Evaluation of collagenase-induced mitral valve regurgitation in dogs.

OBJECTIVE: To investigate the hemodynamic changes induced by injecting collagenase into the mitral valve to induce mitral valve regurgitation (MVR) in dogs. ANIMALS: 9 healthy Beagles. PROCEDURE: Dogs were randomly assigned to 3 groups: control (saline [0.9% NaCl] solution; n = 3), single collagenase injection (C1; 3), and 2 collagenase injections (C2; 3). Open-heart surgery was performed, and saline or collagenase solutions were injected into the mitral valve. Before and weekly for 11 weeks after surgery, radiography, echocardiography, and phonocardiography were performed. Mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure (mPAWP) were measured before and 11 weeks after surgery. Postmortem examinations were performed after dogs were euthanatized. RESULTS: No changes were detected in the control group during the 11-week follow-up period. A systolic murmur and MVR developed 1 week after surgery in groups C1 and C2. The murmur changed from a protosystolic to a pansystolic murmur, and left atrial diameter and the left atrial-to-aortic root diameter ratio increased with time. Mean pulmonary arterial pressure and mPAWP were greater 11 weeks after surgery in groups C1 and C2, compared with presurgery values. During necropsy, tissue loss was detected in the mitral valve at the site of collagenase injection. Degree of regurgitation corresponded to lesion size. CONCLUSIONS AND CLINICAL RELEVANCE: Injection of collagenase into the mitral valve of healthy dogs induced MVR, and dogs with MVR developed progressive hemodynamic changes without acute overload. Collagenase-induced MVR may be an appropriate model for evaluation of prognostic markers of idiopathic MVR in dogs.