Effects of adenine nucleotide analogues on myocardial dysfunction during reperfusion after ischemia in dogs

J Cardiovasc Pharmacol. 1996 Aug;28(2):264-70. doi: 10.1097/00005344-199608000-00013.

Abstract

We examined effects of adenine nucleotide on ischemic myocardial stunning in dogs. Pentobarbitalanesthetized open-chest dogs were subjected to 20-min ligation of the left anterior descending coronary artery (LAD), followed by reperfusion for 30 min. Either saline, 5 mM 8-bromo-5'-AMP (tributyryl-AMP), or 30 mM N6, 2', 3'-tributyryl-5'-AMP (tributyryl-AMP), 5 mM 5-amino-4-imidazole carboxamide riboside (AICAr) as a positive reference, was infused at 0.1 ml/kg/min in the left femoral vein throughout the experiment. The myocardial contractile function was measured by ultrasonometry. The tissue levels of high-energy phosphates in the reperfused heart were determined. Myocardial contractile function assessed by % segment shortening (%SS) in the saline-infused group decreased during ischemia and returned toward the preischemic level during reperfusion but incompletely. A significant improvement in the %SS during reperfusion was observed in the 8-bromo-AMP- and AICAr-infused groups but not in the tributyryl-AMP-infused group. The magnitude of the protective effect of the drugs on myocardial contractility during reperfusion was 8-bromo-AMP > AICAr > tributyryl-AMP = saline. Only in the 8-bromo-AMP-infused group were the levels of ATP, ADP, and total adenine nucleotides in the reperfused heart significantly higher than those in the saline-infused group. The present result indicates that 8-bromo-AMP improves the ability of the heart to recover from ischemia and reperfusion associated with a significant restoration of ATP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenine Nucleotides / pharmacology*
  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Carbohydrate Metabolism
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / physiopathology
  • Coronary Circulation / drug effects
  • Coronary Circulation / physiology
  • Dogs
  • Female
  • Hemodynamics / drug effects
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Ischemia / physiopathology*
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / physiopathology*
  • Myocardium / metabolism
  • Ribonucleotides / pharmacology

Substances

  • Adenine Nucleotides
  • Ribonucleotides
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Aminoimidazole Carboxamide
  • Adenosine Monophosphate
  • tributyryladenosine monophosphate
  • AICA ribonucleotide