Effects of graded perfusion and isovolumic work on epicardial and venous adenosine and cytosolic metabolism.

Epicardial adenosine levels and venous adenosine release were measured in isovolumically contracting (ISO) and empty non-isovolumic (non-ISO) guinea-pig hearts subjected to graded perfusion (approximately 7.5, 5.5, 4.0, 2.0, and 1.0 ml/min/g). Myocardial metabolism was monitored using 31P-NMR spectroscopy. At flows of 5.5 ml/min/g or higher epicardial adenosine levels were stable and comparable in ISO and non-ISO hearts (approximately 160 nM). At flows of 4.0 ml/min/g or higher venous adenosine release was stable and comparable in ISO and non-ISO hearts (approximately 30 pmol/min/g). At lower flows, epicardial adenosine and venous adenosine release both increased and were significantly higher in ISO hearts, compared to non-ISO hearts, at each flow rate. Whereas epicardial adenosine increased linearly in ISO and non-ISO hearts at low flows, venous adenosine release stabilized in ISO hearts perfused at 1.0 ml/min/g. Epicardial adenosine, venous adenosine release, and log [ATP]/[ADP] [Pi] all displayed significant correlations with the O2 supply:demand ratio which were comparable in ISO and non-ISO hearts. Elevated levels of epicardial adenosine were linearly related to log [ATP]/[ADP] [Pi] and cytosolic [AMP] and these relationships were comparable in ISO and non-ISO hearts. Alternatively, changes in venous adenosine release did not display simple relationships with log [ATP]/[ADP] [Pi] and cytosolic [AMP] and they were not comparable in ISO and non-ISO hearts. The data indicate that: (i) myocardial adenosine formation increases only below a metabolic threshold corresponding to log [ATP]/[ADP] [Pi] = 5.0 and O2 supply:demand = 1.5 in ISO and non-ISO guinea-pig hearts; (ii) stimulated epicardial adenosine levels appear to be consistently related to changes in cytosolic metabolism below this threshold in ISO and non-ISO hearts; (iii) more complex relationships exist between venous adenosine release and myocardial metabolism during graded perfusion, possibly reflecting the variety of factors modulating venous adenosine release.