title: Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.
abstract: OBJECTIVE
  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.affiliation: Servicio de Cardiología, Hospital Clínico Universitario de Valencia, INCLIVA, Valencia, Spain; Departamento de Medicina, Universidad de Valencia-Estudi General, Valencia, Spain. Electronic address: Francisco.J.Chorro@uv.es.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Chorro
authors.affiliation: Departamento de Medicina, Universidad de Valencia-Estudi General, Valencia, Spain.
authors.forename: Irene Del
authors.initials: ID
authors.lastname: Canto
authors.affiliation: Departamento de Fisiología, Universidad de Valencia-Estudi General, Valencia, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Brines
authors.affiliation: Departamento de Fisioterapia, Universidad de Valencia-Estudi General, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Such-Miquel
authors.affiliation: Departamento de Electrónica, Universidad Politécnica de Valencia, Valencia, Spain.
authors.forename: Conrado
authors.initials: C
authors.lastname: Calvo
authors.affiliation: Departamento de Fisiología, Universidad de Valencia-Estudi General, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Soler
authors.affiliation: Departamento de Fisioterapia, Universidad de Valencia-Estudi General, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zarzoso
authors.affiliation: Departamento de Enfermería, Universidad de Valencia-Estudi General, Valencia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Trapero
authors.affiliation: Departamento de Electrónica, Universidad Politécnica de Valencia, Valencia, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Tormos
authors.affiliation: Departamento de Fisiología, Universidad de Valencia-Estudi General, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Such
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D019808:Losartan / Q000494:pharmacology; D009206:Myocardium; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects; D013312:Stress, Physiological / Q000502:physiology*; D014693:Ventricular Fibrillation / Q000503:physiopathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D065128:Endothelin Receptor Antagonists; D062686:Epithelial Sodium Channel Blockers; D010456:Peptides, Cyclic; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D019808:Losartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C039614:ethylisopropylamiloride
keywords: Angiotensin inhibitors; Arrhythmia; Arritmia; Basic research; Biomechanical stress; Drugs; Electrofisiología; Electrophysiology; Endotelina; Endothelin; Estrés biomecánico; Fibrilación ventricular; Fármacos; Inhibidores de la angiotensina; Investigación básica; Mapeo; Mapping; Miocardio; Myocardium; Ventricular fibrillation