ABNORMAL ACTION-POTENTIAL RESPONSES TO HALOTHANE IN HEART-MUSCLE ISOLATED FROM MALIGNANT HYPERTHERMIA-SUSCEPTIBLE PIGS

Background: During human and porcine malignant hyperthermia (MH), card iac dysrhythmias and altered myocardial function can be observed. It i s unknown whether a primary abnormality in cardiac muscle contributes to the cardiac symptoms during MH. An abnormal response to halothane h as recently been demonstrated in action potentials (APs) from MH-susce ptible (MHS) human skeletal muscles. We investigated the electrophysio logic properties in trabeculae isolated-from the right ventricles of n ormal (MHN) and MHS pigs. Methods: The experiments were performed on e lectrically stimulated (1 Hz) trabeculae isolated from the right ventr icles of MHS and MHN pigs. Resting membrane potentials, APs, and tensi on were measured with and without the presence of 1% halothane, In add ition, the halothane-equilibrated muscles were exposed to caffeine in increasing doses (1, 2, and 4 mM). Results: In the absence of halothan e, resting potential and AP characteristics in MHS and MHN muscles did not differ significantly. Halothane did not alter resting potentials but produced different alterations in the APs in MHS and MHN muscles, whereas the decrease in twitch tension was identical. In contrast to r eductions in the AP amplitude and duration in MHN muscle, halothane pr oduced an enlargement of the APs in MHS muscle. The addition of caffei ne caused nearly identical prolongations of AP duration in MHS and MHN muscles. Conclusions: This in vitro study demonstrates that halothane produces abnormal alterations in the dynamic electric properties of t he ventricular excitable membrane from MHS pigs, These results suggest a latent defect in the myocardium of MHS pigs that becomes apparent i n the presence of MH-triggering agents.