Effects of enflurane on functionally skinned myocardial fibers from rabbits

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.