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

Introduction: 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 [1]. Albeit evidence supports that bioenergetically and hemodynamically the mouse scales linearly with larger mammals and humans [2; 3], important physiological questions still remain for the appropriateness of this model for extrapolation of conclusions to man [4, 5]. Since the complete characterization of the mouse and human genomes in 2002 and 2003 respectively [1], there has been a plethora of transgenic mouse studies targeting the cardiovascular system [6; 7]. Equally important were non-invasive imaging studies of such animals for phenotypic and genotypic screening, often conducted under inhalational anesthesia [8-12]. Anesthetics, however, are known to cause severe cardio-depression [9] with adverse physiological effects on hormonal release, centrally to the heart and peripherally to the vasculature [10; 11], at the cellular level, affecting calcium entry through L-type Ca channels, the calcium binding sensitivity of the contractile proteins to calcium, and on conduction and excitability [10]. 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.