Adenosine and the stunned heart.
Adenosine is one agent under investigation as a therapeutic intervention of myocardial stunning. Adenosine caused numerous effects on the cardiovascular system through its interaction with A1 and A2 receptors. We investigated adenosine A1 receptor mediated mechanisms of cardiac protection in the stunned rat myocardium. Previous studies showed that both adenosine and R-phenylisopropyladenosine (PIA), an A1 receptor agonist, prolonged the time to onset of ischemic contracture in ischemic isolated rat hearts. Phenylaminoadenosine, an A2 receptor agonist, did not have any effect, while receptor antagonists blocked adenosine and PIA action. Direct attenuation of the effects of myocardial stunning was observed by altering levels of interstitial fluid adenosine. Our laboratory has shown that administration of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA; an adenosine deaminase inhibitor) to dogs subjected to left anterior descending coronary artery (LAD) occlusion followed by reperfusion results in dramatic increases in ischemic levels of interstitial fluid adenosine and postischemic myocardial function. Using a similar model in dogs, we have shown that exogenous intracoronary adenosine (50 micrograms/kg per min) augmented postischemic recovery of function, as assessed by significant enhancement (p < 0.01) of systolic wall thickness (7.0 +/- 3.0 pretreatment vs -5.7 +/- 1.7 controls). These data support the role for an adenosine A1 receptor mediated mechanism for protection against myocardial stunning.
Randhawa
M P
MP
Division of Cardiothoracic Surgery, University of Wisconsin Hospitals, Madison 53792.
Lasley
R D
RD
Mentzer
R M
RM
D000241:Adenosine / Q000502:physiology / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D011983:Receptors, Purinergic / Q000187:drug effects
D011983:Receptors, Purinergic; D000241:Adenosine