Mouse Survival Surgery and Cardiovascular Models


The murine physiology laboratory has developed models that allow the evaluation of genetic interventions in cardiac function, response to load, inflammation, fibrosis and repair. The common strategy of all of these models is that they are created surgically in sophisticated operating suites within the murine physiology core utilizing anesthesia equipment developed for survival surgery. The animals are allowed to recover from anesthesia and cardiac surgery so that they are studied in the chronic state. In some cases, cannulae where infusion pumps may be inserted.

This laboratory pioneered the utilization of this strategy in the study of acute myocardial infarction and demonstrated the effectiveness and necessity of cardiac healing from surgical trauma before introduction of the experimental intervention [Entman et al, 2000; Nossuli et al, 2000]. Each of the models described has been useful in several major studies involving the publication in high impact journals.

We have primarily directed our technology to study mice acutely and chronically and have developed new instrumentation and procedures to that end. We also have developed a model of I/R in the mouse that allows long term survival [Michael et al, 1995]; in subsequent studies, we devised methods to analyze and correlate LV function with infarct expansion [Gould et al, 2002; Michael et al, 1999]. Finally, we developed a closed chest I/R model in the mouse that allows dissipation of surgical trauma and use this model for repeated I/R episodes on the same mouse [Dewald et al, 2003; Nossuli et al, 2000].

These models have been transferred to multiple laboratories but the core still serves investigators from 20-25 other laboratories each year with which we collaborate or that are unable to institute either the model technology or the instrumentation technology in their own institution. Thus, this core extends services throughout the cardiovascular community, a property which leads to collaborations and broadens our experimental horizons.