Effects of enflurane on functionally skinned myocardial fibers from rabbits.
Enflurance, 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 per cent decrease at 5 per cent 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 per cent decrease at 2.5-7.5 per cent 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 per cent), but was decreased at high concentration (25 per cent decrease at 7.5 per cent enflurane). Enflurane (1-7.5 per cent), however, increased (13-44 per cent) the submaximum caffeine (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.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D003285:Contractile Proteins / Q000378:metabolism; D004737:Enflurane / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism
D002135:Calcium-Binding Proteins; D003285:Contractile Proteins; D004737:Enflurane; D002118:Calcium; D006221:Halothane