title: Halothane alters contractility and Ca2+ transport in ventricular myocytes from streptozotocin-induced diabetic rats.
abstract: General anaesthetics have previously been shown to have profound effects on myocardial function. Moreover, many patients suffering from diabetes mellitus are anaesthetised during surgery. This study investigated compromised functioning of cardiac myocytes from streptozotocin (STZ)-induced diabetic rats and the additive effects of halothane on these dysfunctions. Ventricular myocytes were isolated from 8 to 12 weeks STZ-treated rats. Contraction and intracellular free calcium concentration ([Ca2+]i) were measured in electrically field-stimulated (1 Hz) fura-2-AM-loaded cells using a video-edge detection system and a fluorescence photometry system, respectively. L-type Ca2+ current was measured in whole cell, voltage-clamp mode. Halothane significantly (p < 0.01) depressed the amplitude and the time course of the Ca2+ transients in a similar manner in myocytes from control and STZ-treated rats. However, the effect of halothane on the amplitude of shortening and L-type Ca2+ current was more pronounced in myocytes from STZ-treated animals compared to age-matched controls. Myofilament sensitivity to Ca2+ was significantly (p < 0.01) increased in myocytes from STZ-treated rats compared to control. However, in the presence of halothane the myofilament sensitivity to Ca2+ was significantly (p < 0.05) reduced to a greater extent in myocytes from STZ-treated rats compared to controls. In conclusion, these results show that contractility, Ca2+ transport and myofilament sensitivity were all altered in myocytes from STZ-treated rats and these processes were further altered in the presence of halothane suggesting that hearts from STZ-induced diabetic rats are sensitive to halothane.
authors.affiliation: Department of Biological Sciences, University of Central Lancashire, Preston, England, UK.
authors.forename: Alyson
authors.initials: A
authors.lastname: Woodall
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bracken
authors.forename: Anwar
authors.initials: A
authors.lastname: Qureshi
authors.forename: Frank Christopher
authors.initials: FC
authors.lastname: Howarth
authors.forename: Jaipaul
authors.initials: J
authors.lastname: Singh
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D006221:Halothane / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009210:Myofibrils / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018685:Anesthetics, Inhalation; D020746:Calcium Channels, L-Type; D002118:Calcium; D006221:Halothane