British Journal of Anaesthesia, Vol 82, Issue 4 609-621, Copyright © 1999 by The Board of Management and Trustees of the British Journal of Anaesthesia
S. M. Harrison, M. Robinson, L. A. Davies, P. M. Hopkins and M. R. Boyett
The mechanisms contributing to the negative inotropic effect of halothane
were studied in isolated rate ventricular myocytes. Contraction and
intracellular Ca2+ transients were measured optically in these cells. The
initial application of halothane (2% or 0.5 mmol litre-1) led to
short-lived increases in the Ca2+ transient and contraction, which were
abolished by ryanodine. Continued application of halothane led to a
sustained decrease in contraction: this resulted from: (i) a decrease in
myofilament Ca2+ sensitivity; (ii) a decrease in the Ca2+ transient; and
(iii) a decrease in the Ca2+ content of the sarcoplasmic reticulum.
Although halothane reduced action potential duration, the sustained
negative inotropic effect was similar when action potentials or voltage
clamp pulses of constant duration were used to trigger contractions. In
cells exposed to nifedipine 0.5 microgramsmol litre-1 (which decreases the
L-type Ca2+ current, ICa), Ca2+ transients, sarcoplasmic reticulum Ca2+
content and fractional release (the fraction of sarcoplasmic reticulum Ca2+
content released during each stimulus) were reduced. Halothane 0.5 mmol
litre-1 (which also decreases ICa) decreased Ca2+ transients to a lesser
extent and reduced sarcoplasmic reticulum Ca2+ content to a greater extent
than nifedipine, whereas fractional release was unchanged compared with
control. These data suggest that halothane sensitizes Ca(2+)-induced Ca2+
release from the sarcoplasmic reticulum in addition to reducing ICa.
LABORATORY INVESTIGATIONS
Mechanisms underlying the inotropic action of halothane on intact rat ventricular myocytes
School of Biomedical Sciences and Academic Unit of Anaesthesia, University of Leeds, Leeds LS2 9JT, UK
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