Autoregulation is defined as the intrinsic ability of an organ to maintain constant flow in the face of changing perfusion pressure. The present study evaluated the role of several potential mediators of coronary autoregulation: interstitial adenosine, ATP-sensitive K+ (K+ATP) channels, and myocardial oxygen and carbon dioxide tensions as reflected by coronary venous oxygen and carbon dioxide tensions. The left main coronary artery was cannulated, and blood was perfused at controlled pressures in closed-chest dogs. Interstitial adenosine concentration was estimated from arterial and venous adenosine concentrations with a previously described mathematical model. Autoregulation of coronary blood flow was observed between 100 and 60 mmHg. Glibenclamide, an inhibitor of K+ATP channels, reduced coronary blood flow by 19% at each perfusion pressure, but autoregulation was preserved. After stepwise reductions in coronary pressure to values > or = 70 mmHg, adenosine concentrations did not increase above basal levels. Adenosine concentration was elevated at 60 mmHg, suggesting a role for adenosine at the limit of coronary autoregulation. Adenosine is not required because glibenclamide, an inhibitor of adenosine-mediated vasodilation, did not reduce autoregulation or increase adenosine concentration. Coronary venous oxygen and carbon dioxide tensions were little changed during autoregulation before the inhibition of K+ATP channels and adenosine vasodilation with glibenclamide. However, coronary venous carbon dioxide tension rose progressively with decreasing coronary pressure after glibenclamide. The increase in carbon dioxide indirectly suggests that carbon dioxide-mediated vasodilation compensated for the loss of K+ATP-channel function. In summary, neither K+ATP channels nor adenosine is necessary to maintain coronary flow in the autoregulatory range of coronary arterial pressure from 100 to 60 mmHg.
Role of adenosine in coronary blood flow regulation after reductions in perfusion pressure.
