Cardiac adenosine production is linked to myocardial pO2.
Experiments were performed on isolated perfused guinea-pig hearts (n = 45) to further evaluate the stimulus that triggers cardiac adenosine production. Stimulation of hearts with isoproterenol (4 nM, 20 min) enhanced left ventricular dP/dtmax, heart rate and myocardial oxygen consumption within 1 min to new steady state values, whereas coronary venous adenosine concentration only transiently increased reaching its maximum between 1 and 3 min of stimulation. Rate of accumulation of S-adenosylhomocysteine (SAH), a measure of the free cytosolic adenosine concentration, was steepest immediately following onset of stimulation and then progressively declined. Similar to adenosine, changes in coronary venous pO2 were phasic and adenosine release and pO2 closely correlated. Norepinephrine (20 nM) which increased myocardial oxygen consumption to a comparable extent as isoproterenol (4 nM) further decreased coronary venous pO2 and increased coronary venous adenosine. When myocardial oxygen supply was systematically varied by changing coronary perfusion pressure from 60 to 90 and 35 cmH2O, respectively, the adenosine release during isoproterenol (2 nM) was markedly enhanced at 35 cmH2O but blunted at 90 cmH2O. Similarly SAH accumulation was greatest at 35 cmH2O and smallest at 90 cmH2O. It is concluded that changing myocardial oxygen consumption is not a sufficient cause to enhance adenosine formation. Myocardial oxygenation as reflected by changes in coronary venous pO2 closely correlates with changes in free cardiac adenosine as evidenced by two independent indices: tissues SAH and coronary venous adenosine concentration. The stimulus triggering cardiac adenosine formation is most likely the imbalance of oxygen supply and oxygen demand.
Deussen
A
A
Zentrum für Physiologie, Heinrich-Heine-Universität, Düsseldorf, FRG.
Schrader
J
J
D000241:Adenosine / Q000096:biosynthesis*; D000818:Animals; D001784:Blood Gas Analysis; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D010313:Partial Pressure; D010477:Perfusion
D000241:Adenosine; D007545:Isoproterenol; D010100:Oxygen