Physiological concentrations of epinephrine potentiate thromboxane A2 release from platelets in the isolated rat heart.

Abstract

The isolated rat heart perfused with washed platelets was used as a model to examine platelet-vessel wall interactions. Release of prostacyclin and thromboxane A2 was measured, using a cascade of smooth muscle bioassay tissues or radioimmunoassays of the stable hydration products. In hearts perfused with rabbit or human platelets, injection of sodium arachidonate caused release of both prostacyclin and thromboxane A2. In hearts perfused with aspirin-pretreated platelets, arachidonate released only prostacyclin indicating that thromboxane A2 originates largely in the platelets. Infusion of epinephrine (0.6-6 nmol/liter) through the heart potentiated arachidonate-induced release of thromboxane A2. Similar potentiation of thromboxane A2 release was observed in rat hearts perfused with either rabbit or human platelets, and in rabbit hearts perfused with rabbit platelets. In contrast, when rabbit platelets were infused through an incubation coil of tubing in place of the heart, epinephrine did not alter thromboxane A2 release. There was no significant loss of rabbit platelets on perfusion through rat hearts, and no aggregates were observed in the effluent either before or immediately after arachidonate injections, even in the presence of epinephrine. Thus, potentiation of thromboxane A2 production could not be explained by aggregation. However, it is clear from these studies that physiological concentrations of epinephrine can potentiate thromboxane A2 release from platelets when they are stimulated by arachidonic acid within the heart. This could result from a redirection of arachidonate metabolism to a local potentiating factor in the vessel wall. Potentiation of thromboxane A2 release might contribute to myocardial ischemia associated with platelet activation.

Contribution of platelets and platelet-activating factor (PAF) to the arrhythmogenic, haemodynamic and necrotic effects of acute myocardial ischaemia

“…Following antiplatelet serum there was a prompt fall in platelet count from 625 +31 xlO 9 1" 1 to 80± 0-6 xlO'T 1 at 5 min (99% reduction, P< 0-0001), and thereafter the platelet count remained markedly depressed for more than 100 min (Fig. 1).…”

“…Catecholamines are known to cause platelet activation' 9 ' and, in high concentrations, to cause myocardial necrosis. Kammermeier and Ober" 0 ' observed that this catecholamine effect appears to be dependent on the presence of circulating platelets.…”

Role of catecholamines in platelet function: pathophysiological and clinical significance

“…In the isolated rat heart perfused with washed platelets following the Langerdorff 's technique, adrenaline infusion at concentrations within the physiological range potentiates the arachidonate-induced release of TXA 2 without inducing platelet aggregation [277]. Adrenaline infusion at rates determining blood levels achievable in physiological conditions of sympathoadrenal activation (over 4 nmol L ÿ 1 ) influences both the number of circulating platelets and the platelet function [136,[278][279][280][281].…”

Catecholamine release and potentiation of thromboxane A2 production by nicotine in the greyhound

“…Recently in our laboratory it has been found that infusion of adrenaline and other catecholamines in rat isolated hearts, greatly potentiates the release of thromboxane A2 from platelets perfused through the heart (Purchase et al, 1985). We set out to study whether nicotine would also produce this effect via endogenous catecholamine release in vivo.…”