Direct Actions of Volatile Anesthetics on the Coronary Vasculature

Abstract Volatile anesthetics affect all cells and tissues tested, but their mechanisms and sites of action remain unknown. To gain insight into the cellular activities of anesthetics, we have isolated genes that, when overexpressed, render Saccharomyces cerevisiae resistant to the volatile anesthetic isoflurane. One of these genes, WAK3/TAT1, encodes a permease that transports amino acids including leucine and tryptophan, for which our wild-type strain is auxotrophic. This suggests that availability of amino acids may play a key role in anesthetic response. Multiple lines of evidence support this proposal: (i) Deletion or overexpression of permeases that transport leucine and/or tryptophan alters anesthetic response; (ii) prototrophic strains are anesthetic resistant; (iii) altered concentrations of leucine and tryptophan in the medium affect anesthetic response; and (iv) uptake of leucine and tryptophan is inhibited during anesthetic exposure. Not all amino acids are critical for this response since we find that overexpression of the lysine permease does not affect anesthetic sensitivity. These findings are consistent with models in which anesthetics have a physiologically important effect on availability of specific amino acids by altering function of their permeases. In addition, we show that there is a relationship between nutrient availability and ubiquitin metabolism in this response.

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Anesthetic Effects on Mitochondrial ATP-sensitive K Channel

Anesthesiology ◽

10.1097/00000542-200112000-00024 ◽

2001 ◽

Vol 95 (6) ◽

pp. 1435-1440 ◽

Cited By ~ 80

Author(s):

Shinji Kohro ◽

Quinn H. Hogan ◽

Yuri Nakae ◽

Michiaki Yamakage ◽

Zeljko J. Bosnjak

Keyword(s):

Fluorescence Microscopy ◽

Volatile Anesthetics ◽

Cardioprotective Effect ◽

K Channel ◽

Myocardial Cells ◽

Intravenous Anesthetics ◽

Inhalational Anesthetics ◽

Cardioprotective Effects ◽

Cardiac Preconditioning ◽

Dose Dependent

Background Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation. Methods Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured. Results Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation. Conclusions Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.

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Automated extraction, labelling and analysis of the coronary vasculature from arteriograms

The International Journal of Cardiac Imaging ◽

10.1007/bf01137902 ◽

1994 ◽

Vol 10 (3) ◽

pp. 205-215 ◽

Cited By ~ 15

Author(s):

Adrie C. M. Dumay ◽

Jan J. Gerbrands ◽

Johan H. C. Reiber

Keyword(s):

Automated Extraction ◽

Coronary Vasculature

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