Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion

Abstract

In control anaesthetized baboons subjected to 30 min occlusion of the left anterior descending coronary artery, followed by 5.5 h reperfusion, total plasma levels for creatine kinase (CK) and lactate dehydrogenase (LDH) were markedly elevated in a time-related manner. In a second group of baboons pretreated 10min prior to ischaemia with ranolazine [(±+N{2,6-dimethyl-phenyl)-4[2-hydroxy-342-methoxyphenoxy)propyl]-1-piperazine acetamide dihydrochloride; RS43285-193] at 500pgkg-1 i.v., followed by continuous infusion of SO gkg-1 min-1, neither enzyme was significantly elevated at any time point.Similarly, serum levels of the cardiospecific isoenzyme CK2 were 8 fold greater in the controls than in the ranolazine-treated animals at 6h. The results indicate that ranolazine pretreatment abolished cardiac enzyme release over a 5.5 h reperfusion period, indicating a potential protective effect.

Evidence that ranolazine behaves as a weak β 1 - and β 2 -adrenoceptor antagonist in the rat cardiovascular system

“…Ranolazine has demonstrated myocardial anti-ischaemic activity in a number of in vivo (Allely and Alps 1990;Allely et al 1993) and in vitro McCormack et al 1996) preparations from several different species. Initial clinical findings have suggested that ranolazine is an orally active agent potentially useful for angina pectoris therapy (Cocco et al 1992).…”

A Study of the Effects of Ranolazine Using Automated Quantitative Analysis of Serial Myocardial Perfusion Images

“…In an animal model, ranolazine increases myocardial blood flow (MBF), possibly because inhibition of late sodium current results in a decrease in left ventricular (LV) stiffness, which in turn decreases extravascular compressive forces on coronary microcirculation and thereby improves MBF (11)(12)(13)(14). Such an improvement in MBF is likely to contribute to the antianginal effects of ranolazine.…”

Protective effects of ranolazine in guinea‐pig hearts during low‐flow ischaemia and their association with increases in active pyruvate dehydrogenase

“…Ranolazine has also been shown to be remarkably effective in preventing myocardial enzyme release in an intact primate model of ischaemia with reperfusion (Allely & Alps, 1990). It has been suggested that ranolazine may alleviate the symptoms of transient myocardial ischaemia by altering substrate utilization (Allely et al, 1987).…”