Cardiac output, at rest and during exercise, before and during myocardial ischemia, reperfusion, and infarction in conscious mice

Abstract

Multiple systems and regulatory strategies interact to control cardiac homeostasis. In fact, regulated systems, feedback controls, and redundant control mechanisms dominate in whole animals. Accordingly, molecular and cellular tools and techniques must be utilized in complex models with multiple systems and regulatory strategies to fully appreciate the physiological context. Currently, these techniques are mainly performed under conditions remote from the normal in vivo condition; thus, the extrapolation of molecular changes to the in vivo situation and the facilitation of translational aspect of the findings are limited. A major obstacle has been the reliance on preparations that do not mimic the clinical or physiological situation. This is particularly true regarding measurements of cardiac function in mice. To address these concerns, we used a permanently implanted Doppler ultrasonic flow probe on the ascending aorta and coronary artery occluder for repeated measurements of ascending aortic blood flow (cardiac output) in conscious mice, at rest and during exercise, before and during coronary artery occlusion/reperfusion and infarction. The conscious mouse model permits detailed monitoring of within-animal changes in cardiac function during myocardial ischemia, reperfusion, and infarction in an intact, complex model free of the confounding influences of anesthetics, surgical trauma, and restraint stress. Results from this study suggest that previous protocols may have overestimated resting baseline values and underestimated cardiac output reserve. Using these procedures in currently available spontaneous or engineered mouse mutants has the potential to be of major importance for advancing the concepts and methods that drive cardiovascular research.