Prevention of ATP catabolism during myocardial ischemia: a preliminary report.
The enhancement of ATP regeneration following global myocardial ischemia in dogs by both ATP catabolic enzyme blockade and precursor infusion was investigated. The breakdown of AMP to adenosine is catalyzed by 5'-nucleotidase and this enzyme was inhibited during the ischemic period with either concanavalin A (Con A, 3 mg/kg) or alpha, beta-methyleneadenosine 5'-diphosphate (AMP-CP, 250 microM). To provide additional ATP precursors, adenine (30 mg/kg) and ribose (25 mg/kg) (A/R) were also infused into the coronary vasculature during ischemia and recovery on cardiopulmonary bypass. Left ventricular myocardial ATP levels in control animals decreased to 52% of preischemic values during aortic cross clamping, but ATP levels in dogs treated with AMP-CP + A/R fell to only 67% of preischemic values (P less than 0.05). During reperfusion, ATP levels in Con A + A/R (3.43 +/- 0.26 mumol/g wet wt) and AMP-CP + A/R (3.77 +/- 0.42) treated animals were higher than values found in control dogs (2.73 +/- 0.16, P less than 0.05). Infusions of A/R alone without enzyme inhibition did not increase ATP regeneration. The adenine nucleotide energy charge ratio was also increased by enzyme blockade with either inhibitor when combined with precursor infusion. On bypass, left ventricular myocardial blood flow (measured by the microsphere technique) was increased by 140% (P less than 0.01) over control values in all groups receiving A/R; therefore, enhanced ATP levels were not merely the result of increased flow. Renal blood flow was not adversely affected by this combination of drugs as has been previously found with adenosine infusion and inhibition of adenosine catabolism.
D000241:Adenosine / Q000096:biosynthesis; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001783:Blood Flow Velocity; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D012079:Renal Circulation
D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D000241:Adenosine