Cardiac mTOR protects the heart against ischemia-reperfusion injury.

Cardiac mammalian target of rapamycin (mTOR) is necessary and sufficient to prevent cardiac dysfunction in pathological hypertrophy. However, the role of cardiac mTOR in heart failure after ischemic injury remains undefined. To address this question, we used transgenic (Tg) mice with cardiac-specific overexpression of mTOR (mTOR-Tg mice) to study ischemia-reperfusion (I/R) injury in two animal models: 1) in vivo I/R injury with transient coronary artery ligation and 2) ex vivo I/R injury in Langendorff-perfused hearts with transient global ischemia.

Genetic deletion of NOS3 increases lethal cardiac dysfunction following mouse cardiac arrest.

Study Aims: Cardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival.