Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>The transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias.</p>

Analysis of endothelin receptor and its subtypes in the left ventricle of rats with dilated cardiomyopathy / 中国临床药理学与治疗学

Aim To observe the changes of endothelin receptors and their subtypes of left ventricules in normal SD rats and dilated cardiomyopathy rats. Methods To establish the best conditions of the binding experiment, different protein concentrations, incubation temperature ?and?incubating?time?were?tested? with 125 I-ET-1 ligand respectively. With the selected conditions, saturation binding experiments were performed to determine the amount of endothelin receptor and its subtypes in normal SD rats and in dilated cardiomyopathy ones. Results (1) The optimal incubating temperature was 37 ℃. Under this condition, the binding amount of 125 I-ET-1 increased rapidly in 0～30 minutes, and reached to saturation point at 60 minutes, and there was a linear correlation between 125 I-ET-1 binding amount and cell membrane protein concentration. (2) Endothelin-1, bosentan,BQ123,BQ788 etc. could competitively suppress the bound of 125 I-ET-1 to endothelin receptors. (3) The amount of endothelin receptor in left ventricle of dilated cardiomyopathy rats was ( 92.21? 34.34) nmol?kg -1 protein, which was significantly low than that in normal SD ones. There was no change on the ratio of endothelin receptor subtypes A and B. Conclusion 125I-ET-1 can be used to determine the amount of endothelin receptor and its subtypes in varied tissues specifically. The amount of endothelin receptor in left ventricle of dilated cardiomyopathy rats is down regulated, but the ratio of endothelin receptor subtype A vs B remains to be 21.