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Published on: September 10, 2015
Calcium transport by cardiac sarcoplasmic reticulum: modulation of halothane action by substrate concentration and pH
Insights
Halothane
Area of Science:
- Cardiology
- Anesthesiology
- Biochemistry
Background:
- Cardiac sarcoplasmic reticulum (SR) calcium transport is crucial for myocardial function.
- Anesthetic agents like halothane can affect cardiac contractility.
- Understanding halothane's impact on SR calcium handling is key to cardiac depression mechanisms.
Purpose of the Study:
- To investigate the effect of halothane on calcium transport by the cardiac sarcoplasmic reticulum.
- To determine if the SR is a site of anesthetic-induced myocardial depression.
Main Methods:
- Studied calcium transport in cardiac SR under varying halothane concentrations.
- Assessed effects of halothane on adenosine triphosphate (ATP) kinetics (Km, Vmax).
- Measured steady-state calcium levels in SR at different pH and substrate concentrations.
Main Results:
- Halothane exhibited biphasic effects on calcium transport, causing both stimulation (800%) and inhibition (500%).
- Halothane altered ATP kinetics, decreasing Km and Vmax for ATP.
- At pH 6.9, halothane reduced SR calcium by 33%; no effect was observed at pH 7.3.
Conclusions:
- The cardiac SR is unlikely to be the primary site of halothane-induced myocardial depression in healthy hearts with normal substrate and pH.
- In ischemic conditions (low pH, low substrate), halothane's interaction with SR calcium transport may contribute to reduced myocardial contractility due to decreased Ca2+ availability.
Abstract:
The response of calcium transport to halothane by the cardiac sarcoplasmic reticulum (SR) was investigated to determine whether the SR is a site for anesthetic depression of the myocardium. It was observed that halothane could both stimulate (by 800%) and inhibit (by 500%) calcium transport. The varied effects are dependent on adenosine triphosphate (ATP) and calcium and hydrogen ion concentrations. At 2.25% halothane, the Km for ATP is decreased from 2.35 to 0.712 mM and Vmax is decreased from 292 to 149 nmoles/mg/2min. It was found that the steady-state level of calcium in the SR was decreased by 33% by halothane at pH 6.9, whereas halothane had no effect at pH 7.3. It was concluded that the SR is an unlikely site of halothane-induced myocardial depression in the normal heart when substrate concentrations and pH are maintained. In the ischemic heart in which the pH and substrate concentration have decreased, the interaction of halothane with the SR might contribute to a decrease in Ca2+ for contraction.
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