There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore, an understanding of factors which impact on platelet performance is important. The present study was undertaken 1. to characterize during evolving myocardial infarction (MI) platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and 2. to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving MI were studied. 22 patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 minutes. In 15 of these patients, who had an anterior MI, transcardiac platelet function and response to PGI2 were studied. The results are as follows: Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, are elevated three and ten fold. 6-keto-prostaglandin F1 alpha, the stable end product of PGI2, is less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets, circulating during evolving MI ("ischemic platelets") are hyperaggregable in response to adenosine diphosphate and relatively resistent to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic adenosine monophosphate and the cAMP response to PGI2 are diminished. The platelet hyper-reactivity is most intense early during infarct evolution and decreases with time. Transcardiac measurements indicate that thromboxane is produced across the ischemic/infarcting compartment in ten of 15 patients with anterior MI. The antiplatelet effect of PGI2 is greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving MI characterized by a pro-aggregatory environment, heightened platelet re-activity, both in the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequence of the data are that the infarct patient in the acute phase may benefit from platelet function suppression and requires significantly greater doses of prostacyclin than normal subjects. The data also suggest future directions for therapeutic manipulation of platelet hyper-reactivity in the setting of acute myocardial ischemia.

To evaluate the relationship between the physiological cardiac hypertrophy associated with physical training and the increases in vascular capacitance associated with this stimuli, male and female rats trained by a swimming program were studied. Both sexes were used so that the coronary vascular response to exercise could be studied in the presence (females) and absence (males) of cardiac hypertrophy. Coronary vascular reserve was assessed in isolated retrograde buffer-perfused hearts under conditions of minimal coronary resistance (15 microM adenosine or anoxia). Both groups demonstrated an increase in coronary vascular reserve after 8 wk of exercise swim training, male animals increasing flow (per g of myocardium) by 15% and females by 18%. When the time course of this response was compared in female animals with the time course of the development of myocardial hypertrophy, it was evident that the vascular changes occurred early, greater than 80% of the response was seen within the first 10 days of exercise, compared with an approximately 35% increase in cardiac mass. These data suggest that the vascular response to exercise swim training is independent of the hypertrophic response and further that the increase in coronary vascularity is an early event in the cardiac adaptation to a physiological load.

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)