Interaction of halogenated anesthetics with alpha- and beta-adrenoceptor stimulations in diabetic rat myocardium.
BACKGROUND
Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown.


METHODS
Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD.


RESULTS
Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P < 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P < 0.05) and sevoflurane (161 +/- 40%; P < 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane.


CONCLUSIONS
Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.
Amour
Julien
J
Department of Anesthesiology, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France.
David
Jean-Stéphane
JS
Vivien
Benoît
B
Coriat
Pierre
P
Riou
Bruno
B
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004347:Drug Interactions; D006221:Halothane / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D000077149:Sevoflurane
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D018685:Anesthetics, Inhalation; D006846:Hydrocarbons, Halogenated; D008738:Methyl Ethers; D010656:Phenylephrine; D000077149:Sevoflurane; D007530:Isoflurane; D007545:Isoproterenol; D006221:Halothane