Background Treatment of ischemic heart disease remains an important challenge,though there have been enormousprogresses in cardiovascular therapeutics.This study was conducted to evaluate whether Tongxinluo(TXL)treatmentaround the transplantation of mesenchymal stem cells(MSCs)can improve survival and subsequent activities ofimplanted cells in swine hearts with acute myocardial infarction(AMI)and reperfusion.Methods Twenty-eight Chinese mini-pigs were divided into four groups including a control group(n=7);group 2,administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation(n=7);group 3,MSCs alone(n=7)and group 4,TXL+MSCs(n=7).AMI models were made by occlusion of the left anterior descendingcoronary artery for 90 minutes.Autologous bone marrow-MSCs(3×10~7 cells/animal)were then injected into thepost-infarct myocardium immediately after AMI and reperfusion.The survival and differentiation of implanted cells in vivowere detected by immunofluorescent analysis.The data of cardiac function were obtained at baseline(1 week aftertransplantation)and endpoint(6 weeks after transplantation)by single photon emission computed tomography(SPECT)and magnetic resonance imaging(MRI).Apoptosis was detected by TUNEL assay and the oxidative stress level wasinvestigated in the post-infarct myocardium at endpoint.Results At endpoint,there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4than in the control group.In group 4 the survival and differentiation of implanted MSCs were significantly improved morethan that seen in group 3 alone(P<0.0001);the capillary density was also significantly greater than in the control group,group 2 or 3 both in the infarcted zone(P<0.0001)and the peri-infarct zone(P<0.0001).MRI showed that parameters atbaseline were not significantly different between the 4 groups.At endpoint,regional wall thickening and the left ventricularejection fraction were increased while the left ventricular mass index,dyskinetic segments and infarcted size weredecreased only in group 4 compared with control group(P<0.0001).SPECT showed that the area of perfusion defectwas significantly decreased at endpoint only in group 4 compared with control group(P<0.0001).TUNEL assay indicatedthat TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4.Furthermore,superoxide dismutase(SOD)significantly increased and malondialdehyde(MDA)decreased in groups 2 and 4 by theadministration of TXL.Conclusions Our study demonstrates the following:(1)immediate intramyocardial injection of MSCs after AMI andreperfusion resulted in limited survival and differentiation potential of implanted cells in vivo,thus being incapable ofbeneficially affecting post-hearts;(2)TXL-facilitation resulted in a significant survival and differentiation potential ofimplanted cells in vivo via inhibition of apoptosis and oxidative stress,accompanied by significant benefits in cardiacfunction.Chin Med J 2007;120(16):1416-1425 Background Treatment of ischemic heart disease remains an important challenge,though there have been huge advanceds in cardiovascular therapeutics.This study was carried out to evaluate whether Tongxinluo(TXL)treatmentaround the transplantation of mesenchymal stem cells(MSCs)can improve survival and subsequent activities ofimplanted cells in Swine hearts with acute myocardial infarction (AMI) and reperfusion.Methods Twenty-eight Chinese mini-pigs were divided into four groups including a control group(n=7);group 2,administration of low-dose TXL alone from the 3rd day prior To AMI to the 4th day post transplantation(n=7);group 3,MSCs alone(n=7)and group 4,TXL+MSCs(n=7).AMI models were made by occlusion of the left anterior descendingcoronary artery for 90 minutes.Autologous bone marrow-MSCs(3×10~7 cells/animal)were then injected into the post-infarct myocardium immediately after AMI and reperfusion.The survival and differentiation of implanted cells in vivowere detected by immunofluores Cent analysis.The data of cardiac function was obtained at baseline(1 week aftertransplantation)and endpoint(6 weeks after transplantation)by single photon emission computed tomography(SPECT) and magnetic resonance imaging(MRI).Apoptosis was detected by TUNEL assay and the Oxidative stress level was investigated in the post-infarct myocardium at endpoint.Results At endpoint,the was was fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4than in the control group.In group 4 the survival and differentiation of implanted MSCs were significantly improved Morethan that seen in group 3 alone(P<0.0001);the capillary density was also greater greater than in the control group,group 2 or 3 both in the infarcted zone(P<0.0001) and the peri-infarct zone(P<0.0001 ).MRI showed that parameters atbaseline were not significantly different between the 4 groups.At endpoint,regional wall thickening and the left ventricularejection fraction were increased while the leFt ventricular mass index, dyskinetic segments and infarcted size weredecreased only in group 4 compared with control group (P<0.0001). SPECT showed that the area of ​​perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P<0.0001) .TUNEL assay indicatedthat TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4.Furthermore,superoxide dismutase(SOD)significantly increased and malondialdehyde(MDA)decreased in groups 2 and 4 by the administration of TXL.Conclusions. The following:(1)immediate intramyocardial injection of MSCs after AMI and reperfusion results in limited survival and differentiation potential of implanted cells in vivo,thus being incapableficially affecting post-hearts; (2)TXL-facilitation resulted in a significant survival and differentiation potential Ofimplanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanying by significant benef Its in cardiac function.Chin Med J 2007;120(16):1416-1425