Background: Acute myocardial ischemia results in an increase in extracellular K
+ ([K
+]
e) and a decrease in extracellular pH (pH
e). We examined the effects of these changes on conduction and the effective refractory period (ERP) during acute myocardial ischemia. Methods: We inserted K
+- sensitive electrodes into the mid-myocardium and bipolar plunge electrodes into the subendocardium and subepicardium of in-situ canine hearts. A unipolar electrode was inserted into the mid-myocardium. The carotid artery was shunted to the LAD through a roller pump, and KCl was infused into the side arm of the shunt. Systematic metabolic acidosis (MA) and respiratory acidosis (RA) were induced in 10 animals each by infusion of NH
4Cl and inhalation of CO2, respectively. Results: Under regional hyperkalemia (([K
+]
e = 10.23 ± 1.15 mM in the MA group and 9.28 ± 1.19 mM in the RA group), the intramyocardial conduction time (CT) increased by 20%. The CT did not change under RA or MA alone. When regional hyperkalemia plus MA ([K
+]
e = 8.94 ± 1.87, pH = 7.06 ± 0.06) or RA ([K
+]
e = 9.33 ± 0.63, pH = 6.75 ± 0.20) were both induced, the CT increased further by 50% compared to the control/baseline state. The ERP did not change significantly with regional hyperkalemia or regional hyperkalemia plus RA or MA. Conclusion: Our data indicate that the fall in pHe that results from myocardial ischemia enhances the conduction slowing induced by the rise in [K
+]
e.
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