Objective To investigate the effect of combined delivery of hepatocyte growth factor (HGF) and insulinlike growth factor-1 (IGF-1) on the development of bone mesenchymal stem cells (BMSCs) differentiation by expression of GATA-4，and to supply some evidence for clinical BMSCs transplantation therapy. Methods BMSCs were isolated from the femurs and tibias of the randomly assigned rabbits and cocultured with myocytes in a ratio of 1∶1. Myocytes were obtained from neonatal rabbits ventricles. 150 ng/ml HGF and 200 ng/ml IGF-1 were added into 4 culture bottles of 8 bottles and the other 4 bottles were not. After BMSCs were cocultured with myocytes for 1 day, 3 days, 1 week, and till 6 weeks， differentiated BMSCs were targeted and microdissected with a laser capture microdissection system, and then ribonucleic acid (RNA) was extracted and isolated. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcriptionpolymerase chain reaction (RT-PCR). And expression of GATA-4 in BMSCs was detected by semiquantitative RT-PCR. Results Before coculturing, the BMSCs were negative for α-actinin and exhibited a nucleus with many nucleoli. After coculture with myocytes, some BMSCs became αactininpositive and showed a cardiomyocytelike ultrastructure, including sarcomeres, endoplasmic reticulum, and mitochondria. BMSCs cocultured with myocytes expressed cardiac transcription factor GATA-4. IGF-1 and HGF delivery can significantly increased expression of GATA-4 for the differentiated BMSCs as compared with cells of no delivery of HGF and IGF-1. The expression level of GATA-4 in captured BMSCs began to increase at the 1st day, reach the peak at the 2nd week and kept high expression level after the 2nd week. Conclusion BMSCs can transdifferentiate into cells with a cardiac phenotype when cocultured with myocytes. Differentiated myocytes express cardiac transcription factors GATA-4. Administration of HGF and IGF-1 promoted the development of BMSCs transdifferentiate into cardiac phenotype, which is associated with the increase in expression level of GATA-4.
Abstract:Objective To investigate the expression and significance of Voltage-gated Cl channel-3 （ClC-3） in acute cardiac allograft rejection in rats. Methods The model of heterotopic cardiac allograft of SD to Wistar rats was established. The rats were divided into two groups： control group and cyclosporin A（CsA） treated group （CsA group）. Living span of the transplants in eight rats of each group were observed. Allograft samples were harvested separately on the day 1, 3, 5, 7 after operation （n = 6）. The rejection was evaluated by routine pathological examinations. The myocardial apoptosis by terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling （TUNEL） method and the local expression of ClC-3 were detected by reverse transcriptase polymerase chain reaction （RT-PCR）. Results The allografts survival time was significantly longer in CsA group compared with that in control group （15.4±5.1dvs. 7.6±1.5d, P〈0.05）. There was lesser pathological changes in CsA group than that in control group. The apoptosis index were significantly higher in control group and the expression of ClC-3 was significantly lower（P〈0.05）. CsA could inhibit the rise of apoptosis index and the decrease of the ClC-3 expression. Conclusion The ClC-3 expression is closely related with the severity of myocardial necrosis and apoptosis index, which indicates that ClC-3 plays a very important role in the necrosis and apoptosis during acute cardiac allograft rejection of rat.
Objective To observe the influence of edaravone perfusion via the pulmonary artery on postoperative lung tissue and lung function during pulmonary ischemia in deep hypothermic circulatory arrest （DHCA）， and explore its possible mechanism. Methods A total of 24 healthy New Zealand white big-ear rabbits were randomly divided into three groups： （1） control group： DHCA model under cardiopulmonary bypass （CPB） was established； （2）low potassium dextran （LPD）group： LPD solution perfusion via the pulmonary artery after the establishment of DHCA； （3）edaravone group：LPD solution containing edaravone （5 mg/kg） perfusion via the pulmonary artery after the establishment of DHCA. Oxygenation index and lung compliance were observed at the time of baseline condition， recovery of ventilation， 1 hour and 2 hours after recovery of ventilation， and postoperative lung function of the three groups were compared. Malondialdehyde （MDA） and superoxide dismutase （SOD） in pulmonary venous blood were measured. All the rabbits were sacrificed after the operation. HE staining and immunohistochemistry were performed on the lung tissues to investigate lung structure changes and inflammatory reaction. Transmission electron microscopy was used to compare ultrastructural changes of lung.Results There were no statistical difference in oxygenation index， lung compliance， MDA and SOD among the 3 groups under the baseline condition （P＞0.05）. After recovery of ventilation， oxygenation index and lung compliance deteriorated to varying degrees in all 3 groups. Oxygenation index and lung compliance of the control group and LPD group at the time of recovery of ventilation， 1 hour and 2 hours after recovery of ventilation were significantly lower than those of edaravone group （oxygenation index：recovery of ventilation and in control group and edaravone group: 198.25±11.02 mm Hg vs. 244.87±13.05 mm Hg；lung compliance：one hour after recovery ventilation in control group and edaravone group：45.88±1.64 ml/cm H2O vs. 59.75±2.38 ml/cm H2O；P＜0.05）. After CPB removal， MDA levels were increased to varying degrees in all 3 groups. MDA levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly higher than those of edaravone group （P＜0.05）. After CPB removal， SOD levels were decreased to varying degrees in all 3 groups. SOD levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly lower than those of edaravone group （P＜0.05）. HE staining showed clear lung structure， less red blood cell leakage， less inflammatory cell infiltration， and less alveolar fluid accumulation in the edaravone group. Immunohistochemistry showed that integral light density of interleukin 6 （IL-6）in edaravone group was significantly lower than those of the LPD group and control group （14.44±1.75 vs. 20.18±2.22， P＜0.05）. Transmission electron microscopy showed integral basement membrane structure， clear blood gas barrier structure， significantly larger number of type II epithelial cells， abundant but not swollen mitochondria and lamellar bodies in the cytoplasm in the edaravone group， which were destroyed in varying degrees in the LPD group and control group. Conclusion Pulmonary artery perfusion of protective solution in low temperature can significantly reduce lung injury induced by DHCA and CPB. Protective solution containing edaravone in low temperature can better decrease lung injury and protect oxygenation.
Objective To compare the clinical outcomes and safety of minimally invasive and routine mitral valve repair or replacement for patients with single mitral valve disease. Methods We retrospectively analyzed the clinical data of 67 patients with single mitral valve disease （without aortic valve and tricuspid valve lesion or other heart diseases including atrial septal defect） who underwent mitral valve repair or replacement in the First Affiliated Hospital of China Medical University between January and July 2011. The patients were divided into two groups according to different surgical approaches：the minimally invasive surgery group （n=29，8 males and 21 females，age 51.4±9.4 years） underwent minimally invasive mitral valve repair or replacement via right mini-thoractomy；and the routine surgery group （n=38，11 males and 27 females，age 53.6±11.9 years） underwent mitral valve repair or replacement via middle sternotomy. In the minimally invasive surgery group，9 patients underwent mitral valve repair while the other 20 patients underwent mitral valve replacement. And no patient underwent transition to routine operation. In the routine surgery group，15 patients underwent mitral valve repair and 23 patients underwent mitral valve replacement. Clinical outcomes and safety of the operations were compared between the two groups. Results There was no statistical difference in operation time between the two groups （207.9±18.1 min versus 198.4±27.5 min，P=0.076）. The amount of postoperative drainage （126.7±34.5 ml versus 435.6±87.2 ml，P=0.000） and blood transfusion （red blood cell 1.4±0.8 U versus 2.3±1.1 U，P=0.000；blood plasma 164.3±50.4 ml versus 405.6±68.9 ml，P=0.000） of the minimally invasive surgery group were significantly lower than those of the routine surgery group. The cardiopulmonary bypass time （81.7±23.9 min versus 58.7±13.6 min，P=0.000） and aortic-clamping time （51.6±12.7 min versus 38.4±11.7 min，P=0.000） of the minimally invasive surgery group were significantly longer than those of the routine surgery group. The length of ICU stay （22.5±3.6 h versus 31.7±8.5 h，P=0.000），mechanical ventilation （7.4±3.2 h versus 11.2±5.1 h，P=0.000） and postoperative hospitalization （7.1±1.6 d versus 13.5±2.4 d，P=0.000） of the minimally invasive surgery group were significantly shorter than those of the routine surgery group. There was no statistical difference in postoperative complications between the two groups. Minimally invasive surgery group patients were followed up for 5.3±2.4 months with a follow-up rate of 72.4%（21/29）. Routine surgery group patients were followed up for 5.5±3.8 months with a follow-up rate of 71.0%（27/38）. There was no significant complication during follow-up in both two groups. Conclusion Minimally invasive mitral valve operation via right mini-thoracotomy is effective and safe with a good cosmetic result. Compared with routine operation，patients undergoing minimally invasive operation recover better and faster.
Objective To investigate the impact of preoperative use of low-molecular-weight heparin （LMWH） on early outcomes of off-pump coronary artery bypass grafting （OPCAB） . Methods Clinical data of 809 patients undergoingisolated OPCAB from April 1st，2011 to September 30th，2012 in the First Affiliated Hospital of China Medical University were retrospectively analyzed. All the patients were divided into LMWH group and control group according to preoperative use of LMWH or not. In LMWH group，there were 386 patients including 290 male and 96 female patients with their age of 49-81 years，who routinely received anticoagulation therapy with LMWH （LMWH sodium or LMWH calcium，4 000 U twice a day，subcutaneous injection） after discontinuation of anti-platelet therapy until the day before surgery. In the control group，there were 423 patients including 321 male and 102 female patients with their age of 46-78 years，who didn’t receive LMWH or any other anticoagulant after discontinuation of anti-platelet therapy. Postoperative mortality，incidence of perioperative myocardial infarction （MI），operation time，amount of blood loss and transfusion，and incidence of postoperative acute renal injury were compared between the 2 groups. Results Intraoperative blood loss （296±94 ml vs. 249±81 ml，P=0.03），postoperative thoracic drainage （526±159 ml vs. 410±125 ml，P=0.02），blood transfusion （2.6±1.1 U vs. 1.4±0.9 U，P=0.04） and operation time （172±34 min vs. 154±41 min，P=0.04） of LMWH group were significantly larger or longer than those of the control group. There was no statistical difference in postoperative mortality（1.0% vs. 1.2%，P=1.00）or incidence of perioperative MI（4.4% vs. 3.8%，P=0.55）between the 2 groups. Conclusion For OPCAB patientswith stable ischemic heart disease，preoperative management without use of LMWH can decrease operation time and amountof blood loss and transfusion without increasing postoperative mortality or incidence of perioperative MI.
ObjectiveTo explore the effect of skeletonized left internal mammary artery (LIMA) in coronary artery bypass grafting (CABG). MethodsA total of 122 patients who underwent pure CABG were recruited in the study in the First Affiliated Hospital of China Medical University between January and April 2013. There were 77 males and 45 females with age of 41-76(62.8±10.5) years. They were randomly assigned to received CABG with skeletonized LIMAs (group A, 60 patients) or pedicle LIMAs (the group B, 62 patients) by random digital table. LIMAs were all anastomosised to the left anterior descending artery. ResultsThere was one patient failure in harvesting LIMA process in the group A and B respectively, and they were changed to saphenous vein grafts and excluded from the criteria. There were 2 and 3 patients of postoperative myocardial infarction in the group A and in the group B respectively, with incidence rate of 3.4% and 4.9% respectively (P > 0.05). One patient died in each group during hospitalization with hospital mortality rates of 1.7% and 1.6% respectively (P > 0.05). Complications such as mediastinal infection occurred zero and one patient in the group A and in the group B respectively (P > 0.05). LIMA harvesting time of the group A was statistically longer than that of the group B (30.7±7.2 min vs. 17.2±5.6 min, P < 0.05). In six months of follow-up after surgery, coronary CT showed patency rate of LIMA in the group A and in the group B was 96.8% and 100.0% respectively (P > 0.05). ConclusionThe recent effect of skeletonized LIMA as graft material in CABG is satisfactory.
Objective To study the technical characteristics, clinical outcomes and short- and long-term results of minimally invasive multi-vessel coronary artery bypass grafting and to evaluate the feasibility and efficacy. Methods From April 2012 to December 2014, minimally invasive cardiac surgery for coronary artery bypass grafting (MICS CABG) in 11 patients was performed in the First Hospital of China Medical University. All patients were males and the average age was 62.7 (47.0-73.0) years. Eight patients with 3-vessel lesions and 3 patients with 2-vessel lesions. General anesthesia was performed with double lumen endotracheal intubation and single lung ventilation. The patient was positioned 15 degrees to 30 degrees in right lateral position. The left anterior and lateral incision was made at the fourth/fifth intercostal space with the length of 5-7 cm and 2/3 part of the incision located in the medial side of anterior axillary line. Left internal thoracic artery (LIMA) was harvested from the third intercostal space up to the subclavian vein and down to more than fifth intercostal space through the surgical window. Through the xiphoid and sixth intercostal space incision with the length of 1 cm, the Starfish and Octopus system were placed to fix apex and ascending aorta and target vessels were exposed. The proximal and distal anastomosis was done under the direct vision. The sequence of distal anastomosis was from posterior descending branch to obtuse/diagonal branch and left anterior descending branch. The chest and pericardial draining tubes were placed through the xiphoid and sixth intercostal space incision. Results The mean operation time was 4.1 (3.2–5.8) h. Five patients underwent the operation with the assist of cardiopulmonary bypass and the mean assisting time was 21.0 (17.0-38.0 ) min. The mean number of distal anastomosis was 2.8 (2.0-3.0) and LIMA was harvested and grafted in all 11 patients. The mean drainage was 425.0 (180.0-750.0) ml, mean ventilation time 7.8 (4.3-11.2) h, ICU stay 15.9 (11.0-38.0) h, and hospital time 7.7 (5.0-14.0) d. There was no operative death and re-exploration for bleeding. One patient was complicated by paroxysmal atrial fibrillation and one patient myocardial infarction. The average follow-up was 19.4 (12.0-36.0) months, and no chest pain, re-admission or re-intervention happened. Coronary artery CT angiographies demonstrated that all LIMAs were patent and 4 vein grafts were occluded and venous graft patency rate was 80.0% one year after surgery. Conclusion MICS CABG has the advantage of quick recovery, good cosmetic effect and low incision infection rate compared to the conventional CABG. Compared with robotic surgery, the cost of MICS CABG is low and the same as that of the conventional CABG. It is a new kind of CABG and could be performed following the learning curve under strict training of doctors and careful patient selection. With the good short- and middle-term results, MICS CABG needs to be evaluated for long-term graft patency rate, re-revascularization rate, and clinical evidence.
ObjectiveTo summarize clinical experience of different surgical strategies for the treatment of acute Stanford type A aortic dissection (AD). MethodsClinical data of 197 patients with acute Stanford type A AD who underwent surgical treatment in the First Affiliated Hospital of China Medical University from January 2008 to November 2012 were retrospectively reviewed. There were 131 males and 66 females with their age of 24-77 (51.2±13.9) years. All the patients received magentic resonance imaging (MRI) or aortic CT angiography (CTA) for the establishment of diagnosis. According to different aortic root conditions,ascending aorta replacement,Bentall,Wheat,Cabrol or David procedures were performed. Total arch replacement, hemiarch replacement or simplified total arch replacement was also performed for aortic arch dissection combined with stented elephant trunk implantation. ResultsA total of 113 patients (57.4%) underwent isolated ascending aorta replacement,67 patients (34.0%) received Bentall procedure,13 patients (6.6%) received Wheat procedure,1 patient(0.5%) received Cabrol procedure,and 3 patients (1.5%) received David procedure. Eighty-two patients (41.6%) underwent total arch replacement combined with stented elephant trunk implantation,77 patients (39.1%) received hemiarch replacement, and the other 41 patients (20.8%) received simplified total arch replacement combined with stented elephant trunk implantation. One patient (0.5%) underwent reexploration for postoperative bleeding. No permanent neurological complication occurred. Thirty-day mortality after surgery was 4.1% (8/197). Follow-up duration was 3-52 (15.9±11.4) months with the follow-up rate of 65.0%. One patient with Marfan syndrome died of abdominal aortic aneurysm rupture 8 months after surgery. ConclusionAccording to different AD conditions, appropriate surgical strategies can be chosen to achieve satisfactory clinical outcomes for patients with acute Stanford type A AD.