Transmural inhomogeneity of extracellular [K⁺] and pH and myocardial energy metabolism in the isolated rat heart during acute global ischemia; dependence on gaseous environment

Summary

We investigated in the isolated rat heart the influence of the gas surrounding the globally ischemic heart on transmural inhomogeneity of energy metabolism, extracellular K⁺ accumulation, and change of extracellular pH. Hearts were made ischemic in 100% N₂ (N₂-ischemia), 100% O₂ (O₂-ischemia) or 100% CO₂ (CO₂-ischemia). We measured: 1) Midmural, subepicardial, and epicardial changes of extracellular [K⁺] and pH during successive 6-min periods of global ischemia, and 2) content of creatinephosphate (CrP) in consecutive tissue sections of 100 μm, from the subepicardium after 10 min of ischemia.

• A) During O₂-ischemia both extracellular [K⁺] and change of pH in the subepicardium are significantly less than in the midmyocardium. During N₂-ischemia only minor differences exist in [K⁺] and pH between the subepicardium and the midmyocardium. During CO₂-ischemia midmural and subepicardial [K⁺] are similar to those during N₂-ischemia. The midmural change of pH resembles that during N₂-ischemia; subepicardial change of pH, however, was slightly larger. Midmural changes in [K⁺] and pH were not influenced by the nature of the surrounding gas.

• B) After 10 min of O₂-ischemia a gradient of tissue content of CrP extends from the epicardium (CrP about 30 μmoles/g dry weight) to a distance of about 1000 μm (CrP 1 μmoles/g dry weight). In N₂-and CO₂-ischemia a CrP gradient is absent; CrP is appreciably less than 1 μmoles/g dry weight at any distances from the epicardium.

• C) We conclude that diffusion of O₂ into the myocardium and of CO₂ from the myocardium affects transmural gradients of [K⁺], pH, and energy metabolism during ischemia. Local availability of O₂ increases the capacity of the ischemic tissue to generate high energy phosphates and mitigates ischemia-induced changes of transsarcolemmal ion gradients.