Metabolic coronary flow regulation--current concepts

The concept of metabolic coronary flow control provides a rationale for the close relationship of coronary flow and myocardial metabolic rate of oxygen. The concept is based on the presence of an oxygen (metabolic) sensor coupled functionally to effector mechanisms, which control vascular tone. Four modes of metabolic control models have been proposed. 1) An oxygen sensor located in the wall of coronary vessels coupling to smooth muscle tension. Endothelial prostaglandin production may support this concept. 2) An oxygen sensing mechanism located in the myocardium and changing metabolism in response to changes of local pO(2). Adenosine is a metabolite produced at an accelerated rate when the supply-to-demand relationship for oxygen falls. 3) Sensing of oxygen turnover may be achieved by carbon dioxide production and, potentially, by mitochondrial production of reactive oxygen species. 4) The red blood cell might serve as an oxygen sensor in response to changes of haemoglobin oxygenation. A potential link to vessel relaxation may be red cell ATP release. A large body of experimental evidence supports the notion that K(ATP) channels play a significant role causing smooth muscle hyper-polarization. However, additional yet unknown effector mechanisms must exist, because block of K(ATP) channels does not lead to deterioration of coronary flow control under conditions of exercise. Thus, although several lines of evidence show that metabolic flow regulation is effective during hypoxic conditions,mechanisms mediating normoxic metabolic flow control still await further clarification.