A Novel Cardioprotective Agent, JTV-519, Is Abolished by Nitric Oxide Synthase Inhibitor on Myocardial Metabolism in Ischemia-Reperfused Rabbit Hearts

Abstract

We investigated the effect of a novel cardioprotective agent, JTV-519, with or without a nitric oxide synthase inhibitor, L-NAME, on the myocardial metabolism and contraction during ischemia and reperfusion by means of phosphorus 31-nuclear magnetic resonance ( lated compounds during the ischemic period, could be blamed. Nonetheless, even in cases in which ATP does not decrease and creatine phosphate recovers rapidly after short periods of ischemia, stunning is already present. The fact that the stunned myocardium can respond well to inotropic stimulation by the dopamine, isoproterenol, calcium infusion, epinephrine, or postextrasystolic potentiation suggests that stunning represents a lack of available intracellular calcium, a failure of uptake of calcium by the sarcoplasmic reticulum, or a failure of the contractile proteins to respond to normal calcium concentration (2). Kusuoka et al. (3,4)

Cardioprotection by Metformin Is Abolished by a Nitric Oxide Synthase Inhibitor in Ischemic Rabbit Hearts.

“…The events in the transition from ischemia to infarction are very complex and cannot simply be ascribed to a depletion of ATP (13,14). Rather, the depletion of ATP should be seen as a marker of 1) the severity of the ischemic process; 2) a depressed rate of anaerobic glycolysis in severely ischemic tissue that is caused by an accumulation of glycolytic end-products; 3) an inhibited lipid metabolism with an accumulation of intermediates such as acylcoenzyme A (acyl CoA) and acyl carnitine, with an inhibition of mitochondrial metabolism; and 4) an accumulation of intercellular calcium with ischemic contracture and the utilization of ATP.…”

Cardioprotection with pioglitazone is abolished by nitric oxide synthase inhibitor in ischemic rabbit hearts–comparison of the effects of pioglitazone and metformin

“…The events in the transition from ischemia to infarction are very complex and cannot simply be related to the depletion of ATP [26,27]. Rather, the depletion of ATP should be seen as a marker of (1) the severity of the ischemic process, (2) a depressed rate of anaerobic glycolysis in severely ischemic tissue, which is caused by an accumulation of glycolytic end products, (3) an inhibited lipid metabolism with an accumulation of intermediates such as acyl CoA and acyl carnitine, with an inhibition of mitochondrial metabolism, and (4) an accumulation of intercellular calcium with ischemic contracture and the utilization of ATP.…”

Effects of K-201 on the calcium pump and calcium release channel of rat skeletal muscle

“…The drug has been reported to have a very strong antiarrhythmic effect by reversing atrial fibrillation in a canine sterile pericarditis model [16]. It has also been reported that the drug exhibits significant potential for improving myocardial relaxation during ischemia, accompanied by the inhibition of the decrease in the cellular ATP level [13]. The involvement of FKBP 12.6 (FK-506 binding protein, calstabin2) suggested the importance of the calcium handling system in these cardioprotective effects [31,32].…”