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 ce llular Ca2+ uptake, whereas twitches depend on Ca2+ release from the s arcoplasmic reticulum. Because halothane may cause loss of sequestered Ca2+, the anesthetic was tested for its differential effects on twitc h 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 int racellular compartments. Methods: Isometric contractile force was meas ured in paced (0.4 Hz) rat atrial preparations. The sarcoplasmic retic ulum was functionally eliminated using ryanodine (10(-6) hr), abolishi ng twitches. Rapid pacing (20 Hz, 10 s) caused tetanic contractions. T he effects of identical halothane exposures on twitches and tetanic co ntractions were compared. Ca2+ compartment model parameters were extra cted from twitch force-interval data, according to a previously employ ed 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%) als o accelerated the decay constant for the decline in amplitude of a ser ies of rest-potentiated contractions. The modeling showed that a 20-30 % decrease in the recirculating fraction of activator Ca2+ accounts fo r 0.5% halothane-induced negative inotropy and acceleration of the dec ay constant. Conclusions: The differential effect of halothane on twit ches and tetanic contractions implies that a functioning sarcoplasmic reticulum is required for halothane-induced negative inotropy. The eff ects of halothane on the force-interval relationship suggest that halo thane reduces the sequestered pool Of activator Ca2+.