title: Aldosterone and testosterone: two steroid hormones structurally related but with opposite electrophysiological properties during myocardial ischemia-reperfusion.
abstract: Steroid hormones appear to be a key factor in the gender differences in the rates and severity of cardiovascular diseases. Aldosterone and testosterone have typical steroid ring structure, but despite this, they demonstrate very different properties. During acute myocardial ischemia-reperfusion, the deleterious impact of aldosterone is now well established. Conversely, the electrophysiological impact of testosterone in this context remained unknown. We used female rabbit in vitro models and standard microelectrode technique including right ventricle mimicking the 'border zone' existing between normal and ischemic/reperfused areas and isolated right ventricle experiments to assess the acute electrophysiological impact of both aldosterone and testosterone. During ischemia-reperfusion, acute superfusion of 10 and 100 nmol/L testosterone decreased normoxic and reperfused action potential duration at 90% (APD90 ), systematically induced conduction blocks, and decreased APD90 dispersion between ischemic and nonischemic areas (from 98 ± 4 to 57 ± 7 ms and 66 ± 3 ms, for, respectively, testosterone 10 and 100 nmol/L, P < 0.05). Testosterone 10 and 100 nmol/L concomitantly decreased sustained premature ventricular contraction (PVC) occurrence (from 55 to 0%, P < 0.05). Conversely, aldosterone 10 and 100 nmol/L increased normoxic and reperfused APD90 , APD90 dispersion, and reperfusion-induced PVCs. Furthermore, testosterone demonstrated cycle length-dependent effects on APD90 for high heart rate, whereas aldosterone did not exhibit any significant effect compared with controls. During acute myocardial ischemia-reperfusion, acute superfusion of physiological concentrations of testosterone seemed to be anti-arrhythmic by removing a pro-arrhythmic substrate (APD90 dispersion), inducing conduction blocks and decreasing triggered activities (PVC occurrence). Further experiments are warranted to confirm our results.
authors: Department of Pharmacology, CHU de Caen, Caen, F-14000, France.|Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14000, France.|Medical School, Université de Caen Basse-Normandie, Caen, F-14000, France.
authors: Joachim
authors: J
authors: Alexandre
authors: Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14000, France.|Medical School, Université de Caen Basse-Normandie, Caen, F-14000, France.|Department of Cardiology, CHU de Caen, Caen, F-14000, France.
authors: Paul
authors: P
authors: Milliez
authors: Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14000, France.|Medical School, Université de Caen Basse-Normandie, Caen, F-14000, France.
authors: René
authors: R
authors: Rouet
authors: Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14000, France.|Medical School, Université de Caen Basse-Normandie, Caen, F-14000, France.|Department of Nuclear Medicine, CHU de Caen, Caen, F-14000, France.
authors: Alain
authors: A
authors: Manrique
authors: Université de Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14000, France.|Medical School, Université de Caen Basse-Normandie, Caen, F-14000, France.|Department of Biochemistry, CHU de Caen, Caen, F-14000, France.
authors: Stéphane
authors: S
authors: Allouche
authors: Department of Cardiovascular Sciences, Sapienza University, Rome, Italy.
authors: Gianfranco
authors: G
authors: Piccirillo
authors: Department of Cardiovascular Sciences, Sapienza University, Rome, Italy.
authors: Michele
authors: M
authors: Schiariti
authors: Department of Cardiovascular Sciences, Sapienza University, Rome, Italy.
authors: Paolo-Emilio
authors: PE
authors: Puddu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D054537:Atrioventricular Block / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D011817:Rabbits; D013739:Testosterone / Q000494:pharmacology*; D018879:Ventricular Premature Complexes / Q000188:drug therapy
chemical_list: D013739:Testosterone; D000450:Aldosterone
keywords: aldosterone; ischemia; sudden death; testosterone; ventricular arrhythmia