Echocardiographic evaluation of the effects of stem cell therapy on perfusion and function in ischemic cardiomyopathy

Abstract

Background: Small animal models of ischemic left ventricular (LV) dysfunction are important for the preclinical optimization of stem cell therapy. The aim of this study was to test the hypothesis that temporal changes in LV function and regional perfusion after cell therapy can be assessed in mice using echocardiographic imaging.

Methods: Wild-type mice (n = 25) were studied 7 and 28 days after permanent ligation of the left anterior descending coronary artery. Animals were randomized to receive closed-chest ultrasound-guided intramyocardial delivery of saline (n = 13) or 5 × 10(5) multipotential adult progenitor cells (MAPCs; n = 12) on day 7. LV end-diastolic and end-systolic volumes, LV ejection fraction, and stroke volume were measured using high-frequency echocardiography. Multiplanar assessments of perfusion and defect area size were made using myocardial contrast echocardiography.

Results: Between days 7 and 28, MAPC-treated animals had 40% to 50% reductions in defect size (P < .001) and 20% to 30% increases in total perfusion (P < .01). Perfusion did not change in nontreated controls. Both LV end-diastolic and end-systolic volumes increased between days 7 and 28 in both groups, but LV end-systolic volume increased to a lesser degree in MAPC-treated compared with control mice (+4.2 ± 7.9 vs +19.2 ± 22.0 μL, P < .05). LV ejection fraction increased in the MAPC-treated mice and decreased in control mice (+3.0 ± 4.3% vs -5.6 ± 5.9%, P < .01). There was a significant linear relation between the change in LV ejection fraction and the change in either defect area size or total perfusion.

Conclusions: High-frequency echocardiography and myocardial contrast echocardiography in murine models of ischemic LV dysfunction can be used to assess the response to stem cell therapy and to characterize the relationship among spatial flow, ventricular function, and ventricular remodeling.

Keywords: Contrast echocardiography; Echocardiography; LAD; LV; LVEDV; LVEF; LVESV; Left anterior descending coronary artery; Left ventricular; Left ventricular ejection fraction; Left ventricular end-diastolic volume; Left ventricular end-systolic volume; MAPC; MCE; Microbubbles; Multipotential adult progenitor cell; Myocardial contrast echocardiography; Stem cells.