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Effects of enflurane on functionally skinned myocardial fibers from rabbits
Abstract:
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.
Insights
Enflurane reduces heart muscle contractility primarily by inhibiting calcium uptake in the sarcoplasmic reticulum (SR). This anesthetic agent affects cardiac muscle function through specific intracellular mechanisms, impacting calcium handling.
Area of Science:
- Cardiology
- Anesthesiology
- Molecular Pharmacology
Background:
- Enflurane is an anesthetic agent known to decrease cardiac muscle contractility at clinical concentrations.
- Understanding the intracellular mechanisms of anesthetic-induced myocardial depression is crucial for patient safety.
Purpose of the Study:
- To investigate the intracellular mechanisms by which enflurane depresses cardiac muscle contractility.
- To examine the effects of enflurane on calcium (Ca2+) activation of contractile proteins and Ca2+ handling by the sarcoplasmic reticulum (SR).
Main Methods:
- Utilized functionally skinned cardiac muscle fibers from rabbit right ventricular papillary muscle.
- Analyzed the Ca2+-tension relationship and caffeine-induced tension transients to assess Ca2+ activation, uptake, and release.
- Controlled intracellular ionic composition (pH 7.0, 20°C) to isolate specific effects.
Main Results:
- Enflurane slightly depressed maximal Ca2+-activated tension but did not alter the Ca2+ sensitivity of contractile proteins.
- Markedly and dose-dependently inhibited Ca2+ uptake by the sarcoplasmic reticulum (SR).
- Altered Ca2+ release from the SR, with inhibition at high concentrations and enhancement at submaximal caffeine stimulation.
Conclusions:
- Enflurane induces myocardial depression primarily by inhibiting Ca2+ uptake into the sarcoplasmic reticulum (SR).
- These findings are comparable to those observed with halothane, suggesting a common anesthetic mechanism.
- The effects of enflurane on cardiac contractility are reversible and linked to sarcoplasmic reticulum Ca2+ handling.