DISSOCIATION BETWEEN ADENOSINE RELEASE, MV(O2), AND ENERGY STATUS IN WORKING GUINEA-PIG HEARTS

Rapid adaptation of ATP formation and coronary flow is required when c ardiac work is altered. Cardiac energy status was proposed to control both oxygen consumption (MV over dot O-2) and release of vasoactive ad enosine (AR). To investigate the hypothesis of a linear relation betwe en free AMP and AR, we employed P-31 nuclear magnetic resonance (NMR) in a newly elaborated guinea pig heart performing pressure-volume work . Under basal conditions, MV over dot O-2 was 7.8 +/- 1.0 mu mol . min (-1). g(-1), free AMP 297 +/- 189 nM and AR 226 +/- 179 pmol . min(-1) . g(-1) (n = 29). Decreasing arterial Po-2 by 50% reduced MV over dot O-2 and increased free AMP by 29%; however, AR rose threefold (n = 5). Doubling oxygen content of the perfusion medium (fluorocarbon emulsio n) did not alter MV over dot O-2, free AMP, or AR (n = 6). When afterl oad was doubled, MV over dot O-2 increased (+45%) and AR decreased (-6 0%) despite no change in ADP or AMP (n = 6). Dobutamine increased MV o ver dot O-2, (+50%) and AMP (+98%); however, AR rose more than five ti mes (n = 8). Switching substrates from glucose + pyruvate to glucose d iminished MV over dot O-2 and increased ADP twofold and AMP fourfold, whereas AR remained constant (n = 6). Our findings demonstrate that ca rdiac energy status is also not the prime regulator of oxidative phosp horylation in the isolated heart. Changes in the oxygen supply-to-dema nd ratio induced a rise in AR that exceeded by far the increase in fre e AMP. Thus, additional factors, possibly inhibition of adenosine kina se, influence the release of vasoactive adenosine.