Interaction of halogenated anesthetics with alpha- and beta-adrenoceptor stimulations in diabetic rat myocardium

Anesthesiology. 2004 Nov;101(5):1145-52. doi: 10.1097/00000542-200411000-00014.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic beta-Agonists / pharmacology*
  • Algorithms
  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Diabetes Mellitus, Experimental / physiopathology*
  • Drug Interactions
  • Halothane / pharmacology
  • Heart / drug effects*
  • Hydrocarbons, Halogenated / pharmacology*
  • Isoflurane / pharmacology
  • Isoproterenol / pharmacology
  • Male
  • Methyl Ethers / pharmacology
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism
  • Papillary Muscles / drug effects
  • Phenylephrine / pharmacology
  • Rats
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / pathology
  • Sarcoplasmic Reticulum / ultrastructure
  • Sevoflurane

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic beta-Agonists
  • Anesthetics, Inhalation
  • Hydrocarbons, Halogenated
  • Methyl Ethers
  • Phenylephrine
  • Sevoflurane
  • Isoflurane
  • Isoproterenol
  • Halothane