Cardiomyoplasty Improves Contractile Reserve after Myocardial Injury in Mice: Functional and Morphological Investigations with Reconstructive Three-Dimensional Echocardiography

Abstract

Cellular cardiomyoplasty (CMP) is a novel therapeutic approach to myocardial injury (MI). Post-MI remodeling of the left ventricle (LV) comprises dilatation and impairment of systolic function and gives rise to progressive hemodynamic deterioration. We aimed to investigate: a) the impact of CMP on global and regional parameters of LV remodeling (LVR) as well as contractile reserve and b) the suitability and validity of different echocardiographic methods in this scenario. Murine ventricular cardiomyocytes (E13.5-E16.5) were transplanted into cryolesioned hearts of male HIM-OF1 mice. Echocardiography was performed at rest 4 and 14 days postoperatively. For quantification of akinetic myocardial mass and contractile reserve 2 weeks postoperatively additionally low-dose dobutamine stress echocardiography was conducted. Reconstructive 3D-echocardiography (r3D-echo) was compared to "plain" echocardiographic investigations and was compared to invasive measurements with conduction catheter. CMP significantly attenuated LV dilatation and reduced LV function decline on day 14, as obtained with all echocardiographic modalities and confirmed with conduction catheter measurements. In contrast to plain echocardiography and invasive testing, r3D-echo allowed noninvasive quantification of scar size and assessment of regional contractile reserve. Cell transplanted hearts demonstrated a significant decrease of akinetic myocardial mass (-CMP: 13 ± 2%; +CMP 7 ± 1%; p < 0.001) and increased regional contractile reserve, an indirect sign of myocardial viability. The present study demonstrates beneficial effects of CMP on global and regional parameters of LVR and contractile reserve after MI. In contrast to "simple" 2D echocardiography, r3D-echo allowed the assessment of regional contractile reserve and quantification of akinetic myocardial mass as additive functional and morphological measures of LVR.