Effects of halothane on contraction and intracellular calcium in ventricular myocytes from streptozotocin-induced diabetic rats.
BACKGROUND
Some of the cellular targets affected by volatile anaesthetics (e.g. halothane) which contribute to the negative inotropic effects of these agents are also affected during the progression of diabetic cardiomyopathy. A previous report suggested that halothane inhibited contraction to a lesser extent in papillary muscle from diabetic animals and so the aim of this study was to investigate possible mechanisms underlying this effect.


METHODS
Contractility and cytosolic calcium ion (Ca(2+)) transients were measured (fura-2) in ventricular myocytes isolated from control and streptozotocin (STZ)-induced diabetic rats in the absence and presence of halothane 0.6 mmol litre(-1) at 1 Hz stimulation. Sarcoplasmic reticulum (SR) Ca(2+) content was assessed by rapid application of caffeine. All experiments were carried out at 36-37 degrees C.


RESULTS
The amplitude of shortening, the electrically evoked Ca(2+) transient, SR Ca(2+) content and myofilament Ca(2+) sensitivity, though not altered by STZ treatment, were significantly reduced by halothane to a similar extent in control and STZ myocytes. The time course of contraction and Ca(2+) transient were prolonged in myocytes from STZ-treated rats compared with controls but this was not altered further by halothane. STZ treatment appeared to reduce Ca(2+) efflux from the cell, an effect reversed by halothane.


CONCLUSIONS
In contrast to a previous report, we could find no evidence of amelioration of the negative inotropic effect of halothane in myocytes from the STZ-induced diabetic rat. Contractility, the cytosolic Ca(2+) transient, SR Ca(2+) content and myofilament Ca(2+) sensitivity were qualitatively similar in control and STZ myocytes and were all depressed to the same extent by halothane.
Rithalia
A
A
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Qureshi
M A
MA
Howarth
F C
FC
Harrison
S M
SM
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006221:Halothane / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D018685:Anesthetics, Inhalation; D002118:Calcium; D006221:Halothane