EFFECT OF ADENOSINE ON CONTRACTILE STATE AND OXYGEN-CONSUMPTION IN ISOLATED RAT HEARTS

We studied the effects of adenosine on oxygen consumption and contract ile state in 17 isolated, crystalloid-perfused, isovolumically contrac ting rat heart preparations at constant coronary flow. In 10 experimen ts we determined adenosine-contractile state dose-response relationshi ps in three groups of hearts using two different perfusates and in the presence and absence of adrenergic blockade. Adenosine consistently r educed contractile state in a dose-dependent fashion, reducing the ven tricular pressure developed at a constant ventricular volume by 24% on average at its maximal effect. An adenosine concentration of 111 mu M on average produced 50% of the maximal effect. In seven experiments w e determined the end-systolic pressure-volume and oxygen consumption-p ressure-volume area (MVO(2)-PVA) relationships at two calcium concentr ations (1.5 and 0.75 mM) and with adenosine 400 mu M (1.5 mM Ca2+). Co ntractile state was indexed by the developed pressure at a ventricular volume of 0.3 mi (P-0.3) Compared with 1.5 mM Ca2+, mean P-0.3 was re duced by 38% with 0.75 mM Ca2+ and by 18% with adenosine. Whereas the MVO(2)-PVA slopes did not change, the mean MVO(2) intercept was reduce d by 22% with 0.75 mM Ca2+ and by 13% with adenosine. The MVO(2) inter cept, which represents the oxygen consumed by the unloaded heart, was directly related to P-0.3 This relationship, which represents the oxyg en cost of contractility, was not affected by adenosine. We conclude t hat at constant coronary flow and perfusion pressure adenosine reduces myocardial contractility and the oxygen consumed for excitation-contr action coupling. However. adenosine does not affect the slope of the M VO(2)-PVA relation or the oxygen cost of contractility. These results suggest that adenosine reduces contractile state by reducing calcium c ycling and that this results in a reduction in the oxygen consumed for excitation-contraction coupling.