Blockade of adenosine receptors with aminophylline limits ischemic preconditioning in human beings.
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.
Schaefer
S
S
Division of Cardiovascular Medicine, University of California, Davis CA 95616, USA.
Correa
S D
SD
Valente
R J
RJ
Laslett
L J
LJ
D000628:Aminophylline / Q000494:pharmacology*; D017130:Angioplasty; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003327:Coronary Disease / Q000473:pathology*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000503:physiopathology*; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013806:Theophylline / Q000032:analysis
D002316:Cardiotonic Agents; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D000628:Aminophylline; D013806:Theophylline