Determination of Function in the Isolated Working Mouse Heart: Issues in Experimental Design

The goal of the present study was to compare two common types of isolated working mouse heart models, setting afterload either with (1) a hydrostatic fluid column, or (2) a mechanical resistor. Cardiovascular function in both models was determined by volume- and pressure-loading protocols. During volume loading, both models demonstrated a fixed degree of outflow resistance from the 20-gauge rigid aortic cannula resulting in a small predictable rise in left-ventricular pressure. In the mechanical resistor model, volume loading resulted in a marked increase in afterload, with a >50% increase from baseline aortic pressure. This altered ventricular mechanics, resulting in twice the expected change in dP/dtduring volume loading. Additionally, coronary flow in the mechanical resistor model rose by more than four-fold in parallel to the increased preload. When using the fluid column model, however, aortic pressure was unchanged and coronary flow remained stable. During pressure loading, no significant differences in ventricular mechanics or coronary flow between the mechanical resistor and fluid column models were noted. When mouse hemodynamic data were compared to that from larger species, mouse hearts had similar cardiac function and efficiency with higher MVO2and coronary flows. In summary, the hydrostatic fluid column isolated working mouse heart model is preferred over the mechanical resistor model for studying murine cardiac function. Further, use of this model provides hemodynamic data that is consistent with larger species, albeit with higher MVO2and basal coronary flow, and should allow relevant study of mouse cardiac physiology.