An Optimal Physiologic Model for Study of Murine Cardiac Function Under Inhalational Anesthesia

Christakis Constantinides¹, Richard Mean¹, Laurence W. Hedlund²

While cardiac mechanical functional studies initially focused on large mammals and the human, the mouse emerged as the preferred animal species for research in recent years. Albeit evidence supports that bioenergetically and hemodynamically the mouse scales linearly with larger mammals and humans, important physiological questions still remain for the appropriateness of this model for extrapolation of conclusions to man. Since the complete characterization of the mouse and human genomes in 2002 and 2003 respectively, there has been a plethora of transgenic mouse studies targeting the cardiovascular system. Equally important were non-invasive imaging studies of such animals for phenotypic and genotypic screening, often conducted under inhalational anesthesia. Anesthetics, however, are known to cause severe cardio-depression with adverse physiological effects on hormonal release, centrally to the heart and peripherally to the vasculature, at the cellular level, affecting calcium entry through L-type Ca2+ channels, the calcium binding sensitivity of the contractile proteins to calcium, and on conduction and excitability. The objective of this study was to determine the isoflurane dose in normal mice for optimal physiological status (respiration, cardiac function, and metabolism) for a period of 1-2 hours post-induction, facilitating migration of such work to the non-invasive imaging platform of MRI, with tremendous potential for future basic science towards the phenotypic screening of transgenic mice and translational research.