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PubMed · 2020091

[Hepatic circulation and anesthesia].

Abstract

Hepatic artery blood flow changes to buffer portal blood flow alterations, maintaining a constant total hepatic blood flow. Portal blood flow is regulated by preportal organs, such as intestine, pancreas and spleen. The liver plays an important role as a blood reservoir for cardiovascular homeostasis. Hepatic blood volume is mobilized actively to the systemic circulation by sympathetic stimulation. Sinusoid, the specialized capillary of the liver, and Disse's space are separated by endothelial cells, which have numerous fenestrations, allowing effective exchanges of solutes between hepatocytes and blood. Unidirectional blood flow in the acinus causes functional differences of hepatocytes according to the lobular zones. Although the majority of anesthetics decreases liver blood flow in a dose dependent manner, halothane inhibits hepatic arterial buffer response, while isoflurane and narcotics preserve it. Energy depletion, cellular acidosis, alteration of calcium homeostasis and superoxide-induced membrane damage, are all implicated as important factors for ischemia-induced liver injury. A better understanding of ischemia-induced derangements of cell function will lead to more rational preservation of the liver cells in the future.

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BibTeXRIS

Y Fujita, M Takaori. 1991. [Hepatic circulation and anesthesia].. https://pubmed.ncbi.nlm.nih.gov/2020091/

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Anesthetics↗

Identification of a molecular target mediating the general anesthetic actions of pentobarbital.

Barbiturates were introduced into medical practice in 1934. They are widely used today as general anesthetics. Although in vitro studies revealed that the activity of a variety of ligand-gated channels is modulated by barbiturates, the target(s) mediating the anesthetic actions of barbiturates in vivo are unknown. Studying pentobarbital action in beta3(N265M) mice harboring beta3-containing GABAA receptors insensitive to a variety of general anesthetic agents, we found that the immobilizing action of pentobarbital is mediated fully, and the hypnotic action is mediated in part by this receptor subtype. It was surprising that the respiratory depressant action of pentobarbital is indistinguishable between beta3(N265M) and wild-type mice and thus is mediated by other as-yet-unidentified targets. Whereas the target for the immobilizing and hypnotic actions of pentobarbital seems to be the same as for etomidate and propofol, these latter agents' respiratory depressant actions are mediated by beta3-containing GABAA receptors. Thus, in contrast to etomidate and propofol, pentobarbital can elicit respiratory depression by a beta3-independent pathway. Pentobarbital reduced heart rate and body temperature to a slightly smaller extent in beta3(N265M) mice compared with wild-type mice, indicating that these actions are largely mediated by other targets. Pentobarbital-induced increase of heart rate variability and prolongation of ECG intervals are seen in both beta3(N265M) mice and wild-type mice, suggesting that they are not dependent on beta3-containing GABAA receptors. In summary, we show a clear pharmacological dissociation of the immobilizing/hypnotic and respiratory/cardiovascular actions of pentobarbital.

Anesthetics↗