Analysis of halothane effects on myocardial force-interval relationships at anesthetic concentrations depressing twitches but not tetanic contractions.

BACKGROUND

Tetanic contractions in rat myocardium depend solely on cellular Ca2+ uptake, whereas twitches depend on Ca2+ release from the sarcoplasmic reticulum. Because halothane may cause loss of sequestered Ca2+, the anesthetic was tested for its differential effects on twitch and tetanic forces. The in vitro effects of halothane on the twitch force-interval relationship were then evaluated, using a mathematical model that relates twitch contractile force to the Ca2+ content of intracellular compartments.

METHODS

Isometric contractile force was measured in paced (0.4 Hz) rat atrial preparations. The sarcoplasmic reticulum was functionally eliminated using ryanodine (10(-6) M), abolishing twitches. Rapid pacing (20 Hz, 10 s) caused tetanic contractions. The effects of identical halothane exposures on twitches and tetanic contractions were compared. Ca2+ compartment model parameters were extracted from twitch force-interval data, according to a previously employed quantitative procedure.

RESULTS

Halothane (0.5-1%) depressed normal twitches, but not tetanic contractions. The anesthetic decreased the amplitude of the steady-state twitch force-frequency relationship, and accelerated the course of mechanical recovery. Halothane (0.5-1%) also accelerated the decay constant for the decline in amplitude of a series of rest-potentiated contractions. The modeling showed that a 20-30% decrease in the recirculating fraction of activator Ca2+ accounts for 0.5% halothane-induced negative inotropy and acceleration of the decay constant.

CONCLUSIONS

The differential effect of halothane on twitches and tetanic contractions implies that a functioning sarcoplasmic reticulum is required for halothane-induced negative inotropy. The effects of halothane on the force-interval relationship suggest that halothane reduces the sequestered pool of activator Ca2+.