Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1alpha activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1alpha. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1alpha expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1alpha was important for MSC survival under hypoxic conditions.

Surgical Treatment of Thoracic Menigocele Associated with Neurofibromatosis and Kyphoscoliosis

A 46-year-old man presented with a lateral thoracic meningocele associated with cutaneous neurofibromatosis type I and kyphoscoliosis of the thoracic spine upon medical examination. In the majority of such cases, these meningoceles remain asymptomatic, but surgery is indicated when giant or symptomatic cysts are present. The large thoracic meningocele was successfully extirpated through the transthoracic approach in combination with lumbar puncture and cerebrospinal drainage for decompression of the cyst.

Thoracic Epidural Anesthesia and Analgesia (TEA) in Patients with Rib Fractures

BACKGROUND: We analyzed the results of surgical reduction and fixation of ribs under thoracic epidural anesthesia and analgesia (TEA) in patients who had no more than 3 consecutive rib fractures with severe displacement to examine the clinical usefulness of this method. MATERIALS AND METHODS: From May 2008 to March 2010, 35 patients underwent surgical reduction and fixation of ribs under TEA. We reviewed the indications for this technique, number of fixed ribs, combined surgical procedures for thoracic trauma, intraoperative cardiopulmonary events, postoperative complications, reestablishment of enteral nutrition, and ambulation. RESULTS: The indications of TEA were malunion or nonunion of fractured ribs in 29 (82.9%; first operation) and incompletely ribs under previous general anesthesia in 6 (17.1%; second operation). The average number of fixed ribs per patient was 1.7 (range: 1~3). As a combined operation for thoracic trauma, 17 patients (48.6%) underwent removal of intrathoracic hematomas, and we performed repair of lung parenchyma (2), wedge resection of lung (1) for accompanying lung injury and pericardiostomy (1) for delayed hemopericardium. No patient had any intraoperative cardiopulmonary event nor did any need to switch to general anesthesia. We experienced 3 postoperative complications (8.6%): 2 extrapleural hematomas that spontaneously resolved without treatment and 1 wound infection treated with secondary closure of the wound. All patients reestablished oral feeding immediately after awakening and resumed walking ambulation the day after operation. CONCLUSION: Thoracic epidural anesthesia and analgesia (TEA) may positively affect cardiopulmonary function in the perioperative period. Moreover, this technique leads to an earlier return of gastrointestinal function and early ambulation without severe postoperative complications, resulting in a shortened hospital stay and lowered costs.

Ideal Freezing Curve Can Avoid the Damage by Latent Heat of Fusion During Freezing / 대한흉부외과학회지

BACKGROUND: Liquid nitrogen freezing techniques have already met with widespread success in biology and medicine as a means of long-term storage for cells and tissues. The use of cryoprotectants such as glycerol and dimethylsulphoxide to prevent ice crystal formation, with carefully controlled rates of freezing and thawing, allows both structure and viability to be retained almost indefinitely. Cryopreservation of various tissues has various controlled rates of freezing. MATERIAL AND METHOD: To find the optimal freezing curve and the chamber temperature, we approached the thermodynamic calculation of tissues in two ways. One is the direct calculation method. We should know the thermophysical characteristics of all components, latent heat of fusion, area, density and volume, etc. This kind of calculation is so sophisticated and some variables may not be determined. The other is the indirect calculation method. We performed the tissue freezing with already used freezing curve and we observed the actualfreezing curve of that tissue. And we modified the freezing curve with several steps of calculation, polynomial regression analysis, time constant calculation, thermal response calculation and inverse calculation of chamber temperature. RESULT: We applied that freezing program on mesenchymal stem cell, chondrocyte, and osteoblast. The tissue temperature decreased according to the ideal freezing curve without temperature rising. We did not find any differences in survival. The reason is postulated to be that freezing material is too small and contains cellular components. We expect the significant difference in cellular viability if the freezing curve is applied on a large scale of tissues. CONCLUSION: This program would be helpful in finding the chamber temperature for the ideal freezing curve easily.

Redo Operations for Recurrent Dissection After Operation for Type A Aortic Dissection / 대한흉부외과학회지

BACKGROUND: Stanford type A aortic dissection after graft replacement of ascending aorta and/or aortic arch required careful follow-up due to progression of the enlarged false lumen or the recurrence of dissection. From June 1984 to June 2000, 124 patients underwent operations for type A aortic dissection. Among them, 6 patients underwent reoperation due to recurred aneurysm or dissection. We evaluated that the causes of reoperation, including Marfan syndrome, the approach and result of reoperation, and strategy to reduce the risk of reoperation. MATERIAL AND METHOD: The first operation was done on acute stage in 4 cases, and chronic stage in 2 cases. There were Marfan syndromes in 3 cases. The entry site was the ascending aorta for all cases except one who underwent Bentall operation(n=3) or ascending aorta graft replacement(n=2). In one case, Bentall operation and total arch replacement was performed due to chronic type A dissection with multiple fenestrations. Mean interval of reoperation was 67.6months(range 5 months to 14 year 4months) after the first operation. Reoperations were performed with recurrence of dissection(n=4), threatening aneurysmal evolution of persisting dissection(n=1), and false aneurysm with infection(n=1). The redo operation involved the hemiarch in 1 case, distal ascending to total arch and descending thoracic aorta in 4 cases, and only descending thoracic aorta in 1 case. RESULT: There were Marfan syndromes in 18 patients. The mean age in type A dissection was 56.7 years and that in the first operation of reoperation cases was 32.2 years. Especially in 3 patients with Marfan syndrome, the mean age was 29 years. All patients who underwent reoperation survived. Postoperative complications were bleeding and tracheostomy in 1, mediastinitis in 1 and transient delirium in 1 case. Postoperatively, all the patients were followed-up in regular interval. Five patients were evaluated with computerized tomography, 1- 79months(mean: 31.5months) after the reoperation. The false lumen had regressed in 1 cases, persisted without progression in 4 cases. CONCLUSION: The clinical results of reoperation after type A aortic dissection operation were satisfactory. In younger patients with Marfan syndrome, the risk of reoperation was high. Careful and regular follow-up for the persistent false lumen is necessary.

Cellular Viability of Cryopreserved Porcine Valve According to Warm Ischemic Time / 대한흉부외과학회지

BACKGROUND: Valve replacement using cryopreserved valved homograft is increasing because of resistance of infection and excellent hemodynamics. The viability of fibroblast which is related with warm ischemic time affects the durability of implanted cryopreserved valved homograft. We evaluated how long the warm schemic time is acceptable by examining the viability of cells depending upon warm ischemic time. MATERIAL AND METHOD: 1. Retrieval of tissues; Thirty-two slaughted porcine heart and lung enblocs were stored at refrigerator(4~8 degreesC) for various time period(Warm Ischemic Time), and the heart was dissected and stored in Hartman solution at 4 degreesCfor 24 hours(Cold Ischemic Time) as the simulation of retrieval and dissection of human heart. The hearts were assigned to groups A(2 hours), B(12 hours), C(24 hours), D(36 hours) depending on warm ischemic time. 2. Sterilization; The valved homografts were sterilized in the RPMI 1640 solution with antibiotics. 3. Freezing and Storage; The homografts were freezed by computerized freezer, stored 7 days at liquid nitrogen tank, and thawed. 4. Evaluation of the viability; The viability was evaluated by Triphan blue test after warm ischemic time, after cold ischemic time and after thawing. 5. Analysis; The viability of fibroblast was analysed by pearson correlation test of SAS program. RESULT: 1. The viability between after cold ischemic time and after thawing was not different(p=0.619) for the adequacy of sterilization, freezing and thawing. 2. The viability which was evaluated after warm ischemic time, cold ischemic time and thawing, and the various warm ischemic times are strongly correlated as R is -0.857, -0.673 and -0.549 respectively. The viability of tricuspid valve is well related with the viability of aortic valve. CONCLUSION: 1. The longer the warm ischemic time, the lesser the viability of fibroblast. The viability of fibroblast after cryopreservation was decreased less 60% if the warm ischemic time was over 12 hours. 2. The method of cryopreservation is acceptable for maintaining the viability of fibroblast, and the viability of tricuspid valve may be the indicator of the viability of aortic valve. 3. However, the study for the optimal viability which is necessary to the durabiltiy of implanted valved homograft is needed.

Viability and enzymatic activity of cryopreserved porcine heart valve

Fibroblast viability of a natural tissue valve for replacing a defective heart valve through allograft or xenograft has been suggested to affect its clinical durability. In this study, the cell viability and enzymatic activity of porcine heart valve leaflets were examined in regard to concerning to the preservation process [variable warm ischemic time (WIT), cold ischemic time (CIT), and cryopreservation]. Porcine heart enblocs were obtained and valve dissection was performed after 2, 12, 24, or 36 hours, in respective groups A, B, C, and D, as WIT. Each group was stored for 24 hours as CIT and cryopreserved. Leaflets were dissected from a valved conduit after each process, and cell viability and enzymatic activity in the leaflet were investigated using trypan blue staining and API ZYM kits. WIT extension significantly decreased fibroblast viability (p < 0.05, 92.25 +/- 2.7% at 2 hours, 84.9 +/- 6.7% at 12 hours, 57.0 +/- 10.2% at 24 hours, 55.9 +/- 7.9% at 36 hours), while CIT for 24 hours was also influenced significantly (p < 0.05), whereas cryopreservation demonstrated no effect on cellular viability. In enzyme activity observation, several enzymes related to lipid or nucleotide degradation (esterase, esterase lipase, particularly phosphatase, phosphohydrolase) were remarkably changed following the valve-fabrication process. After 24 hours CIT, these enzymatic activities in groups B, C and D significantly increased, but the activities decreased after cryopreservation. Particularly, both the viability and enzymatic activity showed remarkable changes after CIT in group B (WIT = 12 hours). These results suggest that WIT is more important than CIT in maintaining viability of the valve, and that completing all the cryopreservation process within 12 hours after acquisition is recommended.

Animal Experiments of Heart Transplantation for Complicated Congenital Heart Disease in Neonate / 대한흉부외과학회지

BACKGROUND: Heart transplantation is considerated for a selected certain group of complicated congenital heart disease in neonates because corrective surgery is very difficult and has high mortality. Precise planning of transplantation is necessary to adequately fit the donor heart to the recipient. MATERIAL AND METHOD: We have performed 4 neonatal pig heart transplantations to test the technical feasibility. Experiment 1: The transplantation was performed using the same technique as the adult heart transplantation. Experiment 2: The transplantation for hypoplastic left heart syndrome was simulated as we reconstructed the whole aortic arch with donor aorta. Experiment 3: The heart transplantation was done with radical pulmonary artery reconstruction. Experiment 4: The experiment was performed for a long term survival. RESULT: Preoperative planning was very important for adequate fitting. All animals could be weaned from cardiopulmonary bypass, however, two animals died due to bleeding at pulmonary artery and left atrium. CONCLUSION: We concluded that the neonatal heart transplantation can be applied in some complicated Further using animal model is mandatory.

Endovascular Treatment of Abdominal Aortic Aneurysm by Bifurcated Stent Graft

PURPOSE: To evaluate the effectiveness and safety of endoluminal bifurcated stent graft for the treatment of AAA. MATERIALS AND METHODS: Between August 1997 and August 1998, 20 patients with AAA underwent treatment involving the use of a bifurcated stent graft. Fourteen in whom the aneurysm involved only bifurcation and six patients in whom the common iliac arteries were involved. For one patient, a stent with a short proximal neck measuring 12 mm was used. The stent graft was inserted by means of a unilateral surgical femoral arteriotomy. After the procedure, follow up involving CT and aortography was performed between month 3 and month 12. RESULTS: The primary success rate with the first trial was 79 percent (15 of 19 patients), and the overall success rate was 84 percent; one perigraft leak was successfully corrected. In one case, technical failure occurred due to a tortuous iliac vessel and spasm. Procedure-related complications occurred in 16% of patients (3 of 19), one of whom died due to acute renal failure following a contrast overdose. CONCLUSION: Endovascular treatment of infrarenal AAA by means of a bifurcated stent graft was effective and safe. In particular, if the proximal neck measured more than 1cm, any AAA could be treated using bifurcated stent graft. Further investigation of the outcome and complications arising during long-term follow-up are needed, however.

The Clinical Experiences of Patch Angioplasty in Isolated Critical Left Main Coronary Artery Stenosis / 대한흉부외과학회지

The conventional surgical treatment of isolated critical stenosis of the left main coronary artery restores a less physiologic perfusion of the myocardium, leads to occlusion of the left coronary ostium, and consumes an appreciable length of bypass material. From June 1994 to February 1996, eleven patients, three male and eight female, underwent patch angioplasty and additional bypass graft to left anterior descending artery (10 internal mammary artery, 1 saphenous vein) in isolated critical left main coronary artery stenosis. Their ages ranged from 34 to 62 years, mean 44 years. All had 60% to 90% stenosis of the left main coronary artery and Class III angina. The angiogram showed nine osteal lesion and three main stem stenosis. The operation was performed with conventional cardiopulmonary bypass and cold blood cardioplegia. We approached anteriorly and used bovine pericardium as onlay patch in all patients. There were one leg wound dehiscence, but no operative deaths and infarctions. All patients are free of symptoms after a mean follow-up of 15.5 months. Angiographic restudy at an average 14.4 months was obtained in five patients and showed widely patent left main coronary artery with excellent runoff. But additional graft to left anterior descending coronary artery were stenosed in two patients and showed diminutive flow in others. Our preliminary results suggest that angioplasty of the left main coronary artery can be carried out with low operative risks. But additional bypass graft to left anterior descending coronary artery may be unnecessary. The technique appears to be a promising alternative to conventional coronary artery bypass grafting in isolated left main coronary artery stenosis.

Aortic Root Replacement with Valve Preservation in a Patient with Annuloaortic Ectasia / 대한흉부외과학회지

Patients with aortic root disease, frequently seen in Marfan syndrome have progressive dilatation of the aortic sinuses and dilatation and distortion of the aortic annulus, leading to aortic incompetence. They are currently treated with composite graft replacement of the ascending aorta and aortic valve and reimplantation of the coronary arteries. Recently, we experienced an aortic root replacement with aortic valve preservation in a patient with annuloaortic ectasia. The ascending aorta and sinus was excised except the aortic annulus and aortic valve. The aortic valve was reimplanted inside of a collagen-impregnated tubular Dacron graft. The coronary arteries were also reimplanted. The patient was followed up for six months and reevaluated with the echocardiography. Postoperative Doppler echocardiography revealed normal aortic valve function. With this technique, it is possible to preserve the native aortic valve if the aortic leaflets are anatomically normal.

The Clinical Experiences of "New Duromedics Valve" Replacement / 대한흉부외과학회지

Between October 1991 and May 1995, 256 "New Duromedics Valve"(Edward TEKNA Bileaflet Valve) were implanted in 208 adult patients(171 mitral, 82 aortic and 3 tricuspid) with age ranging from 18 years to 70 years(mean 48.2+/-11.6 years). Postoperative complication rates were 12.2%, but there was none valve related one. Overall early mortality rate were 1.4%(1.6% for MVR, 2.1% for DVR, and none for AVR or TVR) respectively. Follow-up was 99% completed ranging in duration from 2 months to 46 months. There were 6 valve-related late complications(2.9%) with 2 patients with upper gastrointestinal bleeding, 2 with cerebral thromboembolism, 1 with valve thrombosis and 1 with valve endocarditis. Freedom from these valve-related major complications were 89.9% at 40 months. There were 5 late deaths(2.4%). one of these late deaths was considered valve-related. Overall actuarial survival rates at 40 months were 95.5%, 96.8% for mitral, 97.1% for aortic, 100% for tricuspid, and 92.0% for double valve replacement respectively. Preoperative New York Heart Association functional class were 2.9, and 1.3 in post-operative state. We have been trying to keep the international normalized ratio(INR) with range of 2.5 to 3.0. The INR of 4 patients of 5 with anticoagulant ralated complications was beyond the range. To reduce the rate of anticoagulant related complications, we felt very strongly that the INR should be kept between 2.5 and 3.0. In our cases, there was no structural failure or significant hemolysis in the absence of periprosthetic leak. This experience encourages us to continue using the "New Duromedics Valve".

Thromboendarterectomy for chronic pulmonary embolism under cardiopulmonary bypass: report of a case / 대한흉부외과학회지

No abstract available.