BACKGROUND:Elevated plasma aldosterone levels represent an independent risk factor for increased mortality in congestive heart failure. Sudden cardiac deaths contribute substantially to the excessive mortality in congestive heart failure and so does atrial fibrillation as one of the major causes of stroke in elderly persons. So far, the electrophysiological properties of aldosterone have not been thoroughly characterized. In the present study, the effects of aldosterone on intracardiac monophasic action potentials were investigated in humans. METHODS AND RESULTS:Monophasic action potentials were recorded in six patients with supraventricular arrhythmias. Eleven ml of 0.9% NaCl (placebo) were injected intravenously, and monophasic action potentials recorded for 10 min. Thereafter, aldosterone (0.5 mg in 0.9% NaCl) was injected and recording of monophasic action potentials continued as previously. The mean action potential duration at 90% repolarization was calculated for the entire 10-min period of each treatment. All patients were in sinus rhythm and had normal electrolyte status. In the placebo period, mean MAPd90 was 287+/-22 ms (mean+/-S.D.), and 299+/-25 ms following aldosterone (P<0.02). After adjustment for heart rate, the difference remained statistically significant (P<0.01). The maximal effect of aldosterone was seen 4-6 min after injection. CONCLUSION:Aldosterone increases monophasic action potential duration within minutes after intravenous application. Therefore, this effect is likely to be mediated nongenomically. It may be hypothesized that aldosterone exerts its unfavorable effects partly via altering myocardial repolarization.
RCT Entities:
BACKGROUND: Elevated plasma aldosterone levels represent an independent risk factor for increased mortality in congestive heart failure. Sudden cardiac deaths contribute substantially to the excessive mortality in congestive heart failure and so does atrial fibrillation as one of the major causes of stroke in elderly persons. So far, the electrophysiological properties of aldosterone have not been thoroughly characterized. In the present study, the effects of aldosterone on intracardiac monophasic action potentials were investigated in humans. METHODS AND RESULTS: Monophasic action potentials were recorded in six patients with supraventricular arrhythmias. Eleven ml of 0.9% NaCl (placebo) were injected intravenously, and monophasic action potentials recorded for 10 min. Thereafter, aldosterone (0.5 mg in 0.9% NaCl) was injected and recording of monophasic action potentials continued as previously. The mean action potential duration at 90% repolarization was calculated for the entire 10-min period of each treatment. All patients were in sinus rhythm and had normal electrolyte status. In the placebo period, mean MAPd90 was 287+/-22 ms (mean+/-S.D.), and 299+/-25 ms following aldosterone (P<0.02). After adjustment for heart rate, the difference remained statistically significant (P<0.01). The maximal effect of aldosterone was seen 4-6 min after injection. CONCLUSION:Aldosterone increases monophasic action potential duration within minutes after intravenous application. Therefore, this effect is likely to be mediated nongenomically. It may be hypothesized that aldosterone exerts its unfavorable effects partly via altering myocardial repolarization.
Authors: Wenxia Chai; Ingrid M Garrelds; Udayasankar Arulmani; Regien G Schoemaker; Jos M J Lamers; A H Jan Danser Journal: Br J Pharmacol Date: 2005-07 Impact factor: 8.739