Significance of platelet function and thromboxane B2 levels across the human myocardial vascular bed.

Abstract

ABSTRACTThere is an intense interest in the role of platelets in the pathogenesis of myocardial ischemia. To determine platelet function in coronary circulation and the influence of various platelet‐active drugs, we have studied large number of patients with coronary disease (CD) defined as >50 % luminal narrowing and subjects with normal coronary arteries (NCA). Blood samples were collected from aorta (Ao) and coronary sinus (CS) at rest, during and following atrial‐pacing induced tachycardia characterized by ECG changes and symptoms. Platelet aggregation (PAg) using epinephrine (E) and adenosine diphosphate (ADP) as stimulating agents and platelet counts were performed. In CD patients CS blood had lower (Pd<0.01) PAg (E‐59 ± 8, ADP‐49 ± 7 %) than Ao blood (E‐74 ± 6, ADP‐68 ± 7 %). Platelet counts in CS blood (173,000 ± 16,000/mm3) were lower (P<0.01) than in Ao blood (233,000 + 30,000/mm3). In NCA patients, the CS and Ao platelet counts and PAg were not significantly different. During tachycardia stress PAg and counts were unaltered in NCA patients. In contrast in CD patients PAg increased significantly (P<0.05) in CS but not in Ao blood during stress and returned to baseline following tachycardia implying platelet activation during stress‐induced myocardial ischemia. Oral aspirin 650 mg abolished the differences in Ao and CS blood PAg (CS‐E 51 ± 8, ADP 54 ± 7%; Ao‐E 45 ± 8, ADP 55 ± 8 %), and in counts (CS‐221,000 ± 8,000/mm3; Ao‐230,000 ± 71,000/mm3) in CD patients. Aspirin also significantly decreased tachycardia‐related increase in PAg in CS blood. Administration of intravenous dipyridamole 25 mg in 8 other CD patients, resulted in increase in platelet counts in CS from 255,000 ± 29,000 to 286 ± 34,000/mm3 and in PAg from 30 ± 8 to 52 ± 9 %, while Ao blood counts and PAg were unchanged, so that the differences in Ao and CS platelet counts and aggregation were abolished. In other studies, we compared CD patients treated with and without propranolol. Propranolol‐treated patients had lower PAg in Ao as well as CS blood compared to non‐treated patients, but the gradients in PAg and counts between Ao and CS blood was still present. However, tachycardia‐related increase in CS PAg was markedly less in CS blood in propranolol‐treated patients compared to non‐treated patients.These data show that 1) gradient in platelet counts from Ao to CS exists related probably to platelet aggregate formation in atherosclerotic vessels, 2) activation of platelets leads to low PAg activity in CS blood, 3) tachycardia stress is associated with platelet activation at the level of myocardial vascular bed, 4) aspirin and dipyridamole modify these gradients, 5) aspirin blunts tachycardia‐related increase in CS PAg, 6) propranolol has potent PAg inhibitory effects and modifies platelet response to tachycardia stress.