Pump-induced platelet aggregation with subsequent hypotension: Its mechanism and prevention with clopidogrel

ObjectivesUse of extracorporeal circuits in cardiopulmonary bypass and hemodialysis often causes bleeding problems and hypotension. As shown previously, this might be caused by activation of blood platelets due to pumping. The present study investigates the mechanism of pump-induced platelet aggregation and its possible prevention.Methods and ResultsContinuous measurement of platelet aggregation in an extracorporeal shunt from a carotid to a femoral artery in rats showed that aggregation during the first 10 minutes of pumping was not reduced by coating the tube with albumin or heparin nor by using dalteparin instead of unfractionated heparin as anticoagulant. Also, pump characteristics seemed unimportant because aggregation could already be elicited by single tube compression with one pump roller. It was calculated that during compression wall shear stress in the tube rises far beyond the values known to induce platelet aggregation, occurring also in clinically used roller pumps. A crucial role for adenosine diphosphate was demonstrated by blockade of platelet adenosine diphosphate-P2Y12 receptors with the clinically used drug clopidogrel (50 mg/kg intravenously, n = 8). This prevented platelet aggregation and the fall of systemic blood pressure (to 71% ± 12% in controls, n = 6) during 2 hours of continuous pumping.ConclusionWe conclude that pump-induced platelet aggregation is not caused by factors released from the tube or its coating but is initiated by short bouts of high shear stress, and its continuation is critically dependent on adenosine diphosphate. The latter might have clinical relevance for patients connected to extracorporeal systems

Pump-induced platelet aggregation with subsequent hypotension: Its mechanism and prevention with clopidogrel

ObjectivesUse of extracorporeal circuits in cardiopulmonary bypass and hemodialysis often causes bleeding problems and hypotension. As shown previously, this might be caused by activation of blood platelets due to pumping. The present study investigates the mechanism of pump-induced platelet aggregation and its possible prevention.Methods and ResultsContinuous measurement of platelet aggregation in an extracorporeal shunt from a carotid to a femoral artery in rats showed that aggregation during the first 10 minutes of pumping was not reduced by coating the tube with albumin or heparin nor by using dalteparin instead of unfractionated heparin as anticoagulant. Also, pump characteristics seemed unimportant because aggregation could already be elicited by single tube compression with one pump roller. It was calculated that during compression wall shear stress in the tube rises far beyond the values known to induce platelet aggregation, occurring also in clinically used roller pumps. A crucial role for adenosine diphosphate was demonstrated by blockade of platelet adenosine diphosphate-P2Y12 receptors with the clinically used drug clopidogrel (50 mg/kg intravenously, n = 8). This prevented platelet aggregation and the fall of systemic blood pressure (to 71% ± 12% in controls, n = 6) during 2 hours of continuous pumping.ConclusionWe conclude that pump-induced platelet aggregation is not caused by factors released from the tube or its coating but is initiated by short bouts of high shear stress, and its continuation is critically dependent on adenosine diphosphate. The latter might have clinical relevance for patients connected to extracorporeal systems

Alterations in Nitric Oxide Activity and Sensitivity in Early Streptozotocin-Induced Diabetes Depend on Arteriolar Size

Changes in NO activity may play an important role in the early increase in microvascular flow that has been implicated in the pathogenesis of diabetic microangiopathy. We assessed, in the in situ spinotrapezius muscle preparation of 6 weeks' streptozotocin-diabetic rats (n = 6) and of agematched controls (n = 8), basal inside diameters of A2–A4 arterioles and the reactivity to topically applied acetylcholine and nitroprusside, before and after NG-nitro-L-arginine. In diabetic rats, cholinergic vasodilatation in A2–A4 arterioles was intact. Basal diameter in A3 and A4 arterioles was significantly higher in streptozotocin-diabetic rats. The increased basal diameter in A3 arterioles was partially due to an increased contribution of NO to basal diameter. The response to nitroprusside was impaired in streptozotocin-diabetic rats in A2, but not in A3 and A4 arterioles. Thus, this study shows that NO activity and sensitivity are altered after 6 weeks of streptozotocin-induced diabetes. These streptozotocin-induced changes are anatomically specific and, for arterioles, depend on their position within the vascular tree

Pump-induced platelet aggregation in albumin-coated extracorporeal systems

AbstractObjective: Coating of extracorporeal systems with heparin does not prevent platelet activation and subsequent bleeding disorders. We investigated whether this could be due to elevated shear stress caused by a roller pump. Methods: Human or rat blood was made to flow through an uncoated or an albumin-coated medical polyvinyl chloride tube with or without a roller pump. Aggregation of platelets in the tubing was recorded continuously with a photometric device. Results: Although in vitro gravitational flow in uncoated tubes caused immediate platelet aggregation and platelet loss, this remained absent in coated tubes. When the pump was started in experiments with a coated tube strong platelet aggregation was observed and platelet count fell within 5 minutes to 78% ± 2% and 71% ± 3% of control values in human and rat blood, respectively. In vivo, no aggregation was observed during spontaneous flow in rats with an albumin-coated tube running from the carotid artery to the femoral artery, but aggregation started as soon as the blood was pumped. Pump-induced platelet aggregation, both in vitro and in vivo, could be prevented with aurintricarboxylic acid, which specifically inhibits shear-induced platelet aggregation as has recently been shown. Pump perfusion of blood in an uncoated tube did not elicit platelet aggregation. Conclusions: Pump perfusion of blood in coated systems elicits shear-induced platelet aggregation, which may be prevented by administration of substances that block the binding of von Willebrand factor to glycoprotein Ib receptors on the platelets. The effects of pumping on platelets are masked in uncoated circuits because of the dominant influence of blood-material contact. (J Thorac Cardiovasc Surg 1999;118:946-52