial cells after simulated extracorporeal circulation were investigated. METHODS: Two identical extracorporeal circulation circuits were primed with fresh human blood and circulated for 2 h at 37 degrees C. Nitric oxide at a 40-ppm concentration was added to one of the oxygenators in each pair. Neutrophil CD11b/CD18 expression and their adhesion to human umbilical vein endothelial cell monolayers were assayed in leukocytes isolated from samples drawn from the circuit 30, 60, 90, and 120 min after circulation began. In another series of experiments, blocking monoclonal antibodies to both neutrophil CD11b and CD18 were incubated with polymorphonuclear leukocytes after removal from the circuit before the adhesion assay. RESULTS: After 60 min of circulation, the neutrophils from NO-treated circuits showed significantly reduced CD11b/CD18 surface expression compared with the control group. There was also a significant reduction in neutrophil-endothelial adhesion in the NO group after 120 min of circulation. Monoclonal antibodies to both CD11b and CD18 significantly inhibited the adhesion of polymorphonuclear leukocytes at endothelial cells after 120 min of circulation. CONCLUSIONS: These results confirm that neutrophil activation occurs during cardiopulmonary bypass. The addition of NO to the circuits of extracorporeal circulation significantly affects neutrophil adhesion to endothelial cells.

Adult↗

Ultrasonic pulsed Doppler blood flowmeter for use in extracorporeal circulation.

In cardiac surgeries, it is frequently necessary to make the external blood circulation and oxygenation artificially. This procedure is called extracorporeal circulation (EC) or heart-lung bypass. During EC, one of the most important parameters, which demands continuous monitoring, is the blood flow. In many cases, the blood flow is estimated by the pump velocity (in roller pumps) or measured with transducers based on electromagnetic methods (in centrifugal pumps). This article presents an ultrasonic Doppler blood flowmeter to be used in the arterial line of an extracorporeal circulation system. The ultrasonic probe is coupled to a half-inch tube connector of the extracorporeal arterial line, is not disposable, and does not need sterilization. The developed flowmeter revealed itself to be efficient and reliable and can be inserted in a closed-loop pump controller system or be used as stand-alone equipment.

Blood Flow Velocity↗

Renal pathomorphology and histochemistry in dog after hemodilution as well as after administration of full blood in extracorporeal circulation in dog.

Dog kidneys were studied morphologically and histochemically after hemodilution to a 10--20% hematocrict value and transfusion of whole blood under conditions of extracorporeal circulation ensuring constant (linear) flow. Marked interstitial edema in the dog kidneys after hemodilution was the most pronounced alteration, attributed to disorders in the capillary circulation depending upon the apparatus employed. This conclusion was supported by similar changes in animals subjected to various degrees of hemodilution. Widening of the glomerular space and compression of renal tubules were the direct consequences of interstitial edema. Histochemical reactions revealed damage of the cell membranes. Swelling of the ergastoplasm and lysosomes was interpreted as secondary to disorders in circulation of tissue fluid. The least pronounced changes concerned the mitochondria. After extracorporeal circulation with whole blood, thrombi and fat emboli were observed in the blood vessels of the renal glomeruli, attributable to damage of blood in the extracorporeal circulation apparatus.

Adenosine Triphosphatases↗

[Effect of a preoperative separation of platelets on the postoperative blood loss subsequent to extracorporeal circulation in open heart surgery (author's transl)].

After operations with extracorporeal circulation there is a risk of clotting disorders, due to traumatisation of blood. The extent of cell damage are shown, in particular, by qualitative and quantitative impairment of platelet function. The clinical application of modern blood processors offer the possibility of selecting platelets from patients blood in the immediate preoperative period. Open heart operations were preceded by separation of platelets in 17 patients using a Haemonetics blood processor. After a postoperative retransfusion of the platelets an evident improvement in platelet function and a significant decrease in the predisposition to bleeding was demonstrated in the further postoperative period. During and after extracorporeal circulation the extent of microembolisation was registered by screen filtration pressure. In the clinical experiments, regularly, there is a significant increase of screen filtration pressure in the immediate postoperative period. These reactions were not seen in patients in whom preoperative separation of platelets was carried out. The most important clinical advantage of preoperative plateletpheresis consists in a significant decrease of postoperative blood loss. In particular the development of postperfusion lung will be prevented.

Blood Platelets↗

Cardiopulmonary function during and after prolonged extracorporeal circulation with membrane oxygenators in dogs.

Prolonged veno-arterial partial extracorporeal circulation using membrane oxygenator was performed in 19 alert dogs. Investigations of alterations in the corpuscular elements of the blood during the perfusion showed 89 mg% as the highest value of free haemoglobin. A significant decrease in the platelet count during the first two hours of bypass to a value of about 100 000/mm3 was found. Measurements of lung and heart functions did not reveal any significant differences between the baseline values and those obtained after 24 hours' bypass and again after three months' observation. Microscopic examination of the lungs and hearts only showed moderate focal alveolar oedema in the dogs killed immediately after 24 hours' bypass. These alterations could be explained as a consequence of the extracorporeal circulation. No changes were found at the microscopic examination of the lungs and hearts three months later. By haemodilution technique, the dogs suffered from severe universal oedema after a few hours of bypass and the perfusion time in these experiments did not exceed 13 hours. The observation that 24 hours of partial veno-arterial bypass using membrane oxygenators in healthy dogs causes only minor changes in heart and lung function and in lung histology might explain the possibility of using such oxygenators in prolonged perfusions.

Animals↗

Management of a giant intracranial aneurysm using surface-heparinized extracorporeal circulation and controlled deep hypothermic low flow perfusion. A case report.

Extracorporeal circulation with controlled hypothermic low flow perfusion was introduced during the surgical treatment of a patient with a giant intracranial aneurysm of the anterior communicating artery. Heparin-coated equipment (Carmeda Bio-Active Surface; CBAS) was utilized, thus reducing the need for systemic heparinization. Direct cannulation of the right atrium and aorta was established through thoracotomy. Blood flow through the circuit was kept at 4.5 l/min during normothermia. Core cooling, in combination with external surface cooling, was performed for 30 min to a temperature of 18 degrees C (nasopharynx). During a period of 25 min, the time for surgical repair of the aneurysm, blood flow was minimized to 0.4 l.min-1, equilibrating central and peripheral blood pressures to approximately 5-10 mmHg (0.65-1.3 kPa). Reperfusion was started immediately after the low flow period concomitantly with rewarming, aiming at a temperature of 36 degrees C following 150 min. The patient could be weaned off the extracorporeal circulation with minimal inotropic support. The postoperative course was uneventful apart from a left-sided hemiparesis, probably due to an infarction in the area of the right pericallosal artery (A2). The patient was weaned off the ventilator after 6 days. He recovered and the hemiparesis regressed slowly.

Aged↗

[Antibiotic concentration during extracorporeal circulation (author's transl)].

In open surgery, ampicillin (Solcillin) or cephacetrile (Celtol), 2 g for patients weighing 20 kg or more, and 1 g for those below 20 kg, was administered, and the antibiotic concentrations in blood and urine were estimated during extracorporeal circulation, from the time of operation to the admission in an intensive care unit (Group A). In other group, a total circulation volume of 0.3 mg/ml of the antibiotic was administered, based on body weight of patients and priming volumes (Group B). In Group A, blood concentration of antibiotics was so variable that it was difficult to decide additional dosage. In Group B, comparatively definite concentrations were estimated in each case. In extracorporeal circulation for a long time, it is preferable to maintain the blood concentration of antibiotic at 50 micrograms/ml, by additional antibiotic administration 90 approximately 120 minutes after the beginning of the extracorporeal circulation. In patients with preoperative subacute bacterial endocarditis, the blood concentration should be kept over 100 micrograms/ml during extracorporeal circulation.

Adolescent↗