Tadashi Kamikawa

Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris

The effects of coenzyme Q10(CoQ10) on exercise performance were studied in 12 patients, average age 56 years, with stable angina pectoris. The study involved a double-blind, placebo-controlled, randomized, crossover protocol, using multistage treadmill exercise tests. CoQ10(150 mg/day in 3 daily doses) was administered orally for 4 weeks, tended to reduce anginal frequency from 5.3 +/- 4.9 to 2.5 +/- 3.3 attacks for 2 weeks and nitroglycerin consumption from 2.6 +/- 2.8 to 1.3 +/- 1.7 tablets for 2 weeks compared with patients receiving the placebo, but the reduction was not statistically significant. Exercise time increased from 345 +/- 102 seconds with placebo to 406 +/- 114 seconds during CoQ10 treatment (p less than 0.05). The time until 1 mm of ST-segment depression occurred increased from 196 +/- 76 seconds with placebo to 284 +/- 104 seconds during CoQ10 treatment (p less than 0.01). During the exercise test, ST-segment depression, heart rate and pressure-rate product at the same and at the maximal workload showed no significant difference between patients after placebo and CoQ10 administration. The average CoQ10 plasma concentration increased from 0.95 +/- 0.48 microgram/ml to 2.20 +/- 0.98 microgram/ml after CoQ10 treatment. This increase was significantly related to the increase in exercise duration (r = 0.68, p less than 0.001). Only 1 patient had a loss of appetite, but continued therapy. This study suggests that CoQ10 is a safe and promising treatment for angina pectoris.

The effects of nitroglycerin on cyclic nucleotides in the coronary artery invivo

Abstract We examined the effects of nitroglycerin (NGL) on cyclic AMP (c-AMP) and cyclic GMP (c-GMP) in the coronary artery at 15 sec, 30 sec, 60 sec, and 3 min after the injection of NGL (0.02 mg/kg i.v.) in vivo. The relaxant effect of NGL was significantly correlated to an increase in the c-GMP concentration of the coronary artery. The c-AMP concentrations were not significantly changed at any time during the time response studies. We observed purely in vivo that there was a close correlation between an increase in c-GMP concentration after treatment with NGL and relaxation of the canine coronary artery. This study suggests that intracellular c-GMP may be involved with the biologic events leading to smooth muscle relaxation.

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.

Effects of L-Carnitine on Tissue Levels of Free Fatty Acid, Acyl CoA, and Acylcarnitine in Ischemic Heart

In order to evaluate the protective effects of L-carnitine on ischemic myocardium, its effects on tissue levels of free fatty acid (FFA), acyl CoA, acyl carnitine, and adenosine triphosphate (ATP) were studied in ischemic dog hearts. Myocardial ischemia was induced by the ligation of left anterior descending coronary artery for 15 min. L-Carnitine (100 mg/kg) was administered intravenously prior to coronary ligation. In ischemic myocardium, tissue levels of free carnitine and ATP decreased, whereas long-chain acyl carnitine, long-chain acyl CoA, and FFA increased. Pretreatment of L-carnitine prevented the decrease in free carnitine and ATP and the increase in long-chain acyl carnitine and long-chain acyl CoA. A positive correlation was observed between ATP and free carnitine. On the other hand, a negative correlation was observed not only between ATP and the ratio of long-chain acyl CoA to free carnitine but also between ATP and the ratio of long-chain acyl carnitine to free carnitine. These results suggest that L-carnitine has protective effects on ischemic myocardium, probably by preventing the accumulation of long-chain acyl carnitine and long chain acyl CoA.

Changes of Plasma Levels of TRH and Its Target Hormones by Two Hour Constant Intravenous Infusion of TRH Tartrate in Man

Constant iv infusion of TRH tartrate for 2 hours was administered to normal men in a dosage of 0.5 (n=4), 1.0 (n=2) and 2 (n=4) mg/120 minutes. Measurements at every 15 minutes were performed for plasma levels of TRH, TSH, Thyroxine (T4) and Triiodothyronine (T3) by radioimmunoassay. Plasma levels of TRH increased promptly and stayed at the same levels until the end of the infusion. The Mean Clearance Rate (MRC), Half-life and Volume of Distribution of TRH were respectively, 4.62 +/- 0.53 L/min. (M +/- SE), 17.8 +/- 3.8 minutes and 112 +/- 15 L in the 0.5 mg administered group and 6.38 +/- 2.50 L/min., 9.0 +/- 1.4 minutes and 82 +/- 30 L in the 2 mg administered group. Plasma levels of TRH increased in two phases, and increments of plasma TSH were dose dependable to the dosage of TRH. Plasma levels of T4 increased gradually in the course of TRH infusion and stayed at high levels even in the withdrawal phase of TRH. Plasma levels of T3 increased markedly during and after the TRH infusion in the 0.5 mg administered group, while increments of plasma T3 were minute in the 2 mg administered group. From the above data, it is suggested that the amount of TRH production in man, which is much more than has previously been reported, may indicate the existence of an extrahypothalamic synthesis of TRH in man.