No abstract

Introduction: Mitral regurgitation (MR) developing secondary to a myocardial infarction(MI) is a clinical challenge, as its impact on adverse ventricular remodeling and dysfunction, and the role of mitral repair remains unknown. Using a novel rodent model, we sought to investigate the impact of MR on left ventricular remodeling and failure. Hypothesis: MR accelerates post-MI remodeling and impairs systolic function. Methods: Adult rats (~300g, N =49) were randomized to four groups: MR only(n=15); MR + MI (n=11); MI only(n=11); and sham(n=12). MR was induced by puncturing the mitral valve leaflet with a 23g needle inserted transapically into the beating heart with TEE guidance. MI was induced by permanent ligation of the left coronary artery. After 90-days of follow-up, TTE and invasive pressure-volume loops were obtained and the tissue collected. Data are presented as mean ± 1 standard deviation, and ANOVA was used for group comparison. Results: Ejection fraction significantly reduced from 56.6 ± 10.7% in sham to 42.5 ±18.4% in MR, 42.6 ± 15.4% in MR +MI, and 37.5 ± 19.3% in MI groups (p<0.05). ESV and EDV were significantly higher than sham in all the experimental groups, with MR+MI having the highest ventricular volumes. The slope of end systolic pressure-volume relationship (ESPVR) in MR, MI and MR+MI groups were 0.36± 0.19, 0.53±0.37, and 0.44±0.20 mmHg/μl, respectively, all of which were significantly reduced than sham(1.8 ±1.6 mmHg/μl), as shown in Figure 1. MI and MR+MI groups showed elevated left ventricular end-diastolic pressure (11.8± 3.3, 12.0 ±5.6 mmHg, respectively) compared to sham group (8.4 ±2.1mmHg). However, dP/dt min, Tau Weiss and Tau Glantz were unchanged. Conclusions: Systolic function is most compromised in MR+MI group compared to MR alone or MI alone at 90-days, whereas diastolic function was moderately impaired. This rat model provides a new platform to study the therapeutic impact of different drugs on ventricular function in this valve lesion.