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PURPOSE: Pulmonary Kv channels are thought to play a crucial role in the regulation of cell proliferation and apoptosis. Previous studies have shown that fluoxetine upregulated the expression of Kv1.5 and prevented pulmonary arterial hypertension in monocrotaline-induced or hypoxia-induced rats and mice. The current study was designed to test how fluoxetine regulates Kv1.5 channels, subsequently promoting apoptosis in human PASMCs cultured in vitro. MATERIALS AND METHODS: Human PASMCs were incubated with low-serum DMEM, ET-1, and fluoxetine with and without ET-1 separately for 72 h. Then the proliferation, apoptosis, and expression of TRPC1 and Kv1.5 were detected. RESULTS: In the ET-1 induced group, the upregulation of TRPC1 and down regulation of Kv1.5 enhanced proliferation and anti-apoptosis, which was reversed when treated with fluoxetine. The decreased expression of TRPC1 increased the expression of Kv1.5, subsequently inhibiting proliferation while promoting apoptosis. CONCLUSION: The results from the present study suggested that fluoxetine protects against big endothelin-1 induced anti-apoptosis and rescues Kv1.5 channels in human pulmonary arterial smooth muscle cells, potentially by decreasing intracellular concentrations of Ca2+.
Subject(s)
Humans , Apoptosis/drug effects , Blotting, Western , Cell Proliferation/drug effects , Cells, Cultured , Endothelin-1/pharmacology , Flow Cytometry , Fluoxetine/pharmacology , /genetics , Muscle, Smooth, Vascular/cytology , Pulmonary Artery/cytology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Objective It is controversial to the surgical treatment of the DeBakey I aortic dissection.The purpose of the study was to summarize the clinical experience on total arch replacement combined with implantation of stented elephant trunk into the descending aorta for DeBakey I aortic dissection.Methods From June 2005 to March 2008,41 consecutive patients with acute(in 31)or chronic(in 10)DeBakey I aortic dissection underwent total arch replacement combined with implantation of stented elephant trunk into the descending aorta.The mean age was 57(27～76)years.Thirty-two patients were male.The procedure was performed under deep hypothermic circulatory arrest and selected cerebral perfusion.The stented elephant trunk was implanted through the aortic arch under deep hypothermic circulatory arrest.The stented elephant trunk was an 8～10 cm long self-expandable graft.Concomitant procedures included Bentall operation and total arch replacement in 24,Wheat operation and total arch replacement in 6,ascending aorta and total arch replacement in 11.Computed tomography was performed in every patient before discharge to evaluate the postoperative outcomes of the procedure.Results Cardiopulmonary bypass time was(168±32)min.The cross clamp time was(109±24)min and selective cerebral perfusion and the lowerbody circulatory arrest time wsa(31±11)min.The in-hospital mortality was 4.9%(2/41).One patient died of hemorrhagic shock and another died of multi-organ failure postoperatively.Fourteen cases suffered complications and 12 cases were cured.One case died of the cerebral hemorrhage after 4 months due to inappropriate anticoagulation during follow up.Conclusion Ascending aorta and total aortic arch replacement combined with implantation of stented trunk into descending aorta is a safe,effective and feasible way in closing the residual false lumen of the descending aorta with a low morbidity and mortality.This procedure might contribute to a better long-term outcomes of DeBakey I aortic dissection.
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Objective To summarise the clinical experience on the treatment of aortic dissection with stent-graft. Methods From June 2005 to November 2008, 117 patients with aortic dissection underwent surgery with stented elephant trunk (CRONUS stent-graft)which was implanted through the aortic arch under deep hypothermic circulatory arrest, including Stanford A in 50 patients who underwent Bentall operation and total arch grafting with stented elephant trunk operation in 28, Wheat operation and total arch grafting with stented elephant trunk operation in 8, ascending aorta and total arch replacement with stented elephant trunk operation in 14 and Stanford B in 67 patients who all underwent stented elephant trunk operation. Results The location of the entry was in the ascending aorta in 35 patients, the aortic arch in 4, the proximal descending aorta in 78. Cardiopulmonary bypass time was ( 159 ±31 ) min, average cross clamp time was (95 ±23) min, and average selected cerebral perfusion and lowerbody arrest time was (27 ±8) min. The in-hospital mortality was 2.6% (3/117). One patient died of the hemorrhage shock, one died of multi-organ failure postoperatively and the third died of infective endocarditis. The complications included transient neurologic deficit in 11(9.4%), cerebrovascular accident in 6 (5. 1%, cerebral embolism in 2 and cerebral hemorrhage in 4, of which 5 cases were discharged from hospital. One case died of multiorgan failure 18 days after discharge owing to his family' s giving up treatment), hemorrhage of anastomose which was treated by reoperation in 5,hoarseness in 2, renal failure in 1. One case died of the cerebral hemorrhage after 4 months due to inappropriate anticoagulation during following up. Conclusion The treatment of the aortic dissection with stent-graft which was implanted into the descending aorta through aorta arch is safe, effective and feasible, which will be helpful to vascular reconstruction by accurately close subintimal rip and can streamline surgery with minimally invasive and less complications.
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Objective To investigate the effect of calcium channel antagonist verapamil upon coronary vessel disease of allograft heart transplant rat model.Methods 160 SD rats weighing 220 to 300 g were randomly allocated to control group (group 1, n=40) and experiment groups (group 2, n=40; group 3, n=40, group 4, n=40). The hearts of all donor rats were implanted into the recipient rats. From the day after operation, the rats in each group were fed routinely and injected intraperitoneally (ip) with Cyclosporin (5 mg?kg~ -1?d~ -1 for 10 days). In experiment groups, the rats were individually injected (ip) with verapamil by 0.1 mg/kg,0.5 mg/kg,1.0 mg/kg twice every day for 3 months, but the rats in control group were not subjected to injection. At 60th and 90th day after grafting, 10 of each group were selected randomly and transplanted hearts were cut. The specimens were stained with HE and histochemistry.Result The degree of intimal hyperplasia in the control group was more severe than in the experiment groups.Conclusion Calcium channel antagonist verapamil can effectively inhibit the intimal hyperplasia of coronary arteries in heart transplant model.
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Objective To compare the myocardial protective effect between off pump coronary artery bypass(OPCAB) and on pump coronary artery bypass in the aged. Methods Four five patients were randomly divided into 3 groups:off pump coronary artery bypass (n=15),tepid blood cardioplegia group(n=15) and cold blood cardioplegia group (n=15).There was no statistical difference in heart function,sex,age and lesion of coronary artery .Venous blood samples were taken for determineing the serum concentration of creatine kinase MB isoenzyme(CK MB),troponin I perioperatively and the clinical situations were observed postoperatively. Results CK MB,troponin I release in beating group during and after bypass was lower than that in on pump groups( P
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Objective To review the experience of closure of recalcitrant bronchopleural fistula using the transsternal transpericardial approach. Methods 3 patients with recalcitrant bronchopleural fistula underwent transsternal transpericardial closure of a bronchopleural fistula and drainage by open thoracostomy. Results All patients were survived and there was no recurrence of bronchopleural fistula. Conclusion Transsternal transpericardial approach seems to be a safe and effective method in cases of bronchopleural fistula complicated with empyema. It has the added advantage of less recurrent fistula formation.
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Objective: To investigate the etiological factors and treatment for a rare evacuation disturbance and severe dilatation syndrome of transplanted colon for esophagus diseases. Methods: From 1962 to 1999, 548 patients with colon replacement for esophagus were studied. 425 patients were followed-up for 0 5 to 10 years. 9 patients with thoracic colon syndrome were operated on from 1970 to 1980. The clinical sign, experiment test, etiological factor and method of treatment were reviewed. Results: 5 patients had large anastomotic stoma of colon-stomach, 2 had angulation of abdominal part colon, and 2 had mechanical obstruction. 7 patients were cured after reoperation. Clinical symptoms of other 2 patients were remission after drug treatment. No thoracic colon syndrome occurred after 1980. Conclusion: The etiological factors of thoracic colon syndrome were too large colon-stomach anastomotic stoma, angulation of long-winded colon in abdomen part colon and mechanical obstruction. Colon-stomach stoma should be 1/2 to 2/3 of intestinal luminal diameter and anti-reflux operation should be done at the same time. The pyloroplasty is essential when truncal vagotomy has been done during the operation.