The local control of coronary blood flow

The mechanism of local metabolic regulation of coronary blood flow is still unclear. It is still unknown which control system- an "open-loop feedback control" or a "close-loop control" - operates in the coronary circulation and whether common mechanisms exist in this control. To separate the putative chemicals proposed to be physiological regulators in the coronary bed, the time courses of coronary resistance change in response to either increased cardiac work or hypoxia have been examined, before and after a, ß and adenosine inhibition. An acute open-chest sheep model was used for this investigation. The sheep were anaesthetised with sodium pentobarbitone and instrumented for circumflex coronary artery and pulmonary artery flows, left ventricular, proximal aortic and coronary sinus pressure. Continuous coronary sinus oxygen saturation was measured by a fibre optic technique. Blood samples from coronary sinus and proximal aorta were analysed for blood gases, Na+ and K+. An occluding band was placed around the proximal aorta to produce variable increments of aortic pressure for variable periods. Low oxygen gases (5%02, 5%C02 and 90%N2) were used to produce systemic hypoxia. Phentolamine, propranalol and 8-phenyltheophylline were used as a, ß and adenosine blockers respectively, and nonadrenaline and isoprenaline (injected into left ventricle) and intra-coronary injection of adenosine were used to test the efficacy of the blockers. Continuous coronary resistance was calculated throughout each intervention. The recovery of coronary resistance to normal after the change of the afterload of the left ventricle had a constant half life of 4.7±0.2 seconds. The half life was not related to either the degree or the duration of increased work. a, ß and adenosine inhibitors did not alter the half life, but produced more profound changes in coronary resistance due to increased cardiac work. The half life of exogenous adenosine was about 26 seconds. During the increase of aortic pressure the coronary sinus oxygen saturation varied significantly both above and below the steady state unpredictably, but with systemic hypoxia there was vasodilation during which the oxygen level in the coronary sinus was closely linked to coronary resistance with a small "hysteresis" when the hypoxia was reversed. After adenosine blockade, the coronary resistance and oxygen supply were more closer linked. The results suggest an open loop control system with a short acting mediator whose half life is the same for varying periods and degrees of increased work, but very much shorter than that of adenosine. The metabolic control of coronary flow is not dependent on the oxygen requirements of the muscle. Multiple factors may involved in the local coronary vasoregulation. Current data do not support adenosine as the common factor in metabolic vasodilation