Skip Navigation LinksHome > August 2014 - Volume 64 - Issue 2 > Proarrhythmic Effects of Aldosterone During Myocardial Ische...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0000000000000097
Original Article

Proarrhythmic Effects of Aldosterone During Myocardial Ischemia–Reperfusion: Implication of the Sarcolemmal-KATP Channels

Alexandre, Joachim MD*,†; Puddu, Paolo-Emilio MD, PhD; Simard, Christophe PhD; Hof, Thomas MS; Sallé, Laurent PhD†,§; Guinamard, Romain PhD†,§; Manrique, Alain MD, PhD†,§; Rouet, René PhD†,§; Beygui, Farzin MD, PhD*,§; Milliez, Paul MD, PhD*,†,§

Collapse Box

Abstract

Objective:

To assess the electrophysiological impact of aldosterone during myocardial ischemia–reperfusion.

Methods:

We used an in vitro model of “border zone” using rabbit right ventricle and standard microelectrodes.

Results:

Aldosterone (10 and 100 nmol/L) shortened ischemic action potential [action potential duration at 90% of repolarization (APD90), from 55 ± 3 to 39 ± 1 ms and 36 ± 3 ms, respectively, P < 0.05] and induced resting membrane potential (RMP) hyperpolarization in the nonischemic zone (from −83 ± 1 to −93 ± 7 mV and −94 ± 3 mV, respectively, P < 0.05) and in the ischemic zone during reperfusion (from −81 ± 2 to −88 ± 2 mV and −91 ± 2 mV, respectively, P < 0.05). Bimakalim, an ATP-sensitive potassium (KATP) channel opener, also induced RMP hyperpolarization and APD90 shortening. Aldosterone (10 and 100 nmol/L) increased APD90 dispersion between ischemic and nonischemic zones (from 96 ± 3 to 117 ± 5 ms and 131 ± 6 ms, respectively, P < 0.05) and reperfusion-induced severe premature ventricular contraction occurrence (from 18% to 67% and 75%, respectively, P < 0.05). Adding glibenclamide, a nonspecific KATP antagonist, to aldosterone superfusion abolished these effects different to sodium 5-hydroxydecanoate, a mitochondrial-KATP antagonist.

Conclusions:

In this in vitro rabbit model of border zone, aldosterone induced RMP hyperpolarization and decreased ischemic APD90 evoking the modulation of K+ currents. Glibenclamide prevented these effects different to 5-hydroxydecanoate, suggesting that sarcolemmal-KATP channels may be involved in this context.

Copyright © 2014 by Lippincott Williams & Wilkins

Follow Us!

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.