[Cardioprotective mechanism of ischemic preconditioning is impaired by postinfarct ventricular remodeling through angiotensin II type 1 receptor activation]

J Cardiol. 2001 Feb;37(2):112-3.
[Article in Japanese]

Abstract

Background: Activation of protein kinase C-linked receptors and subsequent opening of the mitochondrial adenosine triphosphate-sensitive K+ (mitoKatp) channel is crucial in preconditioning. This study examined whether post-infarct ventricular remodeling interferes with the preconditioning mechanism.

Methods and results: Two weeks before isolation of hearts, rabbits underwent a sham operation or coronary ligation (COL) to induce remodeling. Isolated buffer perfused hearts were subjected to 30-min global ischemia/2-hr reperfusion, and infarct size was expressed as a percentage of the left ventricle (%I/LV), from which the scarred infarct by COL was excluded. Although %I/LV was similar in sham-operated and remodeled hearts (52.9 +/- 6.5% vs 45.8 +/- 5.2%), preconditioning with 2 episodes of 5-min ischemia protected sham-operated but not remodeled hearts (%I/LV = 18.1 +/- 2.5% vs 54.8 + 2.9%, p < 0.05). Infusion of valsartan (10 mg/kg/day; Val), an angiotensin II type 1 receptor blocker, for 2 weeks after COL prevented the ventricular remodeling and preserved the response to preconditioning (%I/LV = 27.4 +/- 3.8%), though Val alone did not change %I/LV. Diazoxide, a mitoKatp channel opener, protected both sham-operated and remodeled hearts (%I/LV = 14.1 +/- 3.1% and 8.3 +/- 3.6%).

Conclusions: The myocardium remodeled after infarction is refractory to preconditioning, which is probably due to interruption of cellular signaling by preconditioning upstream of mitoKatp channels. An angiotensin II type 1 receptor blocker is beneficial not only for suppression of ventricular remodeling but also for preservation of the preconditioning mechanism.

Publication types

  • English Abstract

MeSH terms

  • Angiotensin Receptor Antagonists
  • Animals
  • Ischemic Preconditioning, Myocardial*
  • Myocardial Infarction / physiopathology
  • Rabbits
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin / physiology*
  • Tetrazoles / pharmacology
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Valsartan
  • Ventricular Remodeling / physiology*

Substances

  • Angiotensin Receptor Antagonists
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin
  • Tetrazoles
  • Valsartan
  • Valine