Chronic dipyridamole therapy produces sustained protection against cardiac ischemia-reperfusion injury

Vincent M. Figueredo, Ivan Diamond, Hui Zhong Zhou, S. Albert Camacho

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Sustained protection against ischemia-reperfusion injury is not available for patients at risk for myocardial infarction who may require emergent reperfusion therapy. Whereas ischemic preconditioning and adenosinergic agents reduce myocardial injury, they are only effective when given immediately before ischemia or reperfusion. We recently found chronic ethanol exposure, an adenosine uptake inhibitor, produced sustained cardioprotection against ischemia-reperfusion injury. We now ask whether chronic dipyridamole therapy, a clinically usable nucleoside transport inhibitor, induces similar cardioprotection. Perfused hearts from guinea pigs, given dipyridamole (4 mg · kg-1 · day-1) in their water for 2-6 wk (n = 10 for each group), underwent ischemia-reperfusion. Injury was assessed by recovery of left ventricular developed (LVDP) and enddiastolic (LVEDP) pressures and creatine kinase release. During reperfusion, hearts from dipyridamole-treated animals (6 wk) had 74% higher LVDP, 28% lower LVEDP, and 61% lower creatine kinase release versus controls. Adenosine A1- receptor antagonism (8-cyclopentyl-1,3-dipropylxanthine; 200 nM) abolished the protection of dipyridamole but A2 antagonism (3,7-dimethyl-1- propargylxanthine; 10 mM) did not. Dipyridamole therapy produces sustained protection against ischemia-reperfusion injury in guinea pigs. This cardioprotection requires adenosine A1 receptor signaling at the time of ischemia.

Original languageEnglish (US)
Pages (from-to)H2091-H2097
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number5 46-5
DOIs
StatePublished - Nov 1999
Externally publishedYes

Keywords

  • Adenosine
  • Guinea pig
  • Heart

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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