Abstract | INTRODUCTION: MATERIALS AND METHODS: We used rabbit in vitro models and standard microelectrode technique to assess the electrophysiological impact of PC during myocardial ischemia-reperfusion, including right ventricle mimicking the "border zone" existing between normal and ischemic/reperfused areas (1 µmol/L, 10 and 100 nmol/L), isolated right ventricle, and sinoatrial node (SAN) experiments (1 µmol/L, respectively). RESULTS: During ischemia-reperfusion, acute superfusion of PC 100 nmol/L prevented the increase in action potential (AP) duration at 90% of repolarization (APD90) dispersion between ischemic and nonischemic areas and in VAs occurrence induced by aldosterone 10 nmol/ L (86 ± 3 vs 114 ± 4 milliseconds for aldosterone alone, P < .05). Potassium canrenoate also induced conduction blocks and significantly decreased Vmax during simulated ischemia (from 25 ± 5 to 12 ± 4, 14 ± 3, and 14 ± 5 V/s, respectively, for PC 1 µmol/L, 100, and 10 nmol/L, P < .05). Potassium canrenoate 1 µmol/L demonstrated cycle length (CL)-dependent effects on APD90 and on Vmax, and it also reduced SAN beating CL (from 446 ± 28 to 529 ± 24 millisecond, P < .05). CONCLUSION: Our experimental study highlights new evidence for an antiarrhythmic impact of PC during myocardial ischemia-reperfusion via multiple channels modulation. These results are in line with recent clinical trials suggesting that an early MR blockade in STEMI may be preventive of VAs.
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Authors | Joachim Alexandre, Farzin Beygui, Paolo-Emilio Puddu, Alain Manrique, René Rouet, Paul Milliez |
Journal | Journal of cardiovascular pharmacology and therapeutics
(J Cardiovasc Pharmacol Ther)
Vol. 20
Issue 3
Pg. 313-21
(May 2015)
ISSN: 1940-4034 [Electronic] United States |
PMID | 25389106
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author(s) 2014. |
Chemical References |
- Anti-Arrhythmia Agents
- Mineralocorticoid Receptor Antagonists
- Canrenoic Acid
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Topics |
- Action Potentials
(drug effects)
- Animals
- Anti-Arrhythmia Agents
(pharmacology)
- Canrenoic Acid
(pharmacology)
- Female
- Male
- Mineralocorticoid Receptor Antagonists
(pharmacology)
- Myocardial Reperfusion
- Rabbits
- Sinoatrial Node
(drug effects, physiology)
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