(LVIDs, Fig. 6b). Transplantation of CPCs significantly attenuated the cardiac remodeling, yielding a smaller, 21%, increase of the LVIDd (2.8860.1 mm to 3.560.18 mm) and a 53% increase of the LVIDs (1.4760.07 mm to 2.2660.27 mm). Over the span of 4 weeks the ejection fraction (EF, Fig. 6c) in the control group (saline-injected infracted animals) de- creased from 76.866.9% to 38.0610%, while for the CPC- treated infracted animal group there was a lesser ejection fraction decrease (79.964% to 63.163%) which was also comparable to that of the sham groups, thus, indicating preserved hemodynamic function. Consistent with these results, fractional shortening (FS) following infarction injury and saline injection was significantly reduced from 44.2964.4% before LAD ligation to 26.0865.07% after 4 weeks. In contrast, CPC injection in the infracted zone preserved the FS (46.0462.32% to 44.6664.5%) at levels measured prior to the infarction injury, and similar to the results obtained for the sham groups (Fig. 6d). Survival. A total of 55 surgical procedures were performed with a surgical mortality of 10.9% (Fig. S2). Forty mice finished the 4 weeks of the study, of which 26 underwent successful hemodynamic analysis with a pressure-volume catheter. Progenitor Cell Heart Therapy Determination of cardiac functional output by pressure- volume analysis In order to further access the cardiac functional capacity of the four animal groups we performed Pressure-Volume loop analysis (Fig. 7) [21]. Consistent with the echocardiographic analysis of ventricular dilatation, the end diastolic volume (EDV, Fig. 7a) for the saline- injected infracted animals measured 49.5610.0 ml, as compared to 29.462.9 ml for the CPC-treated infracted animal group. The animals that underwent sham surgery and received either cells or saline injections measured 20.161.2 ml and 22.561.9 ml respectively. Hemodynamic catheterization also allowed the measurement of the indices of myocardial contractility (Fig. 7b). Peak pressure rise ((dP/dt)max) is a measure of the fastest pressure rise within the left ventricle during the isovolumetric phase of myocardial contraction and it can be correlated with the peak acceleration of blood in the descending aorta through the ventricle. The left ventricular peak pressure rise ((dP/dt)max) for the control group (saline-injected infracted animals, 5830.36584.5 mmHg/sec) was lower than that of the CPC-treated infracted animals (8427.361850.8 mmHg/sec), which in turn was comparable to the ((dP/dt)max) values measured for the saline-treated sham animals (10,373.46649.5 mmHg/sec) but lower than those measured for the cell-treated sham animals (11,826.061433.6 mmHg/sec). Figure 7. Pressure-Volume loop analysis. Left ventricular pressure-volume analysis in the four groups 4 weeks post infarction. The CPC treated group exhibited preservation of ventricular volume in diastole (a) (p,0.01). An improved relaxation constant (Tau-Weiss) is observed in CPC treated mice (c) (p,0.01). (dP/dt)max (b) and preload recruitable stroke work (PRSW) (d) was improved in the CPC treated group exhibiting preserved contractility parameters. (e) Sample Pressure-volume loop recordings from individual mice four weeks after myocardial infarction. While the sham treated mouse has kept its end-diastolic and end-systolic volumes these parameters have increased in MI ones with less maximum pressure, however the degree of dilatation and remodeling seems increased in the saline treated mouse as compared to the one receiving CPCs. doi:10.1371/journal.pone.0011536.g007 PLoS ONE | www.plosone.org 9 July 2010 | Volume 5 | Issue 7 | e11536