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Volatile anaesthetic effects on Na⁺-Ca²⁺ exchange in rat cardiac myocytes

Inanc Seckin *, Gary C. Sieck *† and Y. S. Prakash *

1. We examined the influence of two clinically relevant concentrations (1 and 2 MAC (minimum alveolar concentration)) of halothane and sevoflurane on both efflux and reverse modes of Na⁺-Ca²⁺ exchange (NCX) in enzymatically dissociated adult rat cardiac myocytes. We hypothesised that a volatile anaesthetic-induced decrease in myocardial contractility is mediated by a reduction in intracellular calcium concentration ([Ca²⁺]_i) via inhibition of NCX.

2. Cells were exposed to cyclopiazonic acid and zero extracellular Na⁺ and Ca²⁺ to block sacroplasmic reticulum (SR) re-uptake and NCX efflux, respectively. As [Ca²⁺]_i increased under these conditions, extracellular Na⁺ was rapidly (< 300 ms) reintroduced in the presence or absence of a volatile anaesthetic to selectively promote Ca²⁺ efflux via NCX. Other cells exposed to cyclopiazonic acid and ryanodine to inhibit SR Ca²⁺ re-uptake and release were Na⁺ loaded in zero extracellular Ca²⁺. The reintroduction of extracellular Ca²⁺ was used to selectively activate Ca²⁺ influx via NCX.

3. Compared to controls, both 1 and 2 MAC halothane as well as sevoflurane reduced NCX-mediated efflux. The reduction in NCX-mediated influx was concentration dependent, but comparable between the two anaesthetics. Both anaesthetics at each concentration also shifted the relationship between extracellular Na⁺ (or extent of Na⁺ loading) and NCX-mediated efflux (or influx) to the right.

4. These data indicate that despite inhibition of NCX-mediated Ca²⁺ efflux, volatile anaesthetics produce myocardial depression. However, the inhibition of NCX-mediated Ca²⁺ influx may contribute to decreased cardiac contractility. The overall effect of volatile anaesthetics on the [Ca²⁺]_i profile is likely to be determined by the relative contributions of influx vs. efflux via NCX during each cardiac cycle.

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