Sensitivity of mechanical and metabolic functions to changes in coronary perfusion: A metabolic basis of perfusion-contraction coupling

Experimental evidence indicates a metabolic basis of contraction-perfusion coupling during an increase in cardiac work load. This study aims to charac terize adjustment of myocardial energy metabolism in response to acute low flow ischemia (LFI), and to determine its involvement in perfusion-contract ion coupling. Intracellular parameters were measured in isolated rat hearts by NMR spectroscopy and biochemical methods during 30 min of graded LFI an d reperfusion as compared tc, continuous perfusion (control). Oxygen pressu re was set to reach maximal oxygen extraction at 70% coronary flow rate (CF R), therefore oxygen limitation was proportional to coronary underperfusion , At 69, 38 and 10% CFR left ventricular pressures decreased to 71, 43 and 25% of pre-ischemic Values respectively (P<0.005 v 97% in control) without an increase in diastolic tone, and recovered to 92 +/- 3% after 30 min of r eperfusion. Despite hydrolysis of high energy phosphates and cellular acidi fication, ADP concentrations were stable in underperfused hearts. At 69, 38 and 10% CFR, cytosolic phosphorylation potentials (Pr) decreased from 74 /- 10 mM(-1) during pre-ischemia to 40 +/- 6, 25 +/- 4 and 14 +/- 4 mM(-1) respectively (P<0.05 v 63 +/- 9 mM(-1) in control), and lactate efflux incr eased to 256 +/- 18, 386 +/- 22 and 490 +/- 43 mu mol/gdw respectively (P<0 .005 v 186 +/- 22 mu mol/gdw in control). Glycogen contents decreased (P<0. 005 v control) and accounted for 27-30% of lactate efflux, These results in dicate: (a) proportionate depression of contraction force and glycogen cont ents, and increased glucose uptake and anaerobic energy production in the u nderperfused myocardium. Coordinated modulation of these parameters attribu tes cytosolic PP a regulatory function; (b) resetting of cytosolic PP to lo wer levels mediates perfusion-contraction coupling during graded LFI. The d ata are consistent with the concept that glycolytic energy production impro ves myocardial tolerance to ischemia, (C) 2000 Academic Press.