The beneficial effects of
pyruvate in organ
reperfusion injury have been documented, however the
therapeutic use of
pyruvate has been hindered by the lack of an appropriate delivery method.
Pyruvic acid is unstable and high rates of
sodium pyruvate infusion are toxic.
Dipyruvyl-acetyl-glycerol (DPAG)
ester was developed as a novel method for intravenous
pyruvate delivery at a high rate without
sodium overload. We tested the ability of DPAG to reduce
myocardial infarct size when administered after severe
myocardial ischemia in an anesthetized open-chest pig model of
ischemia-reperfusion injury.
Ischemia was induced by total occlusion of the distal 2/3 of the left anterior descending coronary artery for one hour, followed by two hours of reperfusion. Animals were either untreated (n = 7), or treated with intravenous DPAG (8.0 mg/kg(-1). min(-1), n = 8) during the two hours of reperfusion.
Infarct size was measured on blinded samples using tetrazolium staining. The DPAG treated group had elevated
pyruvate levels (0.82 +/- 0.07 mM) and reduced
infarct size (20.1 +/- 4.2% of the volume at risk, compared to 30.8 +/- 4.6% in the untreated animals (p < 0.05)), with no difference in blood pressure or heart rate between groups. In conclusion, an
intravenous infusion of DPAG safely increases arterial
pyruvate concentration and reduces
myocardial infarct size following
myocardial ischemia.