Gelatin use impairs platelet adhesion during cardiac surgery.

Artificial colloids based on gelatin are used as plasma expander to replace donor blood products. In laboratory experiments, gelatin reduced both the velocity and extend of platelet agglutination by ristocetin, and only the agglutination velocity by polybrene (p < 0.05). Furthermore, gelatin delayed the in-vitro platelet plug formation under shear-stress in the absence of ADP (p < 0.05), whereas gelatin induced no delay in the presence of ADP. Thus, after induction of vWF release from platelets by polybrene or ADP, platelet function was normal. These results indicate that gelatin affects in particular the functionality of plasma-vWF and partly inhibits platelet adhesion. These negative effects of gelatin on hemostasis were demonstrated in two clinical studies during cardiac surgery. In a randomized study of sixty patients undergoing cardiac surgery, gelatin as prime in the heart-lung machine appeared to result in diminished efficacy of aprotinin on hemostasis, whereas it did not affect hemostasis in non-aprotinin patients. An additional retrospective clinical study showed that only high dose of gelatin affected hemostasis. This suggests a limited role of plasma-vWF and a strong back-up mechanism of platelet-vWF in achieving hemostasis.

Hemostatic function of aspirin-treated platelets vulnerable to cardiopulmonary bypass. Altered shear-induced pathway.

The impaired hemostasis of aspirin-treated patients is an annoying problem during and after cardiopulmonary bypass. The hemostatic function of platelets comprises two mechanisms: the shear-induced and the cyclooxygenase pathways. Because the latter is inhibited in aspirin-treated patients, the hemostatic function depends mainly on the former pathway. To investigate the effect of cardiopulmonary bypass on the shear-induced pathway, a double-blind study of preoperative aspirin treatment (325 mg) and placebo was conducted in 40 patients undergoing coronary artery bypass grafting. Postoperative blood loss was higher in the aspirin-treated patients than in the placebo-treated patients (p < 0.05). The shear-induced hemostasis was monitored by the in vitro bleeding test (Thrombostat), which mimics bleeding through an injured arteriole. The shear-induced pathway of aspirin-treated platelets was not affected before cardiopulmonary bypass, but it was impaired more during the operation (p < 0.01) and remained worse afterward (p < 0.05), compared with that of placebo-treated platelets. The inhibitory effects of aspirin on thromboxane production and on collagen-induced platelet aggregation remained throughout the operation. In aspirin-treated platelets, the aggregation capacity induced by adenosine diphosphate was inhibited before the operation (p < 0.05) and showed substantial recovery during the operation (p < 0.05). These results suggest that the shear-induced pathway of aspirin-treated platelets is more vulnerable to cardiopulmonary bypass than the pathway in normal platelets and causes severe impairment of hemostasis afterward.

Complex II inactivation is lethal in the nematode Caenorhabditis elegans.

RNA-mediated interference (RNAi) was employed to systematically inactivate the four subunits of complex II in the mitochondrial electron transport chain. Embryonic lethality was the predominant result of inactivating three subunits (ceSDHB, ceSDHC, and ceSDHD) when using the soaking method to inactivate RNA. The feeding method was employed to deliver dsRNA from the fourth subunit (ceSDHA) to wild-type, mev-1 (mutated in ceSDHC of complex II), and gas-1 animals (mutated in a complex I gene). Survival was reduced only in the mev-1 genetic background, and in an oxygen-dependent fashion. Collectively, these data provide further evidence that compromised complex II integrity can result in sensitivity to oxidative stress.

Aprotinin preserves hemostasis in aspirin-treated patients undergoing cardiopulmonary bypass.

Various clinical trials have shown that hemostasis is improved by the administration of aprotinin during cardiopulmonary bypass. However, this effect has not been proved for those patients treated preoperatively with aspirin. Therefore, a double-blind, placebo-controlled study was conducted to test the efficacy of low-dose aprotinin (2 x 10(6) KIU in the pump prime solution) in preserving hemostasis in 40 aspirin-treated (325 mg) patients undergoing coronary artery bypass grafting. Aprotinin brought about a decrease in the postoperative blood loss (p < 0.05). The in vitro bleeding test (Thrombostat) demonstrated that aprotinin preserved the platelet hemostatic function in aspirin-treated patients during cardiopulmonary bypass (p < 0.05). The inhibitory effects of aspirin on collagen-induced platelet aggregation and thromboxane production were not influenced by aprotinin treatment. The findings from the present study indicate that aprotinin preserves hemostasis in aspirin-treated patients during cardiopulmonary bypass, but aspirin's effect on platelets is maintained. Therefore, aprotinin seems to be a useful adjunct treatment in aspirin-treated patients undergoing coronary artery bypass grafting.

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.

Aprotinin effect on platelet function and clotting during cardiopulmonary bypass.

A variety of studies have been performed on the preservation of hemostasis by aprotinin during cardiopulmonary bypass (CPB). It appears that the mechanism of aprotinin to preserve hemostasis can be interpreted in different ways. Our previous studies suggested that preservation of platelet glycoprotein Ib (GpIb) antigen, and counteraction of heparin anticoagulation in the extrinsic clotting pathway might partly explain the preservative effect of aprotinin. A clinical study was therefore conducted to evaluate these effects during the use of low dose aprotinin. Improved agglutination by ristocetin (P < 0.05), and improved GpIb antigen expression (P < 0.05) during CPB showed better preserved platelet adhesive capacity in the aprotinin group than in the control group. Glycoprotein Ib antigen expression and the agglutination capacity with ristocetin during CPB were closely related (P < 0.05). Platelet GpIIb/IIIa antigen and adenosine diphosphate (ADP) aggregation were not significantly different between the aprotinin and control groups. Aprotinin had no effect on the extrinsic clotting pathway in the blood, since the thromboplastin clotting time was similar in both groups. These results indicate that the protection of platelet adhesive capacity during CPB is a main function of aprotinin, whereas no evidence was collected for enhanced extrinsic clotting by aprotinin during CPB.

[Lipomatous hypertrophy of the interatrial septum. Apropos of 3 cases and review of the literature]. / Hypertrophie lipomateuse du septum interauriculaire. A propos de 3 cas et revue de la littérature.

Lipomatous hypertrophy of the interatrial septum is characterised by an accumulation of fatty tissue in the interatrial septum. The authors report three cases, one presenting with sinus tachycardia and the other two being chance findings. Echocardiography associated with cardiac computerised tomography or magnetic resonance imaging usually confirms the diagnosis. In half the cases, supraventricular arrhythmias and suggestive P wave abnormalities are observed on the electrocardiogram. The diagnostic value of transoesophageal echocardiography is emphasised; it demonstrates the massive forms which may obstruct flow from the superior vena cava into the right atrium. The authors observe a discrepancy between the prevalence of this condition in autopsy series (about 1%) and the small number of cases described at echocardiography, suggesting that the diagnosis is probably missed.