Cardiac contractile function during coronary stenosis in dogs: association of adenosine in glycolytic dependence

Abstract

We tested the hypothesis that during critical coronary stenosis, endogenous adenosine alters myocardial glucose utilization to support myocardial contractile function (MCF). Anesthetized mongrel dogs were instrumented to measure hemodynamic variables, regional MCF (sonomicrometry), and substrate uptakes. Critical coronary artery stenosis was established with a screw clamp on the left circumflex coronary artery (LCX). Either 8-phenyltheophylline (3 x 10(-7) mol/min; adenosine-receptor blockade), iodoacetate (1 x 10(-5) mol/min; glycolysis blockade), or vehicle was infused into the LCX and the left anterior descending coronary artery (LAD). Critical coronary stenosis caused small decreases in arterial blood pressure and LCX blood flow, but no significant changes in MCF or other hemodynamics. There was a significant decrease in the O2 supply-to-consumption ratio in the stenotic region and an increased glucose uptake. Infusion of either 8-phenyltheophylline or iodoacetate caused a decrease in MCF in the stenotic LCX region concomitant with a decreased glucose uptake and without further changes in blood flow. This was not seen in the nonstenotic (LAD) region. These data support the hypothesis, indicating that glycolysis is vital for maintaining regional MCF during a decrease in the myocardial O2 supply-to-consumption ratio and that adenosine is important in this regard, independent of its vasoactive properties.