Respiratory effects of commonly used anesthesia regimes in rats

Introduction: Respiratory parameters of experimental animals are assessed mainly under general anesthesia, however the anesthesia itself may alter the functional and mechanical properties of the respiratory system. While different anesthesia regimes have been shown to differ in their respiratory consequences, the effects of anesthesia protocols commonly used in animal models on the lung function have not been systematically compared. Methods: 40 male Sprague-Dawley rats were divided into 5 groups, each group undergoing different anesthesia regimes: intravenous (iv) pentobarbital, intraperitoneal (ip) ketamine-xylazine, iv propofol-fentanyl, inhaled sevoflurane, and ip urethane, with all drugs applied in commonly used doses. End-expiratory lung volume (EELV), airway resistance (Raw), and tissue mechanics were measured during mechanical ventilation at 3 different PEEP levels, 0, 3, and 6 cmH2O. Respiratory mechanics were then measured following iv methacholine (MCh) challenges to assess airway hyperresponsiveness (AH). Results: While PEEP affected baseline respiratory mechanics and EELV (p<0.001), no between-group differences were observed (p>0.13). A tendency for lower Raw was seen under sevoflurane at high PEEP (p=0.08). Significantly lower MCh doses were needed for the same elevation in Raw under ketamine-xylazine compared to the other groups. Conclusions: Baseline respiratory effects of commonly used anesthesia drugs do not differ. The clinically relevant bronchodilating effect of sevoflurane was not confirmed, probably due to the lack of an elevated bronchial smooth muscle tone. The ketamine-xylazine induced AH should be considered while designing experiments with this anesthesia regime. Funding: OTKA-NKFIH FK134274