Abstract
The selection of the anesthetic regime is a crucial component in many experimental animal studies. In rodent models of liver disease, the combination of ketamine and diazepam (KD), generally by the intramuscular (i.m.) route, has traditionally been the anesthesia of choice for the evaluation of systemic and hepatic hemodynamics but it presents several problems. Here, we compared the performance of inhalational sevoflurane (Sevo) against the KD combination as the anesthesia used for hemodynamic studies involving the measurement of portal pressure in normal rats (Ctrl) and rats with non-cirrhotic portal hypertension induced by partial portal vein ligation (PPVL). Compared with Ctrl rats, rats with PPVL presented characteristic alterations that were not influenced by the anesthetic regime, which included liver atrophy, splenomegaly, increased plasma fibrinogen, decreased alkaline phosphatase and glycemia, and frequent ascites. The use of the KD combination presented several disadvantages compared with the inhalational anesthesia with sevoflurane, including considerable mortality, a higher need of dose adjustments to maintain an optimal depth of anesthesia, increases of heart rate, and alteration of blood biochemical parameters such as the concentration of aspartate aminotransferase, lactate, and lactic dehydrogenase. Rats anesthetized with sevoflurane, on the other hand, presented lower respiratory rates. Importantly, the anesthetic regime did not influence the measurement of portal pressure either in Ctrl or PPVL rats, with the increase of portal pressure being similar in Sevo- and KD- anesthetized groups of PPVL rats compared with their respective control groups. Overall, our results suggest that anesthesia with sevoflurane is preferable to the combination of KD for performing systemic and hepatic hemodynamic studies in rats with non-cirrhotic portal hypertension.
Highlights
Liver cirrhosis—the end-stage of chronic liver diseases—represents a significant healthcare problem with associated mortality that is similar to that of major cancers [1]
Splanchnic blood flow was lower in enflurane and similar among the rest of anesthetics; but hepatic arterial blood flow (HABF) was similar in conscious rats, isoflurane and halothane groups, and lower with ketamine
mean arterial pressure (MAP) was significantly higher in the ketamine and isoflurane compared with the enflurane and halothane groups
Summary
Liver cirrhosis—the end-stage of chronic liver diseases—represents a significant healthcare problem with associated mortality that is similar to that of major cancers [1]. Much of our understanding of the pathophysiology of portal hypertension has been generated in experimental models in rats because they allow direct measurements of portal pressure and regional blood flows. Ketamine with or without a benzodiazepine, generally administered intramuscularly (i.m.) instead of intraperitoneally (i.p.) to avoid direct effects of anesthetics on splanchnic vessels, has been the anesthesia of choice in most studies involving measurement of portal pressure in rodents [3,4,5,6,7,8,9]. Most anesthetics are metabolized in the liver, which introduces a relevant additional factor for studies of cirrhosis and portal hypertension as the effects of anesthetics may vary between experimental groups depending on the absence or presence of different degrees of liver dysfunction
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