The MRL mouse heart does not recover ventricular function after a myocardial infarction

Introduction: Murphy Roth Large (MRL) mice have a remarkable regenerative capacity. A recent report demonstrated rapid cardiac healing in these mice following cryogenically induced right ventricular injury, suggesting the potential for new regenerative therapies to restore cardiac function in mammals. We therefore evaluated the cardiac regenerative wound-healing response and functional recovery of MRL mice in response to a clinically relevant left ventricular coronary ligation. Methods: Female MRL/MpJ(+/+) and C57BL/6 mice underwent left coronary artery ligation. Cardiac function was evaluated by echocardiography at Days 0, 5, 15, and 60. At Day 96, invasive hemodynamics were assessed by pressure-volume loops using a Millar catheter. Hearts were perfusion fixed for histomorphometric analysis at Days 5, 15, and 96. Some hearts were fresh frozen at Days 5 and 15 for immunohistochemical analysis and digital quantitation of blood vessel density (CD31) and cellular proliferation (Ki67). Results: MRL mice healed ear punch wounds (89% reduction in area) more extensively than C57BL/6 mice (28% reduction in area) but did not differ functionally from C57BL/6 animals before or after coronary ligation. In addition, blood vessel density and cell proliferation were similar between the two strains. Conclusions: Although MRL mice rapidly healed ear injury, they did not exhibit regeneration of the left ventricle or enhanced functional improvement in response to coronary ligation. The prospect of cardiac regeneration after myocardial infarction will require further studies designed to elucidate the possible mechanisms of functional restoration. (c) 2008 Elsevier Inc. All rights reserved.