Cellular cardiomyoplasty with bone marrow mesenchymal stem cells and ramipril improves cardiac performance induced by infarct in rabbits

Objective This study assessed whether a synergic effect is manifested in two treatment modalities of induced bone marrow mesenchymal stem cells(MSCs)transplantation and ramipril improved cardiac performance after myocardial infarction(MI)in rabbits.Methods MI was created in 40 New Zealand white rabbits by the left anterior descending coronary artery ligation.They were divided into 4 groups.Two groups did not receive any drug and were intramyocardially injected 2 weeks after the infarction with either culture medium alone (group 1,n=7)or 5-azacytidine(5-aza)induced MSCs(group 2,n=7).Two other groups received the ACE inhibitor (ACEI)ramipril(1 mg·kg -1·d -1),started the day of the infarction and continued uninterruptedly thereafter,and underwent time-matched procedures,that is,they were intramyocardially injected at 2 weeks after infarction with either freeserum culture medium alone(group 3,n=8),or autologous 5-aza-induced MSCs(group 4,n=7).Left ventricular function was assessed by echocardiography at 8 weeks after MI.A fluid-filled catheter was introduced into the carotid and left ventricular end-diastolic pressure (LVEDP)were analyzed. Results At the end of the 8 weeks study,left ventricular ejection fraction(LVEF)was increased in all groups(group 2:38 1%±4 8%?3:36 4%±4 3%?4:47 3%±5 9%)compared with that in group 1(22 7%±5 5%)(P0 05).The improvement in LVEF was similar in the group 2 and 3.However,in the group 4 this improvement was greater than that seen in hearts receiving either treatment alone(P0 05).Myocardial systolic velocity of anterior and anteroseptal wall significantly increase in the group 2 and 4 compared with group 1 and 3.LVEDP significantly decreased in the group 2,3 and 4.Conclusion These data provide support for the clinical relevance of 5-aza induced MSCs transplantation in that its cardioprotective effects are additive to those observed with ACEI.