Effects of barbiturate anesthetics and ketamine on the force-frequency relation of cardiac muscle.

The effects of ketamine and barbiturates (pentobarbital, thiopental, methohexital) were studied in an isolated rabbit Langendorff preparation. All agents tested depressed contractility. Ketamine, as well as the lipophilic barbiturates (thiopental, methohexital), caused a relatively greater depression at higher pacing rates such that the force-frequency relation was reversed. Pentobarbital did not reverse Bowditch. The effects of barbiturates on Bowditch correlated directly with lipid solubility, suggesting that their rate-related effects are due to perturbation of the membrane lipid bilayer. Disruption of hydrogen bands between polar membrane components may also be involved. The time course of the effect of thipental at high pacing rates was slower, both in onset and recovery, than at low rates. At a pacing rate of 1 Hz, maximal depression of contraction developed within 5 min. However, at 2.5 Hz, contractility continued to decline for up to 30 min. After 5 min of perfusion with thiopental, Bowditch was still positive, but by 30 min it was reversed. These temporal differences in thipental effects suggest that different mechanisms may dominate in the support of contractility at different ranges of heart rate.