Dissociation between adenosine release, MVO2, and energy status in working guinea pig hearts

Rapid adaptation of ATP formation and coronary flow is required when cardiac work is altered. Cardiac energy status was proposed to control both oxygen consumption (MV over dot O-2) and release of vasoactive adenosine (AR). To investigate the hypothesis of a linear relation between 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 emulsion) did not alter MV over dot O-2, free AMP, or AR (n = 6). When afterload was doubled, MV over dot O-2 increased (+45%) and AR decreased (-60%) despite no change in ADP or AMP (n = 6). Dobutamine increased MV over dot O-2, (+50%) and AMP (+98%); however, AR rose more than five times (n = 8). Switching substrates from glucose + pyruvate to glucose diminished MV over dot O-2 and increased ADP twofold and AMP fourfold, whereas AR remained constant (n = 6). Our findings demonstrate that cardiac energy status is also not the prime regulator of oxidative phosphorylation in the isolated heart. Changes in the oxygen supply-to-demand ratio induced a rise in AR that exceeded by far the increase in free AMP. Thus, additional factors, possibly inhibition of adenosine kinase, influence the release of vasoactive adenosine.