Non-invasive echocardiographic studies in mice - Influence of anesthetic regimen

Transgenic murine models of cardiovascular disease offer great potential in sights regarding mechanisms of human disease, but efficient and reliable me thods for phenotype evaluation are necessary. We employed non-invasive echo cardiography to evaluate hemodynamic parameters in mice, and evaluated stat istical reliability of these parameters with respect to anesthesia regimen. Male CF-1 mice received inhaled halothane (0.25-0.75% in 95% O-2) or ketam ine/xylazine (80/10mg/kg i.p.) and 2-dimensional, M-mode, and Doppler ultra sound imaging were used to assess cardiac contractility and aortic flow vel ocities. Halothane was more convenient and reliable with respect to rate of induction, reversal, and control of anesthetic depth. At comparable levels of anesthesia, ketamine/xylazine produced significant reductions in heart rate (308 +/- 14 vs. 501 +/- 14 bpm, p <0.001), left ventricular fractional shortening (41.7 +/- 1.3 vs. 49.3 +/- 1.0%, p <0.001), and cardiac output (7.6 +/- 0.5 vs. 11.5 +/- 0.6 ml/min, p <0.001) when compared to halothane inhalation. No change in stroke volume or peak aortic velocity was observed . Correlation analyses revealed highly significant positive relationships b etween heart rate and fractional shortening (r = 0.61, p <0.002) and cardia c output (r = 0.88, p <0.001) but no relation to stroke volume or aortic ve locity. Variability of intra-animal and intragroup parameter estimation wer e frequently 2-fold larger for keramine/xylazine anesthesia vs. halothane. Statistical power analysis showed the increased measurement error for ketam ine/xylazine leads to much larger numbers of mice/group to achieve identica l statistical sensitivity. These data further illustrate the feasibility of echocardiography for rapid, non-invasive cardiovascular assessment in mice . However, several obtainable parameters are highly sensitive tol both hear t rate and anesthetic used and the choice and control of anesthetic are cri tical for physiologically relevant performance parameters and maximal abili ty to detect statistical differences among groups. Thus, for these non-inva sive studies, inhalation anesthesia with agents such as halothane is superi or to anesthesia induced by ketamine/xylazine administration. (C) 2001 Else vier Science Inc. All rights reserved.