Silicon-carbide coated coronary stents have low platelet and leukocyte adhesion during platelet activation.

BACKGROUND: Stent thrombosis and restenosis are of great clinical significance. We constructed a closed loop in vitro heparinized whole human blood circulation model for testing hemocompatibility of coronary stents. This model allows evaluation of human blood activation by blood-stent interaction in a well-controlled setting. Until now these interactions were studied in the highly coagulable pig coronary artery model. METHODS: We evaluated activation of the coagulation system and blood components by uncoated, heparin-coated, and silicon-carbide coated tantalum stents. The effects, measured by biochemical assays, were compared with stainless-steel stents. Also the inhibitory effect on platelet activation by indomethacin equal to the oral effect of 325 mg acetylsalicylic acid daily, was measured and visualized by scanning electron microscopy. RESULTS: Both activation of the coagulation system and platelets were counteracted by indomethacin, suggesting an important role for platelets in activation of the coagulation system in this model. Despite platelet activation by all stents, the SiC-coated tantalum stent demonstrates a significantly lower GpIIIa receptor-mediated platelet adhesion at the stent surface (21.7 x 10(3) counts per second/mg stent weight) compared to all other stents (stainless-steel 54.0, heparin-coated 95.7 and uncoated 76.2 x 10(3) cps/mg). Also activated leukocytes demonstrated a significantly lower CD11b receptor-mediated adhesion at the SiC-coated stent (37.0 x 10(3) cps/mg) than at the stainless-steel stent (114.5 x 10(3) cps/mg). CONCLUSIONS: Data from this in vitro circulation study show a significantly lower platelet and leukocyte adhesion at the surface of the SiC-coated tantalum stent than at the surface of stainless-steel stents or uncoated and heparin-coated tantalum stents.

Blood damage, platelet and clotting activation during application of radiofrequency or cryoablation catheters: a comparative in vitro study.

During catheter ablation of cardiac tissue, the insulting stimulus may damage and activate the blood. Specifically activation of platelets and the clotting system is a potential risk by their formation of thrombi. In this study the effect of two different techniques, a radiofrequency and a cryo-application procedure, on the activation of platelets and clotting in an in vitro blood circulation model was investigated. The radio-frequency procedure induced significantly more blood cell damage, platelet activation and clotting than did the cryo-application procedure. Macroparticles were circulating in blood after the radiofrequency procedure. In the cryo procedure, blood damage was limited to the frozen blood spherule around the tip of the catheter. It is concluded that at least in those circumstances where blood is directly contacting the tip of the radiofrequency or cryo-application catheter, the latter is more safe with regard to thrombus formation.

Comparison of three plasma expanders used as priming fluids in cardiopulmonary bypass patients.

Ten per cent low molecular weight hydroxyethyl starch is a plasma substitute only recently used as priming solution in an extracorporeal circuit, in contrast to human albumin and gelatin. To evaluate the effect of priming solutions on haemodynamics and colloid osmotic pressure, we studied 36 patients elected for cardiopulmonary bypass (CPB). They were randomly assigned to 2.5% hydroxyethyl starch, 3% gelatin or 4% human albumin priming solution. Total blood loss (perioperative + intensive care unit period) was higher in the gelatin group than in the albumin and hydroxyethyl starch groups. During CPB, the colloid osmotic pressure was best preserved in the gelatin group, although no excessively low colloid osmotic pressures were measured in the other two groups. Due to the extended half-life and the additional postoperative colloid administration, the hydroxyethyl starch group had a higher colloid osmotic pressure in the postoperative phase. We conclude that, next to human albumin, 2.5% hydroxyethyl starch is a safe CPB priming solution additive and is effective as plasma substitute. Its somewhat longer half-life requires adaptation of the routine protocol for transfusion of colloids and blood products.

Hemostatic effects of three colloid plasma substitutes for priming solution in cardiopulmonary bypass.

OBJECTIVE: To evaluate the effects on hemostasis of three different plasma substitutes with special reference to a newly developed hydroxyethyl starch used as priming solution in an extracorporeal circuit as well as peri- and postoperative infusion fluid, we studied 36 patients randomly assigned to one of three groups, undergoing coronary artery bypass grafting. METHODS: The compositions of the priming solutions were: 2.5% hydroxyethyl starch; 3% gelatin; and 4% human albumin. Platelet function tests and clotting assays were performed on blood samples collected during and after cardiopulmonary bypass. RESULTS: We found that plasma von Willebrand Factor remained higher in the human albumin group. Hydroxyethyl starch preserved platelet agglutination as well as human albumin, whereas platelet aggregation induced by adenosine 5'-di phosphate (ADP) proved to be similarly affected during cardiopulmonary bypass in the three study groups. Prolongation of the in vitro bleeding constant during the bypass period and subsequent partial recovery showed an affected platelet function in all groups during cardiopulmonary bypass. The clotting times, activated partial thromboplastin time and prothrombin time were similar in the three groups. Blood loss, peri- and postoperatively, showed also no differences. Hydroxyethyl starch appeared most cost-effective as priming solution in an extracorporeal circuit. CONCLUSIONS: We conclude that, with human albumin the golden standard, 2.5% hydroxyethyl starch is a suitable colloid plasma substitute to be used as priming solution in an extracorporeal circuit as well as peri- and postoperative infusion fluid, reasonably well maintaining hemostasis.

Shear-induced pathway of platelet function in cardiac surgery.

The contribution of platelet dysfunction to the impaired hemostasis after cardiac surgery remains to be established, because there is no sensitive method to assess platelet function. Measurement of the shear-induced pathway of platelet function, an important mechanism in inducing hemostasis, became possible by a novel shear-inducing technique, the in-vitro bleeding test (Thrombostat 4000). By using this test, the changes in platelet function during cardiopulmonary bypass and their contribution to hemostasis were investigated in patients undergoing cardiac surgery. Platelet function is quickly impaired shortly after the start of cardiopulmonary bypass, and partly recovered at the end of cardiopulmonary bypass. The function of aspirin-treated platelets is more severely affected than of nonaspirin platelets during cardiopulmonary bypass. Furthermore, the degree of platelet dysfunction at the end of the operation, but neither the platelet number nor the activated clotting time, was significantly correlated with blood loss from the chest drain after cardiac surgery. These results indicate the significant and variable effects of cardiopulmonary bypass on the shear-induced pathway of platelet function. Moreover, the impairment of this function of platelets appears to be a major cause of excessive bleeding in patients after cardiac surgery. Therefore, the routine use of the shear-inducing test seems helpful to make a proper diagnosis and design the therapy for bleeders after cardiac surgery.

Platelet function analysis after in vitro treatment with hemostasis-affecting components.

An overall platelet function test in whole blood, which simulates conditions under arterial pressure, is useful in measuring the effect of polymer materials on blood hemostatic function. We performed biocompatibility tests with materials or plasma substitutes by interaction of blood from healthy volunteers and then subjected these blood samples to platelet function analysis (Thrombostat). We tested also the capacity of locally applied hemostatic agents for bleeding control by direct application of these agents onto the Thrombostat measuring cell. The biocompatibility tests with materials exposed to blood appeared very discriminating between compatible and noncompatible materials. The hemostatic capacity of blood exposed to noncompatible materials (assessed by binding of active thrombin) reduced markedly after one hour incubation of the material. The plasma substitutes did not affect hemostasis significantly. However, a blood dilution of 40%, as in cardiopulmonary bypass, increased the time required for closure of the measuring cell by a platelet plug exponentially. Local hemostatic agents could be selected according to their capacity to enhance platelet plug formation. In addition, ADP mixed with the hemostatic agent was most effective in improving capacity. We conclude that platelet function analysis contributes importantly to screening of materials and plasma substitutes with regard to their interaction with primary hemostasis.

Blood compatibility of two different types of membrane oxygenator during cardiopulmonary bypass in infants.

The contact of blood with the artificial extracorporeal circuit causes a systemic inflammatory response due to blood activation. In this study, we compared two different paediatric membrane oxygenators used for extracorporeal circulation: a hollow fibre membrane oxygenator (Dideco Masterflo D-701, n = 10), and a flat sheet silicone membrane oxygenator (Avecor Kolobow 800-2A, n = 10). Blood compatibility was indicated by measuring complement activation as well as leukocyte and platelet activation. In patients perfused with a flat sheet membrane oxygenator, concentrations of complement split products C3a were significantly increased 30 minutes after the start of bypass (p < 0.01), whereas only a mild increase of C3a was found in patients perfused with a hollow fibre membrane oxygenator. Leukocyte and platelet counts dropped uniformly in both groups after the start of bypass mainly due to hemodilution. Activation of leukocytes and platelets identified by both plasma beta-glucuronidase and beta-thromboglobulin was similar in both groups. Infants perfused with a flat sheet membrane oxygenator received significantly more donor blood than those perfused with a hollow fibre oxygenator (p < 0.05). These results indicate that when used during paediatric cardiopulmonary bypass, a flat sheet membrane oxygenator has a higher complement activity than a hollow fibre membrane oxygenator, which is probably due to the relatively larger blood-surface contacting area of the oxygenator.

Monitoring of anticoagulation in aprotinin-treated patients during heart operation.

Since aprotinin has become extensively used during cardiopulmonary bypass the maintenance of safe anticoagulation is a concern. Aprotinin affects anticoagulation measurement by the activated clotting time. Therefore, a reliable new measurement is needed to monitor anticoagulation during cardiopulmonary bypass. In the present study, we tested the efficacy of two alternative measurements in which whole blood clotting was stimulated by high-dose thromboplastin or by high-dose thrombin. During cardiopulmonary bypass under standardized heparinization, the activated clotting time was twofold longer in the aprotinin group than in control group (p < 0.05), whereas high-dose thromboplastin and high-dose thrombin groups were not significantly affected by aprotinin. In laboratory tests using blood from healthy volunteers, all methods showed linear correlation with heparin concentration in the absence of aprotinin (p < 0.05). However, the activated clotting time measurement was prolonged more by heparin when aprotinin was present (p < 0.05), whereas high-dose thromboplastin and high-dose thrombin measurements were not. Moreover, these measurements were faster and more dependable than the activated clotting time. Therefore, high-dose thromboplastin time and high-dose thrombin time seem to be reliable for monitoring anticoagulation when aprotinin is used during cardiopulmonary bypass.

Clinical comparison between four modern membrane oxygenators: Bentley CM 40/50, COBE CML, Sci Med 3500-2A and Travenol LPM 50.

The devices with flat polypropylene membranes can be primed simpler and faster, than devices with the capillary membranes or with silicone rubber membranes. These two devices also offer more protection against venous air admixture and leaking of bubbles across the membrane. From hematologic standpoint there was no clear advantage of one particular device over another.

Hematological effects of a new hollow fiber membrane oxygenator: a clinical study.

UNLABELLED: The hemocompatibility of a new hollow fiber membrane oxygenator, BOS- CM40 , was evaluated during and after cardiopulmonary bypass for coronary artery bypass graft operations in 10 patients. Blood cells were well preserved by this oxygenator. In particular, platelet numbers at the end of bypass were significantly higher than at the start of bypass and platelet function remained completely intact during bypass. After protamine hydrochloride administration, platelet function decreased slightly but platelet numbers remained unaltered. After release of the aortic cross-clamp the beta-thromboglobulin concentration sharply increased, which shows the damaging effect of cardiotomy suction. Nevertheless, platelet numbers and function did not decrease significantly during this period. Apparently, platelet number and function can remain unaffected by this damaging procedure, provided they are normal before the start of suction. The average postoperative blood loss was 551 ml, which appears to be less than the blood loss in a previous study in which a membrane oxygenator of the envelope type was used. (J. Thorac . Cardiovasc . Surg . 83 (1983) 108-116). IN CONCLUSION: The BOS- CM40 hollow fiber membrane oxygenator proved to be highly hemocompatible .