Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction.

BACKGROUND: The infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, effectiveness of intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients with AMI still remains unclear. METHODS: Sixty-nine patients with AMI after percutaneous coronary intervention (PCI) were randomly divided into intracoronary injection of BMSCs (n = 34) and saline (control group, n = 35) groups. Serial single positron emission computer tomography (SPECT), cardiac echo and cardiac electromechanical mapping were done at the designed time intervals until six months after transplantation of BMSCs or injection of saline. RESULTS: The proportion with functional defect decreased significantly in the BMSCs patients after three months [(13 +/- 5)%] compared with that pre-transplantation [(32 +/- 11)%] and the control group [(28 +/- 10)%] at three month follow-up (P < 0.05, respectively). Wall movement velocity over the infracted region increased significantly in the BMSCs group [(4.2 +/- 2.5) cm/s vs (2.2 +/- 1.3) cm/s, P < 0.05], but not in the control group [(2.2 +/- 1.5) cm/s vs (2.7 +/- 1.7) cm/s, P > 0.05]. Left ventricular ejection fraction (LVEF) three months after transplantation in BMSCs group increased significantly compared with that pre-implantation and with that of the control group at three months post-injection [(67 +/- 11)% vs (49 +/- 9)% and (53 +/- 8)%, P < 0.05 respectively]. SPECT scan results showed that perfusion defect was improved significantly in BMSCs group at three-month follow-up compared with that in the control group [(134 +/- 66) cm(2) vs (185 +/- 87) cm(2), P < 0.01]. At the same time, left ventricular end-diastolic volume [(136 +/- 31) ml vs (162 +/- 27) ml, P < 0.05] and end-systolic volume [(63 +/- 20) ml vs (88 +/- 19) ml, P < 0.05] decreased synchronously. The ratio of end-systolic pressure to end-systolic volume [Psyst/ESV, (2.84 +/- 1.30) mmHg/ml vs (1.72 +/- 1.23) mmHg/ml, P < 0.05] increased significantly. Cardiac electromechanical mapping demonstrated significant improvement at three months after implantation of BMSCs compared with that pre-injection in both cardiac mechanical capability as left line local shorting [LLS, (11.29 +/- 1.64)% vs (7.32 +/- 1.86)%, P < 0.05] and electrical property as left ventricular endocardial unipolar voltage [UV, (10.38 +/- 1.12) mV vs (7.61 +/- 1.09) mV, P < 0.01]; perfusion defect decreased from (36.2 +/- 6.2)% to (20.3 +/- 5.31)% (P < 0.01). Twenty-four-hour electrocardiographic monitoring demonstrated no arrhythmias occurred at three-months follow-up. CONCLUSIONS: The transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias.

Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction.

Sixty-nine patients who underwent primary percutaneous coronary intervention within 12 hours after onset of acute myocardial infarction were randomized to receive intracoronary injection of autologous bone marrow mesenchymal stem cell or standard saline. Several imagining techniques demonstrated that bone marrow mesenchymal stem cells significantly improved left ventricular function.

Alteration of endothelin system and calcium handling protein in left ventricles following drug treatment in dilated cardiomyopathy rats.

AIM: To investigate the changes of cardiac calcium handling proteins and endothelin system in dilated cardiomyopathy (DCM) rats and the effects of perindopril and bisoprolol on the remodeling ventricles. METHODS: DCM rats were employed using a 2-kidney, 1-clip hypertensive and diabetic model. Some of the DCM rats were treated with perindopril and bisoprolol for 3 months, respectively. The ratio of left ventricular weight to body weight (LVW/BW), mRNA expressions of calcium handling proteins and endothelin receptors were determined. The alterations of maximum binding capacity (Bmax) and equilibrium dissociation constant (KD) values of cardiac endothelin receptors (ETR) and its subtypes were detected. RESULTS: Compared with those of normal control, blood pressure, and LVW/BW in the DCM rats were elevated. Sarcoplasmic reticulum calcium pump (SERCA) mRNA expression and SERCA activity decreased in the left ventricle. The ETR Bmax decreased, especially the endothelin receptor A. Endothelin converting enzyme activity and expression were elevated, and mRNA expressions of beta1-adrenoreceptor and inositol-3-phosphate receptor in some hearts increased as well. The administration of perindopril and bisoprolol could reverse myocardial hypertrophy and restore the imbalance of calcium handling proteins and endothelin system. CONCLUSION: The disorder of calcium handling proteins and endothelin system existed in the hearts of DCM rats. Treatment of perindopril and bisoprolol could reverse myocardial hypertrophy and changes in DCM rats.