Effects of pyruvate on the energetics of rat ventricles stunned by ischemia-reperfusion

Pyruvate (Pyr) was proposed as an additive to cold high-K+-low-Ca2+ cardioplegia (CPG) to protect the heart during surgery. We explored whether Pyr and CPG would work synergistically to protect rat hearts from stunning during ischemia-reperfusion (I/R). We measured the heat release and contractility of perfused ventricles during I/R, and the cytosolic and mitochondrial [Ca2+] in cardiomyocytes by confocal microscopy. We found that under cold-CPG (30 degrees C), 10 mmol.L-1 Pyr reduced the post-ischemic contractile recovery (PICR) as well as muscle economy, when added either before ischemia or during I/R, which was reversed by blockade of UCam. In noncardioplegic hearts, Pyr was cardioprotective when it was present during I/R, more so at 37 degrees C than at 30 degrees C, with improved economy. In cardiomyocytes, the addition of Pyr to CPG slightly increased the mitochondrial [Ca2+] but decreased cytosolic [Ca2+]. The results suggest that Pyr only protects hearts from stunning when present before ischemia and during reperfusion, and that it dampens the cardioprotective properties of CPG. The mechanisms underlying such different behavior depend on the dynamic balance between Pyr stimulation of the energetic state and mitochondrial Ca2+ uptake. Our results support the use of Pyr in stunned hearts, but not in cold high-K+ cardioplegia.