Prevention and treatment of ischemic injury with nucleosides.
Using Langendorff rat hearts, we tested whether 1. adenosine as a cardioplegic agent, and 2. inosine administered during reperfusion could prevent and treat ischemic injury, respectively. For cardioplegic arrest (37 degrees C), buffer supplemented with 20 mM K+ (K), K + 1 mM adenosine (KA), or none (Control, C), was infused for 3 min at 3 ml/min. Arrest time was 260 +/- 16 s (C), 22 +/- 4 s (K) and 10 +/- 2 s (KA, p less than 0.02 vs K). During 20 min total ischemia, resting tension increased only in C, and remained elevated after 20 min reperfusion. In treated hearts resting tension rose somewhat and returned to baseline. Developed tension: heart rate (g/min) after reperfusion was superior with KA:C (3,180 +/- 830), K (4,380 +/- 390), and KA (6,250 +/- 740, p less than 0.05 vs. K.). Our electrophysiological studies suggest that adenosine increases K(+)-permeability and thereby arrests the sinus node. It did not affect high-energy phosphates. We also tested whether inosine could regenerate nucleotides. We perfused hearts with buffer containing glucose +/- pyruvate. After 15 min no-flow, hearts were reperfused for 45 min with 20 microM inosine and 0.5 mM ribose. Adenine nucleotide levels tended to recover better in the purine-treated groups. Inosine decrease the ATP/ADT ratio by 15% (p less than 0.05) and increased the IMP level 2 times (p less than 0.01) whom pyruvate was absent. It increased the effluent adenosine concentration 6 times (p less than 0.005). Inosine administration +/- pyruvate did not affect function recovery, heart rate or coronary flow. Thus adenosine as adjunct to K(+)-cardioplegia shortened arrest time, and was also beneficial for post-ischemic recovery. Inosine given during reperfusion failed to improve heart function. Both treatments hardly affected cardiac adenine nucleotide levels.
De Jong
J W
JW
Cardiochemical Laboratory, Erasmus University Rotterdam, The Netherlands.
Van der Meer
P
P
Owen
P
P
Opie
L H
LH
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007288:Inosine / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats
D000227:Adenine Nucleotides; D011687:Purines; D011773:Pyruvates; D007288:Inosine; D000241:Adenosine