A CANINE MODEL OF CHRONIC MITRAL VALVE REGURGITATION WITH PRESERVATION OF RESTING CARDIAC FUNCTION

Abstract

Background: The purpose of this study was to develop a canine model of chronic dilated cardiomyopathy with preservation of resting cardiac function. Methods: The baseline cardiac geometry and function of eight mongrel dogs (20–22 kg) were evaluated using transthoracic echocardiography (TTE). A right atrial pacer lead was implanted, and mild MR was produced through a fixed lesion to the mitral valve apparatus. Incremental pacing induced LV dilation over an eight-month period. The pacer was deactivated and the dogs followed for an additional six weeks. The heart was arrested in diastole and myocytes were examined histo-logically. All animals were evaluated in-vivo at baseline, following acute MR, at the end of pacing and at explant. TTE evaluations were performed hi-weekly. Similar studies were performed in six control dogs. Results: TTE data demonstrated significant changes in LV and LA geometry, which were sustained following pacing deactivation. MR severity increased significantly, whereas baseline cardiac function was preserved. There was preservation of stroke volume and systemic pressures with a significant increase in pulmonary capillary wedge pressure. Cardiac function decreased significantly at increased pacing rates. Isolated myocytes demonstrated significant cellular enlargement from control studies with increased cell area and volumes. Conclusion: The methodology presented represents a novel model of chronic MR with preservation of baseline cardiac function. Our results demonstrate progressive cardiac remodelling and worsening MR without significant changes in EF or stroke volume.