Enflurane, at clinical concentrations, decreases the contractility of isolated intact cardiac muscle. The authors investigated the intracellular mechanism(s) of this depression by examining the Ca2+ activation of the contractile proteins and Ca2+ uptake and release from the sarcoplasmic reticulum (SR) using functionally skinned fibers from right ventricular papillary muscle of rabbits. This preparation permits control of intracellular ionic composition (pH 7.0, 20°C). The [Ca2+]-tension relationship and caffeine-induced tension transient (as a measure of the amount of Ca2+ release) were analyzed. Enflurane significantly but only slightly depressed the maximum Ca2+-activated tension (10% decrease at 5% enflurane) and did not change the [Ca2+] required for half-maximal activation of the fibers. In contrast, enflurane markedly inhibited the Ca2+ uptake by the SR (30-85% decrease at 2.5-7.5% enflurane). The inhibition was dose-dependent. Ca2+ release from the SR with 25 mM caffeine was not changed at low concentrations of enflurane (1-5%), but was decreased at high concentration (25% decrease at 7.5% enflurane). Enflurane (1-7.5%), however, increased (13-44%) the submaximum caffine (2 mM)-induced Ca2+ release from the SR, and the effect was not dose-dependent. The aforementioned effects were reversible. These results are similar to those previously reported for halothane. It is concluded that enflurane may induce myocardial depression mainly by inhibiting Ca2+ uptake by the SR.
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine