Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.

Abstract

INTRODUCTION AND OBJECTIVES:

Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na(+)/H(+) exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch.

METHODS:

Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 μM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 μM, n = 9), and during perfusion with the Na(+)/H(+) exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 μM, n = 9).

RESULTS:

EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and EIPA=22% [P<.001]). During stretch, the activation maps were less complex (P<.0001) and the spectral concentration of the arrhythmia was greater (greater regularity) in the EIPA series: control=18 (3%); EIPA = 26 (9%) (P < .02); losartan=18 (5%) (not significant); and BQ-123=18 (4%) (not significant).

CONCLUSIONS:

The Na(+)/H(+) exchanger inhibitor EIPA attenuated the electrophysiological effects responsible for the acceleration and increased complexity of ventricular fibrillation induced by acute myocardial stretch. The angiotensin II receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects.

• Authors: Francisco J Chorro, Irene Del Canto, Laia Brines, Luis Such-Miquel, Conrado Calvo, Carlos Soler, Manuel Zarzoso, Isabel Trapero, Álvaro Tormos, Luis Such
• Journal: Revista espanola de cardiologia (English ed.) (Rev Esp Cardiol (Engl Ed)) Vol. 68 Issue 12 Pg. 1101-10 (Dec 2015) ISSN: 1885-5857 [Electronic] Spain
• PMID: 25985899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Endothelin Receptor Antagonists
• Epithelial Sodium Channel Blockers
• Peptides, Cyclic
• Sodium-Hydrogen Exchangers
• Amiloride
• Losartan
• cyclo(Trp-Asp-Pro-Val-Leu)
• ethylisopropylamiloride

Topics

• Amiloride (analogs & derivatives, pharmacology)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Endothelin Receptor Antagonists (pharmacology)
• Epithelial Sodium Channel Blockers (pharmacology)
• Heart (drug effects, physiology)
• Losartan (pharmacology)
• Myocardium
• Peptides, Cyclic (pharmacology)
• Rabbits
• Sodium-Hydrogen Exchangers (drug effects)
• Stress, Physiological (physiology)
• Ventricular Fibrillation (physiopathology)