Effect of plasma insulin level on myocardial blood flow and its mechanism of action

Considerable evidence suggests that coronary endothelium regulates myocardi al blood flow and metabolism by elaborating vasoactive substances. The phys iologic signals mediating this process are uncertain. To test the hypothesi s that the process is influenced by physiologic variation in local insulin concentration, we examined the effect of direct intracoronary insulin infus ion on myocardial blood flow and oxidative substrate metabolism in 10 patie nts with coronary heart disease. Ten men (aged 51 to 68 years) who were fas ting received a 60-minute intracoronary infusion of insulin at a rate (10 m U/min) sufficient to raise coronary venous plasma insulin from 12 +/- 4 to 133 +/- 17 mU/ml without increasing the systemic insulin level, Local coron ary hyperinsulinemia increased coronary sinus blood flow in every subject, from 50 +/- 4 to 61 +/- 6 ml/min (p < 0.01), Insulin also increased myocard ial uptake of glucose (from 6 +/- 1 to 17 +/- 6 mmol/min) and lactate (from 8 +/- 2 to 12 +/- 5 mmol/min), resulting in similar to 30% increase in tot al oxidative substrate uptake, but without increasing myocardial oxygen con sumption (7.0 +/- 0.7 vs 7.1 +/- 0.8 ml/min). Thus, physiologic elevation i n the local plasma insulin concentration increases coronary blood flow in t he absence of any increase in myocardial oxygen demand or consumption, sugg esting a primary reduction in coronary tone, while simultaneously restraini ng the oxidation of imported substrates. These observations are consistent with insulin-mediated elaboration of vasoactive and/or paracrine factors wi thin the coronary circulation. (C) 2000 by Excerpta Medico, Inc.