Intramyocardial injections and protection against myocardial ischemia: An attempt to examine the cardioprotective actions of adenosine

Peter Whittaker, Robert A. Kloner, Karin Przyklenk

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25 Scopus citations

Abstract

Background: Although adenosine has ben proposed to be a cardioprotective agent, direct examination of such protection is confounded by its short half- life and hemodynamic effects. We attempted to avoid these problems by injecting adenosine directly into cardiac muscle. Methods and Results: We gave four adenosine injections (each 0.15 mL, 5 mg · mL-1 saline) into the left ventricular wall of rat hearts before a 60-minute occlusion. Although infarcts were smaller in adenosine-treated hearts (29±6%) than in controls (52±5%; P<.05), injection of saline also reduced infarcts in hearts subjected to needle insertion but no fluid injection differed neither from control nor from fluid-treated hearts (38±4%). Adenosine reduced ectopic beats and the incidence of ventricular tachycardia during occlusion. In contrast, saline injection prolonged the duration of arrhythmias. To examine the spatial relationship between protection and the injection site, we gave 18 saline injections (each 0.15 mL) into canine myocardium before a 60- minute occlusion. Infarcts were smaller in saline-treated hearts than in controls (P<.01). Because infarcts in four hearts occupied <3% of the risk region, we concluded that fluid injection did not itself cause appreciable necrosis and speculated that muscle was protected in the vicinity of the injection site. Previous work indicated that muscle can be protected by stretch. We examined this hypothesis by adding gadolinium chloride (a stretch-activated channel blocker) to the saline (0.008 g · mL-1) injection in rat hearts. We again found small infarcts after saline injection (26±5%); however, gadolinium blocked protection (50±7%; P<.03). Conclusions: Although we were only partially successful in documenting adenosine-mediated carioprotection, we found evidence for myocyte protection via a stretch-activated mechanism.

Original languageEnglish
Pages (from-to)2043-2051
Number of pages9
JournalCirculation
Volume93
Issue number11
DOIs
StatePublished - Jun 1 1996

Keywords

  • Adenosine
  • arrhythmia
  • gadolinium
  • myocardial infarction
  • signal transduction

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