IMPAIRED PROSTAGLANDIN-E1/I2 RECEPTOR ACTIVITY OF HUMAN BLOOD-PLATELETS IN ACUTE ISCHEMIC-HEART-DISEASE

The platelets from 74 patients with acute myocardial infarction or with unstable angina showed decreased prostaglandin E1/I2 receptor activity when compared with that of 56 normal volunteers by using [3H]prostaglandin E1 as a probe. In normals, Scatchard analyses showed the presence of one high-affinity-low-capacity (K(d1) = 9.0 ± 1.2 nM [mean ±SD]; n1 = 120 ± 30 sites/cell) and one low-affinity-high-capacity (K(d2) = 1.1 ± 0.5 μM; n2 = 1,460 ± 250 sites/cell) prostaglandin E1/I2 receptor population in platelets. In contrast (p<0.01), platelets from patients showed decreased ligand binding (n1 = 40 ± 20 sites/cell; n2 = 800 ± 210 sites/cell) with little change in the affinity of the receptor (K(d1) = 7.50 ± 1.6 nM; K(d2) = 0.68 ± 0.24 μM). On the other hand, the platelets from the patients with dilated cardiomyopathy (n = 7) who were hospitalized for acute chest pain but had normal coronary arteries did not show any impairment of the receptor activity. The plasma prostacyclin level of the patients with acute ischemic heart disease was similar to that of normal volunteers; this finding indicated that the defective receptor function was not related to the prostaglandin receptors occupancy in vivo. The impaired receptor activity was temporary in nature. The follow-up studies showed that the prostaglandin receptor activity of the patients' platelets improved to 'normal' levels within 2-8 weeks. The decreased prostaglandin E1 binding to its receptors in the platelets from acute ischemic heart disease also resulted in the similar reduction of the formation of cyclic AMP by 1.0 μM prostaglandin E1 (7.5 ± 2.0 pmol/108 cells [mean ± SD]) when compared with the control platelets (16.35 ± 0.91 pmol/108 cells). These results show that the defective prostaglandin E1/I2 receptors of platelets are probably pathophysiologically more important than the altered synthesis of prostacyclin in acute ischemic heart disease.