Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia

Abstract

Objective Myocardial injury and dysfunction following ischemia are mediated in part by reactive oxygen species. Pyruvate, a key glycolytic intermediary, is an effective free radical scavenger but unfortunately is limited by aqueous instability. The ester derivative, ethyl pyruvate, is stable in solution and should function as an antioxidant and energy precursor. This study sought to evaluate ethyl pyruvate as a myocardial protective agent in a rat model of ischemia-reperfusion injury. Methods Rats underwent 30-minute ischemia and 30-minute reperfusion of the left anterior descending coronary artery territory. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of either ethyl pyruvate (n = 26) or vehicle control (n = 26). Myocardial high-energy phosphate levels were determined by adenosine triphosphate assay, oxidative injury was measured by lipid peroxidation assay, infarct size was quantified by triphenyltetrazolium chloride staining, and cardiac function was assessed in vivo. Results Ethyl pyruvate administration significantly increased myocardial adenosine triphosphate levels compared with control (87.6 ± 29.2 nmol/g vs 10.0 ± 2.4 nmol/g, P = .03). In ischemic myocardium, ethyl pyruvate reduced oxidative injury compared with control (63.8 ± 3.3 nmol/g vs 89.5 ± 3.0 nmol/g, P < .001). Ethyl pyruvate diminished infarct size as a percentage of area at risk (25.3% ± 1.5% vs 33.6% ± 2.1%, P = .005). Ethyl pyruvate improved myocardial function compared with control (maximum pressure: 86.6 ± 2.9 mm Hg vs 73.5 ± 2.5 mm Hg, P < .001; maximum rate of pressure rise: 3518 ± 243 mm Hg/s vs 2703 ± 175 mm Hg/s, P = .005; maximal rate of ventricular systolic volume ejection: 3097 ± 479 μL/s vs 2120 ± 287 μL/s, P = .04; ejection fraction: 41.9% ± 3.8% vs 31.4% ± 4.1%, P = .03; cardiac output: 26.7 ± 0.9 mL/min vs 22.7 ± 1.3 mL/min, P = .01; and end-systolic pressure-volume relationship slope: 1.09 ± 0.22 vs 0.59 ± 0.2, P = .02). Conclusions In this study of myocardial ischemia-reperfusion injury, ethyl pyruvate enhanced myocardial adenosine triphosphate levels, attenuated myocardial oxidative injury, decreased infarct size, and preserved cardiac function.