Enhanced interstitial fluid adenosine attenuates myocardial stunning.
Reversible myocardial dysfunction associated with transient ischemia has been termed the stunned myocardium. Because exogenous adenosine has been shown to protect the ischemic myocardium, we hypothesized that augmentation of endogenous adenosine levels would attenuate myocardial stunning. To induce stunning, anesthetized dogs were subjected to 15 minutes of ischemia (left anterior descending artery occlusion) followed by 60 minutes of reperfusion. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 5 mg/kg/hr), an adenosine deaminase inhibitor, was used to augment adenosine levels. The effect of EHNA on interstitial fluid (ISF) adenosine levels, coronary blood flow, and regional systolic wall thickening was compared with that of an untreated group (n = 8). EHNA increased preischemia ISF adenosine levels threefold and was associated with a corresponding increase in coronary blood flow. EHNA administration did not alter preischemia systolic wall thickening. Although ISF adenosine increased fourfold during ischemia in the untreated group, ISF adenosine increased nearly sixtyfold above preischemia values in the EHNA-treated group and remained elevated throughout reperfusion. Postischemic regional function was enhanced significantly in the group treated with EHNA. These data show that adenosine deaminase inhibition increased ISF adenosine levels and attenuated myocardial stunning. Metabolic manipulation of myocardial ISF nucleoside levels may be beneficial in limiting postischemic myocardial dysfunction.
Dorheim
T A
TA
Department of Surgery, University of Wisconsin, Madison 53792.
Hoffman
A
A
Van Wylen
D G
DG
Mentzer
R M
RM
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects
D058892:Adenosine Deaminase Inhibitors; C010192:9-(2-hydroxy-3-nonyl)adenine; D000225:Adenine; D000241:Adenosine