Effect of prostacyclin infusion during low-flow ischaemia in the isolated perfused rat heart

Abstract

Although prostacyclin (PGI2) has been shown to exert a protective effect on ischaemic hearts its precise mode of action remains obscure. Possible explanations include protection of the high energy phosphate stores (ATP and CP), maintenance of homeostasis with respect to Ca2+, and an antiaggregatory effect. The following experiments were undertaken to investigate these possibilities, using isolated, spontaneously beating rat hearts perfused with Krebs-Henseleit solution. Ischaemia was induced at 37 degrees C for 30 min by reducing the flow rate from 10.0 to 0.1 ml/min, and was followed by reperfusion. PGI2 was given as a constant infusion (20 ng/ml). The hearts were frozen and assayed for ATP and CP, or digested in HNO3 and assayed for Ca2+. Peak developed tension was recorded throughout. The results show that PGI2 slowed the rate of decline of developed tension during low flow perfusion, and hastened the recovery of contractions on reperfusion. These effects could not be accounted for in terms of an improved supply of ATP or CP, or an altered tissue Ca2+. The protective effect of PGI2 on isolated, buffer-perfused hearts may be a reflection of a generalized, but undefined, mechanism of cell preservation which has also been observed in other systems.

Ischemia-reperfusion arrhythmias and lipids: Effect of human high- and low-density lipoproteins on reperfusion arrhythmias

“…PGI 2 formed in the blood vessel endothelium is thought to act as an antagonist against TXA 2. Administration of PGI 2 or PGI 2 analog has been reported to have improved the protection against reduced myocardial contractility [21]. In the present study, PGI~ increased significantly during ischemia when LDL was infused.…”

L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes

“…However, the role of PGI 2 in the protective mechanisms of L-carnitine in the heart has not been determined. PGI 2 has been reported to alleviate myocardial ischemia-reperfusion injury [23,24]. Due to the short half-life of PGI 2 ; therefore, the more stable PGI 2 analogs were developed.…”

Direct Myocardial Effects of the Thromboxane A₂/Prostaglandin H₂ Agonists U-46619 and SQ 26,655 under Ischemic and Nonischemic Conditions

“…The data from this part of the study indicate that TXAt mimetics may be reducing LDH release because of their ability to induce production of other prostanoids with protective actions. One possibility is prostacyclin which has been shown to have beneficial effects during myo cardial ischemia [27], We showed that pros tacyclin production was increased by U-46619 treatment during ischemia in the buff er-perfused rat heart. As previously pub lished [ 18], we found that ischemia itself also increased prostacyclin production, but U-46619 further increased its production.…”