Murine cardiac function: a cautionary tail.

The capacity to selectively mutate genes or create excessive or deleted gene expression in mice has yielded a powerful new approach to structure-function studies of cardiac proteins and their role in heart disease.1 As it happened, the molecular techniques required to generate such animals developed more rapidly than did the methods for studying the chamber physiological phenotype. Mainly because of these methodological limitations, studies to date have often presented hemodynamic data that would fail the standards usually applied in larger species. In particular, heart rates (HRs) and basal levels of systolic contraction are frequently depressed to a substantial degree. It has required a major leap of faith to assume that the physiological differences measured between genetically modified and wild-type animals under such conditions translate to the healthy heart or intact animal. Furthermore, in the understandable rush to assess the impact of molecular manipulations, the careful assessment of normal murine cardiac physiology has been left shortchanged. Only now are we beginning to see the results of such analysis, with evidence growing to support potentially important differences between mice and other mammalian species.2 Such data may be very important for properly interpreting the physiological consequences of targeted genetic manipulations, as reviewed by James et al3 in this issue of Circulation Research . As with larger animals, compromises can and often must be made to balance the need for adequate control to precisely assess cardiac mechanics and physiological intactness to maintain near-normal physiology. Although conscious animal data are often considered the gold standard in larger species, they are not necessarily required to provide relevant or valuable hemodynamic insights. However, awareness of more intact normal physiology has always been critical to properly interpret data obtained in more invasive or isolated heart studies. Rarely has the discrepancy between conscious animal and anesthetized …