Prostacyclin and iloprost: Equal efficiency in preserving high energy phosphates in the dog heart following coronary artery ligation

Abstract

The influence of PGI2 and iloprost on the contents of high energy phosphates, cAMP, glycolytic metabolites and on cardiac performance was investigated in open-chest dogs subjected to 3 h of ischaemia, induced by occlusion of the left anterior descending coronary artery. The administration of drugs for 2 h, starting 1 h after the onset of ischaemia, resulted in a normalization and an appreciable reduction in the loss of high energy phosphates in the non-ischaemic and ischaemic left ventricular muscle, respectively, leading to an improvement in the phosphate potential of the cardiac tissue. A reduction in the ischemia-induced rise in cAMP levels was observed, indicating a lower catecholamine overflow in the presence of these drugs. PGI2 and iloprost in the dose employed significantly decreased cardiac preload, which was found to be elevated in the untreated animals after coronary artery ligation. The observed effect of PGI2 and its mimetic on the haemodynamics, as well as on myocardial cAMP and high energy phosphate levels of the heart, may be considered helpful in the phase of temporary imbalance between energy demand and supply during acute ischaemia.

Beneficial effect of beraprost, a prostacyclin‐mimetic agent, on post‐hypoxic recovery of cardiac function and metabolism in rabbit isolated hearts

“…Inhibition of thromboxane A2 production or blocking its receptor during ischaemia has been demonstrated to protect the myocardium against ischaemia/reperfusion injury as evidenced by prevention of an increase in lactate release from the heart, limitation of cardiac risk area and decrease in reperfusion-induced arrhythmias (Sakai et al, 1982;Thiemermann & Schrbr, 1984;Grover et al, 1988;1990;Mehta et al, 1990;Lesenefsky et al, 1990). Furthermore, several investigators have found that treatment with iloprost, a prostacyclinmimetic agent, improved myocardial metabolism during ischaemia and resulted in an enhanced recovery of cardiac function (Van Glist et al, 1983;Giessen et al, 1986;Pissarek et al, 1987;Chiariello et al, 1988;Ferrari et al, 1988). These results suggest an involvement of prostacyclin-mimetics in the enhancement of post-hypoxic or post-ischaemic functional and metabolic improvement of the myocardium.…”

“…Since these agents decrease energy demand during hypoxia or ischaemia by suppression of cardiac contractility, they protect the myocardium from depletion of high-energy phosphate levels, that is, they have an energy sparing effect (Nayler et al, 1978). Prostacyclin and iloprost have been shown to preserve high-energy phosphates in the heart following coronary artery ligation (Pissarek et al, 1987). Thus, it is conceivable that prostacyclin and its mimetic agent have an energy-sparing effect on hypoxic or ischaemic myocardium.…”

“…shown that stable prostacyclin-mimetic agents, such as iloprost and nileprost, improved recovery of cardiac energy metabolism after ischaemia and reduced infarct size after-ligation of the coronary artery (Schror et al, 1981a;Thiemermann & Schror, 1984;De Langen et al, 1985;Darius et al, 1986;Pissarek et al, 1987;Ferrari et al, 1988;Chiariello et al, 1988). Furthermore, it has been shown that thromboxane A2 antagonists and inhibition of thromboxane A2 synthesis are capable of reducing myocardial infarct size and inhibiting lactate release (Sakai et al, 1982;Grover et al, 1988).…”

Changes by short-term hypoxia in the membrane properties of pyramidal cells and the levels of purine and pyrimidine nucleotides in slices of rat neocortex; effects of agonists and antagonists of ATP-dependent potassium channels

“…Extract preparation. The extract was prepared as previously described (Pissarek et al 1987). The slices were homogenized under addition of 0.5 M perchloric acid in a mortar cooled with liquid nitrogen.…”