Ischemic Preconditioning Prior to Aortic Cross-Clamping Protects High-Energy Phosphate Levels, Glucose Uptake, and Myocyte Contractility

Abstract

Background. We hypothesized that indices of myocyte contractility and metabolism could be preserved with ischemic preconditioning in a model of reversible ischemia similar to that occurring during routine cardiac surgery. Regional measures of metabolism and function have not been studied in conjunction with individual myocyte function during postischemic recovery of preconditioned myocardium.Patients and methods. In 16 dogs, myocardium supplied by the left anterior descending artery (LAD) was preconditioned with intermittent LAD ischemia and reperfusion. Following preconditioning, the heart was made globally ischemic for 20 min at normothermia by aortic cross-clamping while on cardiopulmonary bypass. In 10 animals, serial measurements of LAD and remote region adenosine triphosphate (ATP) levels, glucose uptake, and wall thickening were obtained with full-thickness drill biopsies, positron emission tomography (PET), and 2-D echocardiography, respectively. In the remaining 6 animals, cardiac myocytes were isolated after 1 h of reperfusion for measurement of myocyte contractility and intracellular calcium transients.Results. ATP levels were higher in the preconditioned LAD region than in the remote region at end of ischemia (3.17 ± 0.33 nmol/mg vs 2.59 ± 0.30 nmol/mg, P = 0.006). Similarly, preconditioned region glucose uptake was 40% higher than remote region glucose uptake at 2 days postischemia (0.35 ± 0.06 μmol/min/g vs 0.25 ± 0.05 μmol/min/g, P = 0.019). There were no differences in regional wall thickening as measured by 2-D echo either immediately following ischemia or at 2 days. Individual myocyte contractile response to increasing concentrations of extracellular calcium was preserved in cells from preconditioned myocardium, but it was severely depressed in remote region myocytes.Conclusions. We conclude that regional ischemic preconditioning prior to prolonged ischemia protects myocardial glucose uptake and myocyte contractile function. The beneficial effects on glucose metabolism suggest that preconditioning may have sustained protective effects on cell metabolism.