Masaaki Abe

Effect of palmitoyl carnitine on Na+, K+-ATPase and adenylate cyclase activity of canine myocardial sarcolemma

The accumulation of long chain of acyl carnitine, which is thought to exaggerate myocardial ischemic damage, has been demonstrated in ischemic myocardium. The purpose of this study was to determine the effect of palmitoyl carnitine on the Na+, K+-ATPase and adenylate cyclase activity of myocardial sarcolemma in vitro. Controversial views exist at present regarding the effect of palmitoyl carnitine on Na+, K+-ATPase. Wood et al. [23] observed that palmitoyl carnitine inhibited the activity of Na+, K+-ATPase but this inhibition was not observed by Owens et al. [17]. We did observe an inhibition of Na+, K+-ATPase by palmitoyl carnitine. The 50% inhibition of the maximum activity was observed at a palmitoyl carnitine concentration of 110 microM and complete inhibition at 160 microM. Adenylate cyclase activity was inhibited by palmitoyl carnitine irrespective of the assay conditions. The (isoproterenol + GTP)-stimulated activity, fluoride-stimulated activity and basal activity with Mg-ATP or Mn-ATP as a substrate were all inhibited though to varying degrees. The 50% inhibition of adenylate cyclase activity was observed at 84 microM, 94 microM, 200 microM and 105 microM of palmitoyl carnitine in the above mentioned order. The inhibition curve showed a shoulder or even a peak at about 75 microM of palmitoyl carnitine. It is suggested that elevated levels of palmitoyl carnitine in ischemic myocardium may play a role in inhibiting sarcolemmal function.

Effects of L-carnitine on action potential of canine papillary muscle during hypoxic perfusion

Under hypoxic (95% N2 + 5% CO2) perfusion, electrophysiological effects of L-carnitine on canine papillary muscles were studied using standard microelectrode techniques. During hypoxic perfusion for 60 min, resting membrane potential (RMP), action potential amplitude (APA) and maximum upstroke velocity of phase 0 were decreased, and action potential duration (APD) and effective refractory period (ERP) were shortened. Application of L-carnitine 25 mM under hypoxic perfusion increased RMP and APA and prolonged APD and ERP significantly. As effects of L-carnitine during hypoxic perfusion might be that of hypertonicity, effects of sucrose of the same tonicity as L-carnitine were studied under hypoxia. Sucrose did not cause significant changes on various parameters of action potential compared with hypoxic perfusion. It was suggested that the increase in RMP, and the prolongation of APD and ERP might be caused by an increase in intracellular ATP content. The findings in this study could be an explanation of possible antiarrhythmic effects of L-carnitine.

Antiarrhythmic and myocardial metabolic effects of verapamil during coronary arterial reperfusion

ANTIARRHYTHMIC AND MYOCARDIAL METABOLIC EFFECTS OF VERAPAMIL DURING CORONARY ARTERIAL REPERFUSION. A. Kobayashi, Y. Suzuki, Y. Masumura, H. Hayashi, M. Abe, K. Nishihara, T. Kamikawa, N. Yamazaki. Third Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan To determine the effects of verapamil(VP) on ventricular fibrillation(Vf) and free fatty acids(FFA) metabolism during coronary arterial occlusion for 40 min and reperfusion for 15 min. VP(O.lmg/kg) was administered in 5 min before occlusion and followed by an infusion of O.Olmg/kg /min during examination.ECGs were recorded throughout the experiment.Myocardial samples were obtained from both the ischemic and nonischemic zones after reperfusion and meas ured ATP,free carnitine(FC),long chain acyl carnitine(LC) ,long chain acyl CoA and FFA.VP significantly reduced the incidence rate of Vf. ATP and FC levels in the ischemic zone in the VP group were significantly higher than those in the control. LC levels in both the ischemic and nonischemic zones in the VP group were significantly lower. This suggests that VP has protective effects on Vf and on FFA metabolic changes after coronary arterial reperfusion