W Streb

Differential Effects of Progenitor Cell Populations on Left Ventricular Remodeling and Myocardial Neovascularization After Myocardial Infarction

OBJECTIVES We compared biological repair after acute myocardial infarction (AMI) with selected porcine progenitor cell populations. BACKGROUND Cell types and mechanisms responsible for myocardial repair after AMI remain uncertain. METHODS In a blinded, randomized study, we infused autologous late-outgrowth endothelial progenitor cells (EPC) (n = 10, 34 +/- 22 x 10(6) CD29-31-positive, capable of tube formation), allogeneic green fluorescent peptide-labeled mesenchymal stem cells (MSC) (n = 11, 10 +/- 2 x 10(6) CD29-44-90-positive, capable of adipogenic and osteogenic differentiation), or vehicle (CON) (n = 12) in the circumflex artery 1 week after AMI. Systolic function (ejection fraction), left ventricular (LV) end-diastolic and end-systolic volumes, and infarct size were assessed with magnetic resonance imaging at 1 week and 7 weeks. Cell engraftment and vascular density were evaluated on postmortem sections. RESULTS Recovery of LV ejection fraction from 1 to 7 weeks was similar between groups, but LV remodeling markedly differed with a greater increase of LV end-systolic volume in MSC and CON (+11 +/- 12 ml/m(2) and +7 +/- 8 ml/m(2) vs. -3 +/- 11 ml/m(2) in EPC, respectively, p = 0.04), and a similar trend was noted for LV end-diastolic volume (p = 0.09). After EPC, infarct size decreased more in segments with >50% infarct transmurality (p = 0.02 vs. MSC and CON) and was associated with a greater vascular density (p = 0.01). Late outgrowth EPCs secrete higher levels of the pro-angiogenic placental growth factor (733 [277 to 1,214] pg/10(6) vs. 59 [34 to 88] pg/10(6) cells in MSC, p = 0.03) and incorporate in neovessels in vivo. CONCLUSIONS Infusion of late-outgrowth EPCs after AMI improves myocardial infarction remodeling via enhanced neovascularization but does not mediate cardiomyogenesis. Endothelial progenitor cell transfer might hold promise for heart failure prevention via pro-angiogenic or paracrine matrix-modulating effects.

The quantification of dipyridamole induced changes in regional deformation in normal, stunned or infarcted myocardium as measured by strain and strain rate: an experimental study.

Strain rate imaging (SRI) during dobutamine stress-echocardiography (DSE) has been shown to differentiate between ischemic substrates based on the segmental response. Dipyridamole stress echo (DIPSE) is currently used as an alternative to DSE in detecting coronary artery disease. The aim of this study was: (a) to determine the normal response in peak-systolic myocardial strain (S) and strain-rate (SR) during DIPSE and (b) to compare the S and SR responses of DSE and DIPSE in the same chronically ischemic/infarcted segments in the setting of single vessel disease. Methods The deformation response to DIPSE was studied in 7 normal pigs and in an additional 18 pigs, with a spectrum of ischemic substrates. S and SR data were extracted from a posterior wall “at risk” segment at baseline and during both DSE and DIPSE. The animals were divided into different ischemic substrate (stunning, non-transmural and transmural infarction), based on the DSE response as previously suggested. Results In normal myocardium, dipyridamole induced no changes in regional systolic deformation neither during nor after the infusion. Furthermore there was no detectable response in S and SR in segments with either a non-transmural or a transmural infarction. However, in myocardial segments with a DSE “stunning response”, both end systolic S and peak-systolic SR tended to “normalize” at peak dipyridamole dose. Conclusions These results suggest that dipyridamole does not induce changes in regional deformation in normal or (partially) infarcted myocardium. Only in stunned myocardium (in the setting of single-vessel disease), dipyridamole tends to normalize deformation.