Anesthesia and analgesia
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Anesthesia and analgesia · Oct 1999
Comparative StudyMouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds.
In this study, we measured the minimum alveolar anesthetic concentration (MAC) in several mouse strains, including strains used in the construction of genetically engineered mice. This is important because defined genetic modifications are used increasingly to test mechanisms of inhaled anesthetic action, and background variability in MAC can potentially influence the interpretation of these studies. We investigated the effect of strain on MAC for desflurane, isoflurane, halothane, ethanol, the experimental anesthetic 1-chloro-1,2,2-trifluorocyclobutane, and convulsive 50% effective dose (the dose required to produce convulsions in 50% of animals) of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane. These drugs were studied in eight inbred strains, including both laboratory and wild mouse strains (129/J, 129/SvJ, 129/Ola Hsd, C57BL/6NHsd, C57BL/6J, DBA/2J, Spret/Ei, and Cast/Ei), one hybrid strain (B6129F2/J, derived from the C57BL/6J and 129/J strains), and one outbred strain (CD-1). To test our ability to detect effects in a genetically modified mouse, we compared these data with those for a mouse lacking the gamma (neuronal) isoform of the protein kinase C gene (PKCgamma). We also assessed whether amputating the tail tip of mice (a standard method of obtaining tissue for genetic analysis) increased MAC (e.g., by sensitization of the spinal cord). MAC and convulsant 50% effective dose values differed modestly among strains, with a range of 17% to 39% from the lowest to highest values for MAC using conventional anesthetics, and up to 48% using the experimental anesthetic 1-chloro-1,2,2-trifluorocyclobutane. Convulsivity to the nonimmobilizer varied by 47%. Amputating the tail tip did not affect MAC. PKCgamma knockout mice had significantly higher MAC values than control animals for isoflurane, but not for halothane or desflurane, which implies that protein phosphorylation by PKCgamma can alter sensitivity to isoflurane. ⋯ Anesthetic potency differs by modest amounts among inbred, outbred, wild, and laboratory mouse strains. Absence of the neural form of protein kinase C increases minimum alveolar anesthetic concentration for isoflurane, indicating that protein phosphorylation by the gamma-isoform of protein kinase C (PKCgamma) can influence the potency of this anesthetic.
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Anesthesia and analgesia · Sep 1999
Randomized Controlled Trial Comparative Study Clinical TrialReduction of blood loss and transfusion requirement by aprotinin in posterior lumbar spine fusion.
Aprotinin reduces blood loss in many orthopedic procedures. In posterior lumbar spine fusion, blood loss results primarily from large vein bleeding and also occurs after the wound is closed. Seventy-two patients undergoing posterior lumbar spine fusion were randomly assigned to large-dose aprotinin therapy or placebo. All patients donated three units of packed red blood cells (RBCs) preoperatively. Postoperative blood loss was harvested from the surgical wound in patients undergoing two- and/or three-level fusion for reinfusion. The target hematocrit for RBC transfusion was 26% if tolerated. Total (intraoperative and 24 h postoperative) blood loss, transfusion requirements, and percentage of transfused patients per treatment group were significantly smaller in the aprotinin group than in the placebo group (1935 +/- 873 vs 2809 +/- 973 mL per patient [P = 0.007]; 42 vs 95 packed RBCs per group [P = 0.001]; 40% vs 81% per group [P = 0.02]). Hematological assessments showed an identically significant (a) intraoperative increase in both thrombin-antithrombin III complexes (TAT) and in activated factor XII (XIIa) and (b) decrease in activated factor VII (VIIa), indicating a similar significant effect on coagulation in patients of both groups (P = 0.9 for intergroup comparisons of postoperative VIIa, XIIa, and TAT). Intraoperative activation of fibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P < 0.0001 for intergroup comparison of postoperative D-dimer levels). No adverse drug effects (circulatory disturbances, deep venous thrombosis, alteration of serum creatinine) were detected. Although administered intraoperatively, aprotinin treatment dramatically reduced intraoperative and 24-h postoperative blood loss and autologous transfusion requirements but did not change homologous transfusion in posterior lumbar spine fusion. ⋯ In our study, aprotinin therapy significantly decreased autologous, but not homologous, transfusion requirements in posterior lumbar spine fusion.