National Primary Care Day \u2797

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Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy

ObjectivesIn a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling.MethodsSprague–Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28.ResultsInjection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean ± standard deviation: maximum dP/dt 3048 ± 230 mm Hg/s vs 2169 ± 97 mm Hg/s at 21 days and 3573 ± 741 mm Hg/s vs 1363 ± 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 ± 35 seconds vs 306 ± 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor–alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days.ConclusionsIn this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload

Predictive effect of determinants of health on prevalence of diseases in India. An approach for measurement in a multi-factorial and multi-level setting.

The burden of acute and chronic diseases in India is higher than their respective global averages. To mitigate this in an effective and resource efficient way, the concerned health policy should undertake interventions against the determinants that can predict the prevalence of acute and chronic diseases in a multi-factorial setting. In addition, the policy should be customized at appropriate administrative levels to account for the variation attributed to the local context. To identify the appropriate determinants for intervention, and administrative levels for customization, data on 17 determinants from 274 district nested within 21 states was used, and analyzed using a combination of multiple regression analysis and multi-level analysis techniques. Consequently, 8 determinants were identified to have predictive ability on prevalence of acute diseases, while prevalence of chronic disease could be predicted by 10 determinants. State level was identified as the appropriate level for customization of the policies concerned with all the predictive determinants, while district level was identified as the appropriate level for customization for only half of the predictive determinants

Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy

Changes in ventricular extracellular matrix (ECM) composition of pressure overload hypertrophy determine clinical outcomes. The effects of mesenchymal stem cell (MSC) transplantation upon determinants of ECM composition in pressure overload hypertrophy have not been studied. Sprague–Dawley rats underwent aortic banding and were followed by echocardiography. After an absolute decrease in fractional shortening of 25% from baseline, 1 × 10 6 MSC ( n = 28) or PBS ( n = 20) was randomly injected intracoronarily. LV protein analysis, including matrix metalloproteinases (MMP-2, MMP-3, MMP-6, MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3), was performed after sacrifice on postoperative day 7, 14, 21 or 28. Left ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 were demonstrated to be decreased in the MSC group compared with controls after 28 days. Expression of MMP-2 and TIMP-2 remained relatively stable in both groups. Successful MSCs delivery was confirmed by histological analysis and visualization of labelled MSCs. In this model of pressure overload hypertrophy, intracoronary delivery of MSCs during heart failure was associated with specific changes in determinants of ECM composition. LV reverse remodeling was associated with decreased ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3, which were upregulated in the control group as heart failure progressed. These effects were most significant at 28 days following injection. Copyright © 2008 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61900/1/137_ftp.pd