Anesthesia and Intubation of Preadolescent Mouse Pups for Cardiothoracic Surgery.

Murine surgical models play an important role in preclinical research. Mechanistic insights into myocardial regeneration after cardiac injury may be gained from cardiothoracic surgery models in 0-14-day-old mice, the cardiomyocytes of which, unlike those of adults, retain proliferative capacity. Mouse pups up to 7 days old are effectively immobilized by hypothermia and do not require intubation for cardiothoracic surgery.

Pressure overload by suprarenal aortic constriction in mice leads to left ventricular hypertrophy without c-Kit expression in cardiomyocytes.

Animal models of pressure overload are valuable for understanding hypertensive heart disease. We characterised a surgical model of pressure overload-induced hypertrophy in C57BL/6J mice produced by suprarenal aortic constriction (SAC). Compared to sham controls, at one week post-SAC systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was evident by a 50% increase in the LV weight-to-tibia length ratio due to cardiomyocyte hypertrophy.

Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice.

We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI) due to coronary artery ligation are improved in this transgenic model. Compared to non-transgenic littermates (NTLs), adult male dn-c-kit-Tg mice displayed CM hypertrophy and concentric left ventricular (LV) hypertrophy in the absence of an increase in workload.

Comparative regenerative mechanisms across different mammalian tissues.

Stimulating regeneration of complex tissues and organs after injury to effect complete structural and functional repair, is an attractive therapeutic option that would revolutionize clinical medicine. Compared to many metazoan phyla that show extraordinary regenerative capacity, which in some instances persists throughout life, regeneration in mammalians, particularly humans, is limited or absent. Here we consider recent insights in the elucidation of molecular mechanisms of regeneration that have come from studies of tissue homeostasis and injury repair in mammalian tissues that span the spectrum from little or no self-renewal, to those showing active cell turnover throughout life.