Coronary Artery Disease: Regulation of Coronary Blood Flow

Abstract

Over a wide range of activity, coronary blood fl ow is closely matched to myocardial metabolic requirements to maintain a consistently high level of oxygen extraction by the heart. Even during resting conditions 70% to 80% of the oxygen perfusing the coronary capillaries is extracted by the myocar-dium, so there is little ability to increase oxygen uptake by means of increasing oxygen extraction. 1 For this reason, increases of oxygen demands during exercise or other stress must be met by proportionate increases in coronary fl ow. Close coupling of coronary blood fl ow to cardiac work is further mandated by the strongly oxidative nature of energy production by the heart. More than 95% of the adenosine tri-phosphate (ATP) utilized by the myocardium is produced through oxidative phosphorylation, which requires a continuous supply of oxygen to the mitochondria. 2 Since the ATP pool of the heart turns over four to fi ve times per minute, failure of ATP production to equal ATP consumption results in loss of contractile function within a few seconds. Reductions of coronary blood fl ow by as little as 10% to 20% result in contractile dysfunction and depletion of high-energy phosphates. 3,4 These considerations imply that the myocardium functions near the brink of ischemia, and emphasizes the importance of the mechanisms by which coronary vasomotor tone is adjusted in response to beat-to-beat changes of myocardial energy demands. Ischemia occurs when diseased coronary vessels are unable to deliver suffi cient arterial infl ow to meet myocar-dial metabolic demands. When coronary fl ow is limited by an arterial stenosis, myocardial oxygen demands play a decisive role in setting the threshold for ischemia.