Role of adenosine in coronary autoregulation

Abstract

The role of cardiac interstitial adenosine as an important metabolite in coronary autoregulation has not been established. We therefore measured steady-state cardiac interstitial adenosine concentration at a high and a low coronary inflow pressure using an epicardial diffusion well in anesthetized dogs. Although coronary resistance for the high and low pressure points showed highly significant differences (P less than 0.001), adenosine averaged 302 +/- 98 and 286 +/- 91 (SD) pmol/ml for the high and low pressure points, respectively (P greater than 0.20). Cardiac interstitial adenosine concentration was then measured with and without an intracoronary infusion of adenosine deaminase catalytic subunit. Adenosine averaged 28 +/- 21 (SD) pmol/ml during the infusion compared with 281 +/- 68 during control conditions (P less than 0.001). Finally, pressure-flow relations were obtained with and without the adenosine deaminase infusion, and there was no loss of autoregulation in the pressure of adenosine deaminase. These findings indicate that intracoronary adenosine deaminase markedly reduces interstitial adenosine concentration, that cardiac interstitial adenosine concentration remains constant during autoregulation, and that the coronary bed autoregulates normally when interstitial adenosine is reduced to levels close to zero. We conclude that cardiac interstitial adenosine concentration is not an important component in coronary autoregulation.

Role of K+ ATP channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow.

“…Previous studies have demonstrated that endogenous adenosine is not obligatory for maintaining coronary blood flow during normal arterial inflow. Thus, studies in anesthetized open-chest dogs (15)(16)(17)(18)(19) and awake dogs (1,20) failed to demonstrate an effect of intracoronary adenosine deaminase (15)(16)(17), or adenosine receptor blockade with intravenous aminophylline (18, 19) or 8-phenyltheophylline (1, 20), on (21) examined the effect of exercise on myocardial adenosine production. They found that treadmill exercise in dogs resulted in a fivefold increase in myocardial adenosine content, with a doubling of the coronary arterio-venous adenosine content difference.…”

Endogenous adenosine mediates coronary vasodilation during exercise after K(ATP)+ channel blockade.

“…Previous studies have demonstrated that endogenous adenosine production is not obligatory for maintaining resting CBF. Thus, studies in anesthetized openchest dogs failed to demonstrate an effect of intracoronary adenosine deaminase (18)(19)(20) or intravenous aminophylline to block adenosine receptors (21,22), on basal CBF. Similarly, in awake dogs intracoronary adenosine deaminase or intravenous 8-phenyltheophylline, in doses that caused marked inhibition of exogenous adenosine-induced coronary vasodilation, had no effect on resting CBF (1,23 gated the role of KAT channels in maintaining resting CBF.…”

Autoregulation of blood flow.

“…On the other hand, Dole et al 37 found that adenosine deaminase infused into the blood-perfused dog myocardium moderately reduced the magnitude of reactive hyperemia but did not significantly affect autoregulation. Hanley et al 38 also found that adenosine deaminase did not attenuate autoregulation the blood-perfused dog heart. Winn and co-workers 39 found adenosine levels in the rat brain increased as systemic arterial pressure was reduced, but the increase was statistically significant only at pressures below the autoregulatory range.…”