Tomohiro Mizuno1, Richard D Weisel, Ren-Ke Li. 1. Division of Cardiovascular Surgery, Department of Surgery, Toronto General Research Institute, University of Toronto, Toronto General Hospital, 100 Elizabeth Street, Toronto, Ontario M52C4, Canada.
Abstract
OBJECTIVES: Left ventricular assist devices are proposed as a bridge to recovery, but recurrent ventricular deterioration has limited this approach. We describe a new animal model that simulates the effects of left ventricular assist device unloading and then reloading after device removal. The model might facilitate the evaluation of interventions intended to prevent recurrent ventricular dysfunction. METHODS: The hearts and lungs of Lewis rats were removed and transplanted into the abdomen of recipient rats by anastomosing the donor's ascending aorta to the recipient's abdominal aorta. The transplanted hearts were maintained unloaded for 2 weeks in 49 animals. Eighteen transplanted hearts were removed after 2 weeks of unloading. In 17 animals the donor's right pulmonary artery was anastomosed to the recipient's abdominal aorta to reload the heart for an additional 2 weeks. In 14 animals the hearts were maintained unloaded for 4 weeks (an additional 2 weeks). The unloaded and reloaded hearts were compared with normal rat hearts (n = 18). RESULTS: In the unloaded hearts the left ventricular end-diastolic pressures remained low. The left ventricular systolic pressures were lower than the aortic pressures. The left ventricular weights (n = 8) and volumes (n = 4) remained significantly lower ( P < .01) than in the normal hearts. Two weeks after reloading, the left ventricular end-diastolic pressure (n = 8) increased ( P < .01), and the ventricle ejected. The left ventricular systolic pressures exceeded the aortic pressures. The left ventricular weights and volumes increased ( P < .01) and approached those of normal hearts. Matrix metalloproteinase 9 (n = 6/group) levels decreased in the unloaded state ( P = .02) and increased back to normal values after reloading. CONCLUSIONS: This surgical model simulated left ventricular assist device unloading of the left ventricle. The second operation reloaded the left ventricle, which then enlarged. This model will permit the evaluation of adjunctive interventions, such as cell transplantation, intended to facilitate successful left ventricular assist device removal and prevent recurrent dilatation.
OBJECTIVES: Left ventricular assist devices are proposed as a bridge to recovery, but recurrent ventricular deterioration has limited this approach. We describe a new animal model that simulates the effects of left ventricular assist device unloading and then reloading after device removal. The model might facilitate the evaluation of interventions intended to prevent recurrent ventricular dysfunction. METHODS: The hearts and lungs of Lewis rats were removed and transplanted into the abdomen of recipient rats by anastomosing the donor's ascending aorta to the recipient's abdominal aorta. The transplanted hearts were maintained unloaded for 2 weeks in 49 animals. Eighteen transplanted hearts were removed after 2 weeks of unloading. In 17 animals the donor's right pulmonary artery was anastomosed to the recipient's abdominal aorta to reload the heart for an additional 2 weeks. In 14 animals the hearts were maintained unloaded for 4 weeks (an additional 2 weeks). The unloaded and reloaded hearts were compared with normal rat hearts (n = 18). RESULTS: In the unloaded hearts the left ventricular end-diastolic pressures remained low. The left ventricular systolic pressures were lower than the aortic pressures. The left ventricular weights (n = 8) and volumes (n = 4) remained significantly lower ( P < .01) than in the normal hearts. Two weeks after reloading, the left ventricular end-diastolic pressure (n = 8) increased ( P < .01), and the ventricle ejected. The left ventricular systolic pressures exceeded the aortic pressures. The left ventricular weights and volumes increased ( P < .01) and approached those of normal hearts. Matrix metalloproteinase 9 (n = 6/group) levels decreased in the unloaded state ( P = .02) and increased back to normal values after reloading. CONCLUSIONS: This surgical model simulated left ventricular assist device unloading of the left ventricle. The second operation reloaded the left ventricle, which then enlarged. This model will permit the evaluation of adjunctive interventions, such as cell transplantation, intended to facilitate successful left ventricular assist device removal and prevent recurrent dilatation.
Authors: Carolyn A Carr; Daniel Ball; Damian J Tyler; Andrew Bushell; Amelia Sykes; Kieran Clarke; Rhys D Evans Journal: Int J Biomed Sci Date: 2014-12