Blockade of adenosine receptors with aminophylline limits ischemic preconditioning in human beings

Am Heart J. 2001 Sep;142(3):E4. doi: 10.1067/mhj.2001.117133.

Abstract

Background: Ischemic preconditioning is characterized by the limitation of infarct size or ischemic signs after one or more brief episodes of ischemia, a process that probably involves stimulation of adenosine receptors. One human model of ischemic preconditioning is repetitive occlusion of a coronary artery during angioplasty. By using this method of inducing ischemia, we tested the hypothesis that blockade of adenosine receptors with aminophylline would abolish ischemic preconditioning in human beings.

Methods: Twenty-six patients undergoing angioplasty were randomly assigned to receive either aminophylline (6 mg/kg IV) or placebo before repetitive coronary occlusion (two 2-minute occlusions separated by 5 minutes). ST-segment changes on the surface electrocardiogram were used as a measure of myocardial ischemia. Serum theophylline levels and the conduction response to an intravenous bolus of adenosine were used to assess the efficacy of adenosine receptor blockade.

Results: Repetitive coronary occlusion resulted in a reduction in ST-segment shift in 9 of 13 patients given placebo. In contrast, 9 of 13 patients receiving aminophylline had an increase in ST-segment shift on the second occlusion (P =.002). Patients receiving aminophylline (mean serum theophylline level of 8.38 +/- 0.45 mg/dL) did not have significant conduction block with intravenous adenosine.

Conclusions: Repetitive coronary occlusion reduces the signs of ischemia in human beings, a process limited by blockade of adenosine receptors.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aminophylline / pharmacology*
  • Angioplasty
  • Cardiotonic Agents / pharmacology*
  • Coronary Disease / pathology*
  • Electrocardiography
  • Female
  • Humans
  • Ischemic Preconditioning, Myocardial*
  • Male
  • Middle Aged
  • Myocardial Ischemia / physiopathology*
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1 / physiology*
  • Theophylline / analysis

Substances

  • Cardiotonic Agents
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Aminophylline
  • Theophylline