Improved functional recovery of ischemic myocardium by suppression of adenosine catabolism.
Isolated working rat heart preparations were used to ascertain whether the addition of adenosine and prevention of its catabolism could aid in the functional recovery of hearts following global ischemia. Hearts were infused with either 80 micro M EHNA (an adenosine deaminase inhibitor) or 20 micro M adenosine and EHNA in either normal (2.4 mM) or low (0.05 mM) calcium-containing buffer prior to clamping of the aorta for 30 minutes. In one series of hearts, postischemic concentrations (mumoles/gram wet weight) of adenosine triphosphate (ATP), diphosphate (ADP), and monophosphate (AMP), adenosine, inosine, and hypoxanthine were measured; in another series, the recovery of aortic flow rate was used as a measure of functional recovery of ventricular muscle. With normal electrolyte balance, EHNA was unable to protect hearts against ATP loss and ventricular failure. Hearts with EHNA + adenosine recovered 14% of preischemic aortic output and ATP levels were slightly elevated at 0.93 mumole/gm. Those treated with either EHNA or EHNA + adenosine in low-calcium buffer recoverd 100% of their original aortic output. However, EHNA + adenosine maintained considerably higher ATP levels (1.57 mumoles/gm) than did EHNA alone (1.14 mumoles/gm) and was associated with faster initial recovery of aortic output. Thus the prevention of adenosine catabolism was insufficient for adequate ventricular recovery unless the tissue ATP was maintained above about 1.0 mumole/gm. EHNA + adenosine in a 0.05 mM Ca++ infusion solution conserved ATP, markedly improved the functional recovery of hearts, and thus may have a role to play in myocardial preservation during elective cardiac arrest.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000008:administration & dosage; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000249:Adenosine Monophosphate; C010192:9-(2-hydroxy-3-nonyl)adenine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000225:Adenine; D000241:Adenosine; D002118:Calcium