Prostacyclin: A Potentially Valuable Agent for Preserving Myocardial Tissue in Acute Myocardial Ischemia

Am, Lefer; Ogletree, Martin L.; Smith, J B; Silver, Melvin J.; Nicolaou, K. C.; Barnette, W. E.; Gasic, G. P.

doi:10.1126/science.345441

Cited by 233 publications

(57 citation statements)

References 28 publications

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“…These data, along with the observation that significant numbers of platelet emboli are not present in small pulmonary vessels as demonstrated by electron microscopy, suggest that PGI2 has the ability to reverse the aggregation process in vivo in the pulmonary vascular bed. The present results are in agreement with in vitro studies with the aggregometer in whch PGI2 was a potent inhibitor of platelet aggregation Gryglewski et al, 1976;Lefer et aL, 1978). It has been reported recently that isolated perfused lungs of rats and guinea pigs and the lungs of anesthetized cats spontaneously release a "PGI2-like" substance (Gryglewski et aL, 1978).…”

Section: Discussionsupporting

confidence: 81%

“…PGI 2 relaxes strips of mesenteric and celiac arteries but not strips from aorta and vena cava . Prostacyclin decreases systemic arterial pressure in all species in which it has been studied, and a PGI 2 analog has been shown to have marked vasodilator activity in the feline pulmonary lobar and mesenteric vascular beds Paustian et al, 1977;Armstrong et al, 1978;Fitzpatrick et al, 1978;Lefer et al, 1978). Although PGI 2 is formed in blood vessels, "PGl2-like" substances are released from the lung, and the metabolite, 6-keto-PGFi a , is released from the lung after immunological challenge, the direct effects of PGI 2 on the pulmonary vascular bed are uncertain (Dawson et al, 1976;Gryglewski et aL, 1976;Gryglewski et al, 1978).…”

mentioning

confidence: 99%

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Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Hyman¹,

Kadowitz²

1979

Circulation Research

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IN the lung, arachidonic acid is transformed into the cyclic endoperoxide intermediates, PGG2 and PGH 2 , by a microsomal cyclooxygenase (Nugteren and Hazelhof, 1973;Hamberg and Samuelsson, 1974). The endoperoxide intermediates then are converted by specific terminal enzymes into prostaglandins (PG), thromboxane A2, and a newly discovered bicyclic prostaglandin, prostacyclin, or PGI 2 (Nugteren and Hazelhof, 1973;Hamberg and Samuelsson, 1974;Gryglewski et al., 1976). PGI 2 is the major metabolic product formed from arachidonic acid and endoperoxide intermediates in vascular tissue and, since PGI 2 is a potent inhibitor of platelet aggregation, it has been postulated that it may serve to protect vessel endothelium from the adverse effects of intravascular platelet aggregationFrom the

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Hyman¹,

Kadowitz²

1979

Circulation Research

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“…Prostacyclin has been shown to have a cardioprotective effect during acute myocardial ischaemia and reperfusion (Lefer et al, 1978;Ogletree et al, 1979;Araki et al, 1980;Jugdutt et al, 1981;Schror et al, 1981;Melin et al, 1983;Berti et al, 1990), although the exact mechanism for this cardioprotective effect is still unclear. The present study suggests that, like prostacyclin, beraprost may have cardioprotective effects with respect to both action potential and contractile force in guinea-pig ventricular muscles during hypoxia-reoxygenation.…”

Section: Discussionmentioning

confidence: 99%

“…With respect to inotropic effects of prostacyclin, contradictory results have been reported. Lefer et al (1978) showed that prostacyclin does not produce any direct inotropic effect on electrically driven papillary muscles of the cat but Fassina et al (1983) described positive inotropic effects of prostacyclin, on guinea-pig isolated atria. This was also confirmed by the fact that the shortening of APD induced by 50pmoll1' pinacidil was not antagonized by beraprost.…”

Section: Discussionmentioning

confidence: 99%

“…Beraprost (sodium (( + )-IR*, 2R*, 3aS*, 8bS*)-2,3,3a,8b-tetrahydro-2-hydroxyl-1 -[(E)-(3S)-3-hydroxy-4-methyl -1-octen-6-ynyl]-1H-cyclopenta [b] benzofuran-5-butyrate) is a chemically stable prostacyclin analogue which can be administered orally and has been demonstrated to possess a similar pharmacological profile to prostacyclin, i.e., potent antiplatelet aggregation effect in vitro and ex vivo in various animal species (Umetsu et al, 1987;Nishio et al, 1988), antithrombotic effect on arterioles in the hamster cheek pouch (Sim et al, 1985) and vasodilator effects in the dog (Akiba et al, 1986). Prostacyclin has been reported to possess a cardioprotective effect during acute myocardial ischaemia and reperfusion in in vitro and in vivo animal models (Lefer et al, 1978;Ogletree et al, 1979;Jugdult et al, 1981;Melin et al, 1983;Berti et al, 1990). A number of preliminary clinical studies with prostacyclin have demonstrated haemodynamic benefits in heart failure (Yui et al, 1982;1984;Auinger et al, 1989).…”

Section: Introduction Methodsmentioning

confidence: 99%

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Effects of beraprost on the transmembrane potentials of guinea‐pig ventricular muscles during normoxia and hypoxia‐reoxygenation

Ueno

Shigenobu

Nishio

1993

British J Pharmacology

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1 The present study was performed to determine whether beraprost, a new stable analogue of prostacyclin, may exert beneficial effects on the transmembrane action potentials during normoxia and hypoxia-reoxygenation in isolated right ventricular muscles of the guinea-pig.2 Under normal oxygenation, beraprost (0.01-100 imol'1) had no effects on the electrophysiological parameters. 3 Hypoxic conditions induced a decrease in action potential duration (APD) without affecting other action potential parameters. Beraprost inhibited this hypoxia-induced decrease in APD. However, beraprost had no effect on the decrease in contractile force induced by hypoxia, whereas it significantly improved the recovery of contractile force after reoxygenation. 4 Pinacidil-induced shortening of APD was not antagonized by beraprost. 5 Hypoxia significantly decreased the myocardial adenosine triphosphate (ATP) level, which was also prevented by beraprost. 6 These results suggested that beraprost may inhibit the hypoxia-induced shortening of APD by some mechanisms which contribute to the maintenance of muscle ATP level.

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Status of Antiplatelet Drugs in Coronary Heart Disease

Mehta¹

1979

JAMA

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A RECENT report suggesting prevention of cardiac death after myocardial infarction in patients given sulfinpy-razone1 has renewed interest in antiplatelet drugs within the medical profession. During the last few years, it has become clear that blood platelets are involved in arterial and venous obstruction and in the origin of smooth-muscle hypertrophy and possibly atherogenesis. If altered platelet function is related to the pathogenesis of coronary disease and subsequent cardiovascular mortality and morbidity, the use of antiplatelet drugs in patients with coronary heart disease would be rationalized. Our purpose is to review information on the role of platelets in coronary artery disease and to show how antiplatelet drugs might affect platelet function and thereby influence coronary vascular disease. Role of Platelet Function in Coronary Artery DiseaseIn animal models of myocardial ischemia induced by experimental coronary narrowing, platelet aggregates appear within a short time in coronary vessels.2,3 These aggregates may occlude the microcirculation, reduce blood flow, and result in myocardial injury. The observation of platelet aggregates in the coronary arteries of patients dying suddenly" and the absence of total obstruction of the coronary lumen of certain patients with myocardial infarction also suggest involvement of platelets in coronary disease. Furthermore, it has been shown that patients with myocardial infarction and other is¬ chémie lesions have a notable in¬ crease in circulating platelet aggre¬ gates.Studies with selected patients with coronary artery disease have shown that platelet aggregation is consider¬ ably lower in the coronary venous blood compared with the aortic blood.5 In addition, appreciably lower platelet counts are present in the coronary venous blood, suggesting either sequestration of more active platelets or formation of platelet aggregates in the atherosclerotic ves¬ sels. No such differences in platelet function or number are noticed across the coronary vascular bed in subjects with normal coronary arteries. Ad¬ ministration of aspirin results in prompt elimination of these differ¬ ences in platelet counts and aggrega-tion across the diseased coronary vascular bed.Several clinical studies have shown that patients with coronary heart disease have increased platelet aggre¬ gation and adhesion and decreased platelet survival.6 Similar platelet function abnormalities have also been described in diabetes mellitus, hyper¬ tension, and hyperlipidemias, condi¬ tions that are considered risk factors in the origin and propagation of coro¬ nary artery disease.Work on the interrelationship of prostaglandins and platelet function has further helped in understanding involvement of platelets in thrombo¬ sis and coronary disease.7 Some human prostaglandins stimulate platelet aggregation, whereas others inhibit it. As platelets come in contact with collagen (ie, in a dam¬ aged vessel wall), conversion of cyclic endoperoxides (prostaglandins G2 and H2) to thromboxane A2 occurs. Thromboxane A...

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Prostacyclin: A Potentially Valuable Agent for Preserving Myocardial Tissue in Acute Myocardial Ischemia

Cited by 233 publications

References 28 publications

Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

Effects of beraprost on the transmembrane potentials of guinea‐pig ventricular muscles during normoxia and hypoxia‐reoxygenation

Status of Antiplatelet Drugs in Coronary Heart Disease

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