Adenosine increases lactate release and delays onset of contracture during global low flow ischaemia.
OBJECTIVE
Adenosine reduces myocardial ischaemic injury and enhances postischaemic recovery of function following zero flow global and regional ischaemia. The purpose of this study was to determine the functional and metabolic effects of endogenous and exogenous adenosine during low flow ischaemia.


METHODS
Isolated perfused rat hearts (n = 80), paced at 300 beats-min-1, were subjected to 45 min of low flow ischaemia (0.6 ml.min-1). The time to onset of ischaemic contracture (TOIC) was used as a marker of myocardial ischaemic injury. Coronary venous effluent samples were collected prior to and throughout ischaemia to measure lactate and purine release. Untreated hearts were compared to hearts treated with either adenosine (100 microM), adenosine plus EHNA (erythro-9-[2-hydroxy-3-nonyl]adenine HCl), an adenosine deaminase inhibitor (50 microM), or BW A1433U, an adenosine receptor blocker (5 microM).


RESULTS
Adenosine and adenosine+EHNA prolonged TOIC from 11.6 (SEM 0.5) min to 13.6(0.5) and 13.5(0.3) min, respectively, and increased lactate release from 1.67(0.19) mumol.min-1.g-1 to 2.20(0.09) and 2.35(0.31) mumol.min-1.g-1, respectively, after 20 min ischaemia. Treatment with BW A1433U reduced TOIC [8.7(0.2)min] and markedly reduced lactate release. When glucose was omitted from the perfusate, adenosine+EHNA treatment had no effect on TOIC. Lactate release during glucose free perfusion was similar to that in hearts treated with the adenosine receptor blocker.


CONCLUSIONS
Endogenous and exogenous adenosine may enhance myocardial tolerance to ischaemia in part via the modulation of glucose metabolism.
Lasley
R D
RD
Department of Surgery, University of Wisconsin, Madison 53792.
Mentzer
R M
RM
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007773:Lactates / Q000096:biosynthesis*; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000494:pharmacology
D007773:Lactates; D014970:Xanthines; D019344:Lactic Acid; C010192:9-(2-hydroxy-3-nonyl)adenine; C053414:BW A1433U; D005947:Glucose; D000225:Adenine; D000241:Adenosine