Effects of ketamine on hypoxic pulmonary vasoconstriction in the isolated perfused lungs of endotoxaemic mice
- 1 January 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in European Journal of Anaesthesiology
- Vol. 27 (1), 61-66
- https://doi.org/10.1097/eja.0b013e328329affb
Abstract
Background and objective During sepsis and endotoxaemia, hypoxic pulmonary vasoconstriction (HPV) is impaired. Sedation of septic patients in ICUs is performed with various anaesthetics, most of which have pulmonary dilatory properties. Ketamine is a sympathetic nervous system-activating anaesthetic that preserves cardiovascular stability. The effects of ketamine on the pulmonary vasculature and HPV during sepsis have not been characterized yet. Methods Therefore, isolated lungs of mice were perfused with ketamine (0, 0.1, 1.0, and 10 mg kg−1 body weight min−1) 18 h following intraperitoneal injection of lipopolysaccharide (LPS); untreated mouse groups served as controls (n = 7 per group, respectively). Pulmonary artery pressure (PAP) and pressure–flow curves during normoxic (FiO2 = 0.21) and hypoxic (FiO2 = 0.01) ventilation were obtained. Results HPV was reduced in endotoxaemic animals when compared with controls (means ± SD; ΔPAP control 103 ± 28% vs. LPS 23 ± 25%, P < 0.05). Ketamine caused a dose-dependent reduction of HPV in the lungs of control (ΔPAP 0 mg kg−1 min−1 ketamine 103 ± 28% vs. 10 mg kg−1 min−1 ketamine 28 ± 21%, P < 0.05) and septic animals (ΔPAP 0 mg kg−1 min−1 ketamine 23 ± 25% vs. 10 mg kg−1 min−1 ketamine 0 ± 4%, P < 0.05). Analysis of pressure–flow curves revealed that ketamine partly reversed the endotoxin-induced changes in basal pulmonary vascular wall properties rather than interfering with the HPV response itself. Conclusion Ketamine modified baseline pulmonary vascular properties, resulting in a reduced HPV responsiveness in untreated mice. Further, ketamine counteracted the LPS-induced changes in pulmonary vascular pressure–flow relationships, but did not affect impaired HPV in this murine endotoxaemia model.Keywords
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