Coronary metabolic control

Metabolic control of coronary blood flow R.M. Berne... 

Thromboxane A-2 has been implicated in a number of disorders of the circulatory system including coronary artery spasms, unstable angina pectoris, traumatic and endotoxic shock, and heart attacks. It is formed normally very near its receptors and is rapidly deactivated by metabolizing enzymes so circulating levels are quite low. Furthermore, it is opposed in its actions by the prostacyclins. When these controls are defective, pathology results and drugs can be the resort in attempts to restore the normal healthy balance. For one example, furegrelate (6) is a throm-... 

The effects of coenzyme Q10 on coronary artery disease and chronic stable angina are modest but appear promising. A theoretical basis for such benefit could be metabolic protection of the ischemic myocardium. Double-blind, placebo-controlled trials have demonstrated that coenzyme Q10 supplementation improved a number of clinical measures in patients with a history of acute myocardial infarction (AMI). Improvements have been observed in lipoprotein a, high-density lipoprotein cholesterol, exercise tolerance, and time to development of ischemic changes on the electrocardiogram during stress tests. In addition, very small reductions in cardiac deaths and rate of reinfarction in patients with previous AMI have been reported (absolute risk reduction 1.5%). 

The caliber of arteriolar resistance vessels controls blood flow through the coronary bed. Arteriolar caliber is determined by myocardial 02 tension and local concentrations of metabolic products, and is automatically adjusted to the required blood flow (B, healthy subject). This metabolic autoregulation explains why anginal attacks in coronary sclerosis occur only during exercise (B, patient). At rest, the pathologically elevated flow resistance is... 

Reaven (1988) suggested that insulin resistance might be a common denominator for obesity, Type-II diabetes hypertension and hyperlipidaemia (metabolic syndrome) and should be treated rigorously to avoid coronary heart disease, the most common cause of morbidity and mortality in Type-II diabetes mellitus. However, it still remains to be proven that effective blood glucose control will reduce the mortality of the disease (Turner and Holman, 1990). 

Myogenic control (also known as the Bayliss effect) of coronary artery tone occurs when the vessel is stretched secondary to an increase in pressure and contracts to return blood flow to normal. It is thought that the myogenic response to stretching in coronary arteries is a modest one and that metabolic factors such as nitric oxide play a much larger role in autoregulation. 

The molecular structure of the smooth muscle Kjr channel is unknown, although, based on its properties, it is likely to be a member of the IRK family. Inward rectifier potassium currents have been identified in small cerebral, coronary (see Fig. 2A), and mesenteric arterioles (<200 i.m diameter). The presence of K[r channels may be a common feature in small arteries that determine in large part peripheral vascular resistance. It is not known if Kjr channels are exclusively present in small arteries, although they have not yet been reported in larger vessels. Innervation of this size artery (<100-200 j.m) is usually sparse and therefore small arteries may be more prone to respond to metabolic demand from the tissue, as reflected by potassium efflux. Thus, the appearance of K,r channels may reflect a transition of blood flow regulation to local (tissue) control. This is an intriguing hypothesis that remains to be tested. It will be important to study systematically the distribution of the K r channel within a vascular bed, as this may have physiological consequences. Kir channels, like K and K jp channels. 

---