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The ionic basis of ventricular arrhythmias induced by a cardiac glycoside was studied in pentobarbital-anesthetized dogs. The effects of ouabain alone and in combination with hypothermia or pronethalol on myocardial and plasma Na+ and K+ were determined. Hypothermia (26°C) and pronethalol (15 mg/kg, iv) had similar effects on the standard lead II of the EGG, i.e., a decrease in heart rate and increases in P-R, QRS, and Q-T intervals. In the absence of ouabain, hypothermia and pronethalol each produced small and inconsistent changes in intracellular Na+ and K+ concentrations. Both hypothermia and pronethalol were found to significantly increase the threshold toxic dose of ouabain required to produce a ventricular arrhythmia within the test period of 90 minutes. Both pronethalol and hypothermia effectively prevented ouabaininduced changes in myocardial Na+ and K+ when arrhythmias were prevented. When sufficient ouabain was given to produce an arrhythmia, there was always a significant fall inmyocardial K+. In unprotected and in hypothermic animals, these arrhythmias were also associated with a significant increase in left ventricular Na +. The effect of ouabain on Na+ was not significant in pronethalol-treated dogs.

Effects of Hypothermia and Pronethalol on Ionic Correlates of Ouabain Arrhythmias in Dogs