Loss of platelet alpha 2-adrenergic receptors during simulated extracorporeal circulation: prevention with prostaglandin E1.
Cardiopulmonary bypass prolongs bleeding time and increases postoperative blood loss. During in vitro recirculation in an extracorporeal circuit containing a membrane oxygenator and primed with fresh heparinized human blood, we previously observed thrombocytopenia, impaired platelet aggregation, and depletion of granular contents, all of which were prevented with prostaglandin E1 (PGE1). To investigate these changes further, we studied the number and affinity of platelet alpha 2-adrenergic receptors by measuring the binding of 3H-yohimbine. Before recirculation, we found 235 +/- 28 alpha 2-adrenergic receptors per platelet, a Kd of 3.37 +/- 0.78 nmol/L, complete aggregation with 1.04 mumol/L epinephrine, and a platelet count of 281,000 +/- 33,000 microliters-1. After 2 minutes of recirculation, 9.44 mumol/L epinephrine was required to produce complete aggregation, and the platelet count was 104,000 +/- 22,000 microliters-1 (44% of control). The number of binding sites significantly decreased to 139 +/- 16 per platelet, but the affinity did not change (Kd = 3.78 +/- 0.44 nmol/L). After 2 hours of recirculation, the platelet count had increased to 123,000 +/- 21,000 microliters-1. However, epinephrine did not induce platelet aggregation even at 100 mumol/L. Moreover, alpha 2-adrenergic binding sites were not detectable, and affinity for yohimbine could not be calculated. Two minutes after PGE1 0.3 mumol/L was added to the circuit, platelet numbers, response to epinephrine, alpha 2-adrenergic binding sites per platelet, and affinity for yohimbine were not significantly different from control values. At 2 hours, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000527:Alprostadil; D001792:Blood Platelets / Q000032:analysis / Q000648:ultrastructure*; D004837:Epinephrine / Q000502:physiology; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D011458:Prostaglandins E / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000097:blood*; D013997:Time Factors; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism
D011458:Prostaglandins E; D011941:Receptors, Adrenergic; D014316:Tritium; D015016:Yohimbine; D000527:Alprostadil; D004837:Epinephrine