LOSS OF PLATELET ALPHA-2-ADRENERGIC RECEPTORS DURING SIMULATED EXTRACORPOREAL-CIRCULATION - PREVENTION WITH PROSTAGLANDIN-E1

  • 1 January 1985
    • journal article
    • research article
    • Vol. 105  (5) , 601-607
Abstract
During in vitro recirculation in an extracorporeal circuit containing a membrane oxygenator and primed with fresh heparinized human blood, thrombocytopenia, impaired platelet aggregation, and depletion of granular contents, all of which were prevented with prostaglandin E1(PGE1) were observed. The number and affinity of platelet .alpha.2-adrenergic receptors was studied by measuring the binding of 3H-yohimbine. Before recirculation, 235 .+-. 28 .alpha.2-adrenergic receptors/platelet, a Kd of 3.37 .+-. 0.78 nmol/l, complete aggregation with 1.04 .mu.mol/l epinephrine, and a platelet count of 281,000 .+-. 33,000 .mu.1-1 were found. After 2 min of recirculation, 9.44 .mu.mol/l epinephrine was required to produce complete aggregation, and 9.44 .mu.mol/l epinephrine was required to produce complete aggregation, and the platelet count was 104,000 .+-. 22,000 .mu.1-1 (44% of control). The number of binding sites significantly decreased to 139 .+-. 16/platelet, but the affinity did not change (Kd = 3.78 .+-. 0.44 nmol/l). After 2 h of recirculation, the platelet count had increased to 123,000 .+-. 21,000 .mu.1-1. Epinephrine did not induce platelet aggregation even at 100 .mu.mol/l. .alpha.2-Adrenergic binding sites were not detectable, and affinity for yohimbine could not be calculated. Two minutes after PGE1 0.3 .mu.mol/l was added to the circuit, platelet numbers, response to epinephrine, .alpha.2-adrenergic binding sites/platelet, and affinity for yohmibine were not significantly different from control values. At 2 h, the number of .alpha.2-adrenergic sites was not significantly changed from control, but the affinity of yohimbine for platelets was significantly decreased 2.5-fold. Changes in platelet sensitivity to epinephrine during in vitro extracorporeal recirculation parallel the decrease in .alpha.2-adrenergic binding sites without change in affinity for the .alpha.2-adrenergic antagonist yohimbine. PGE1 largely prevents tha loss of platelet .alpha.2-adrenergic receptors, probably by decreasing the reactivity of platelets with the synthetic surfaces.