Tai Nakamura

Comparison of the effects of nifedipine and nisoldipine on coronary vasoconstriction in the Langendorff-perfused rat heart.

By using Langendorff-perfused rat hearts, we compared the relaxant effects of two dihydropyridine calcium antagonists (nifedipine and nisoldipine) on the coronary vasculature. Hearts were perfused at a constant flow rate (13 ml/min), and the coronary perfusion pressure was monitored to assess vasoconstriction and relaxation. Administration of 5 nM endothelin significantly increased the perfusion pressure within 5 min, and it did not decrease during the subsequent 10-min washout period. Washout with 1 nM nisoldipine or 10 nM nifedipine almost completely normalized the perfusion pressure. Administration of a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (100 microM), elevated the perfusion pressure at 5 min. When 1 nM nifedipine was added to the perfusate, it failed to decrease the pressure, but 10 and 100 nM nifedipine partly decreased it (96.4+/-8.2 and 87.0+/-8.8 mm Hg for 10 and 100 nM, respectively). Nisoldipine alleviated the pressure elevation almost completely at 10 nM (60.0+/-5.2 mm Hg). The vasodilatory effect of nisoldipine was also approximately 10 times more potent than that of nifedipine when coronary vasoconstriction was induced by hypoxia-reoxygenation. These results suggest that nisoldipine has a stronger effect than nifedipine at the organ level, which does not depend on the cause of coronary vasoconstriction.

Hydrogen peroxide-induced enhancement of prostanoid release and myocardial damage by its washout in isolated rat heart

Abstract Hydrogen peroxide (H 2 O 2 ) contributes to the development of reperfusion injury. The aim of this study was to characterize the effects of H 2 O 2 on cardiac function, autacoid release and myocardial damage. Rat hearts were Langendorff-perfused with Krebs solution containing 70, 200 or 700 μM H 2 O 2 for 30 min, then washed out with normal Krebs solution. The left ventricular pressure, heart rate and coronary perfusion pressure were monitored, released prostanoid and NO was quantified and the activity of released glutamic oxaloacetic transaminase (GOT) was estimated. H 2 O 2 (70 μM) significantly increased prostacyclin release with no evidence of myocardial damage. H 2 O 2 (200 μM) stimulated the release of all the prostanoids quantified markedly without affecting NO release. GOT release did not increase during H 2 O 2 perfusion, but did increase after washout. Inhibition of prostanoid release with indomethacin did not affect the washout-induced increase in GOT release. These results indicate that a low concentration of H 2 O 2 stimulates prostanoid release without affecting myocardial contraction, while higher concentrations damage the heart indirectly. The mechanism of the washout-induced myocardial damage is not clear yet, but the H 2 O 2 -induced change in prostanoid release did not seem to be responsible for the damage.

Clinical Evaluation of Celiprolol in the Treatment of Atrial Tachyarrhythmias

SummaryThe results of the Cardiac Arrhythmia Suppression Trial warn against the use of class Ia and Ic antiarrhythmic agents as first-line therapy for arrhythmia. The objective of the present study was to evaluate the efficacy of celiprolol, a β-blocker, in patients with supraventricular arrhythmia. Celiprolol (200 mg/day) was administered for a mean duration of 90 days (range: 32 to 128 days) to 30 patients with supraventricular arrhythmia, including 7 with chronic atrial fibrillation associated with bradycardia, 18 with paroxysmal atrial fibrillation, and 5 with premature atrial contraction (PAC). The antiarrhythmic effect of celiprolol was assessed based on changes in symptoms and heart rate determined by Holter ECG. After celiprolol therapy, arrhythmic symptoms improved in 60% of the patients. The post-treatment Holter ECG showed a decrease in the daily maximum, but not minimum, heart rate, a good control of heart rate in patients with atrial fibrillation, and a decrease of PACs. Importantly, bradycardia improved even in patients with chronic atrial fibrillation who concomitantly received digitalis. Celiprolol exerted an adequate antihypertensive effect in hypertensive patients but did not affect normal blood pressure. In conclusion, celiprolol may be used as first-line therapy for the treatment of patients with supraventricular arrhythmia.