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+.
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D013746:Tetany / Q000139:chemically induced*
D018685:Anesthetics, Inhalation; D002118:Calcium; D006221:Halothane