Effect of adenosine on contractile state and oxygen consumption in isolated rat hearts.
We studied the effects of adenosine on oxygen consumption and contractile state in 17 isolated, crystalloid-perfused, isovolumically contracting rat heart preparations at constant coronary flow. In 10 experiments we determined adenosine-contractile state dose-response relationships in three groups of hearts using two different perfusates and in the presence and absence of adrenergic blockade. Adenosine consistently reduced contractile state in a dose-dependent fashion, reducing the ventricular pressure developed at a constant ventricular volume by 24% on average at its maximal effect. An adenosine concentration of 111 microM on average produced 50% of the maximal effect. In seven experiments we determined the end-systolic pressure-volume and oxygen consumption-pressure-volume area (MVO2-PVA) relationships at two calcium concentrations (1.5 and 0.75 mM) and with adenosine 400 microM (1.5 mM Ca2+). Contractile state was indexed by the developed pressure at a ventricular volume of 0.3 ml (P0.3). Compared with 1.5 mM Ca2+, mean P0.3 was reduced by 38% with 0.75 mM Ca2+ and by 18% with adenosine. Whereas the MVO2-PVA slopes did not change, the mean MVO2 intercept was reduced by 22% with 0.75 mM Ca2+ and by 13% with adenosine. The MVO2 intercept, which represents the oxygen consumed by the unloaded heart, was directly related to P0.3. This relationship, which represents the oxygen cost of contractility, was not affected by adenosine. We conclude that at constant coronary flow and perfusion pressure adenosine reduces myocardial contractility and the oxygen consumed for excitation-contraction coupling. However, adenosine does not affect the slope of the MVO2-PVA relation or the oxygen cost of contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
Wannenburg
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Section on Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1045.
de Tombe
P P
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Little
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WC
D000241:Adenosine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole / Q000187:drug effects / Q000502:physiology
D000241:Adenosine; D002118:Calcium