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

¹ Department of Pharmacology, University California Medical Center San Francisco, California 94122

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.

Accepted on October 29, 1968