Echocardiographic Evaluation of the Effects of Stem Cell Therapy on Perfusion and Function in Ischemic Cardiomyopathy
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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聽=聽25) were studied 7 and 28聽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聽=聽13) or 5聽脳聽105 multipotential adult progenitor cells (MAPCs; n聽=聽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聽<聽.001) and 20% to 30% increases in total perfusion (P聽<聽.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聽卤聽7.9 vs +19.2聽卤聽22.0聽渭L, P聽<聽.05). LV ejection fraction increased in the MAPC-treated mice and decreased in control mice (+3.0聽卤聽4.3% vs 鈭?.6聽卤聽5.9%, P聽<聽.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.

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