Effective myocardial protection during cardiac surgery is essential, yet the differential metabolic stress of the left (LV) and right ventricles (RV) to ischemia–reperfusion remains poorly characterized.

This predefined substudy of a multicenter randomized trial conducted in the United Kingdom (ISRCTN33084113) evaluated remote ischemic preconditioning in patients undergoing coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). Paired LV and RV biopsies were obtained before ischemia and after reperfusion. High-performance liquid chromatography was used to quantify metabolite concentrations and calculate markers of energetics. Cross-clamp time and postoperative troponin levels were recorded.

Eighty-nine patients were included (CABG: n = 49; AVR: n = 40). Following ischemia–reperfusion, LV exhibited greater decline in metabolites than the RV. In CABG, this included larger sustained fall in ATP (−0.90 vs −0.13 μmol/mg, p = 0.0032) and glutamate (−4.22 vs −1.33 μmol/mg, p = 0.0009), alongside ADP (−0.53 vs −0.20 μmol/mg, p = 0.0196), GTP (−0.04 vs −0.01 μmol/mg, p = 0.0160), and B-NAD (−0.15 vs −0.04 μmol/mg, p = 0.0137). Computed energy charge decreased significantly in both ventricles (LV: p = 0.0002; RV: p = 0.010), but remained stable in AVR. ATP/AMP and ATP/ADP ratios declined more in the LV, suggesting impaired energy buffering. There was no significant correlation between cross-clamp time and changes in energy charge in either the LV or RV. Troponin release correlated with ischemic time in CABG, but EC decline did not.

The LV shows greater depletion of myocardial metabolites than the RV following ischemia–reperfusion, particularly in CABG patients. These findings support ventricle-specific strategies to optimize myocardial protection.