Inhibition of glycolysis or increased perfusate H⁺ buffering capacity, but not their combination, attenuates myocardial stunning

Objective: Both inhibition of glycolysis and enhancement of the H⁺ buffering capacity of the perfusate during ischaemia reduce myocardial reperfusion injury. The aim of the study was to investigate whether these manoeuvres, performed separately or together, could reduce myocardial stunning after brief global ischaemia. Methods: The hearts of male Sprague-Dawley rats were preperfused for 10 min with oxygenated or hypoxic buffer (pH 7.4) containing 100 mM sucrose, 100 mM HEPES, or 5 mM 2-deoxyglucose plus 100 mM sucrose, followed by 15 min of total ischaemia and 30 min of reperfusion. In some hearts, 5 mM 2-deoxyglucose was combined with 100 mM HEPES during the 10 min preperfusion period. Results: Brief hypoxic preperfusion, 2-deoxyglucose, or HEPES reduced myocardial stunning as well as improving the metabolic recovery and reducing Ca²⁺ overload after reperfusion. These changes were associated with a smaller increase in intracellular Na⁺ and a smaller decrease of coronary effluent pH at the end of ischaemia. In contrast, the combination of HEPES with hypoxic preperfusion or 2-deoxyglucose depressed functional recovery and increased the intracellular Na⁺ level at the end of ischaemia as well as increasing Ca²⁺ overload after reperfusion. This happened even though the decrease in coronary effluent pH was attenuated to the same extent as before. Conclusions: Both inhibition of glycolysis and enhancement of the perfusate H⁺ buffering capacity before ischaemia attenuated myocardial stunning, but the protective effect of each manoeuvre was lost when they were combined.