Inhibitory effect of the tricyclic antidepressant amitriptyline on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

Amitriptyline, a tricyclic antidepressant (TCA) drug, is widely used in treatment of psychiatric disorders. However, the side effects of amitriptyline on vascular K+ channels remain to be determined. Therefore, we investigated the effect of the tricyclic antidepressant and serotonin reuptake inhibitor amitriptyline on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells, using the whole-cell patch clamp technique. The Kv current amplitudes were inhibited by amitriptyline in a concentration-dependent manner, with an apparent IC50 value of 2.2 ± 0.14 µmol/L and a Hill coefficient of 0.87 ± 0.03. Amitriptyline shifted the activation curve to a more positive potential, but had no significant effect on the inactivation curve, suggesting that amitriptyline altered the voltage sensitivity of Kv channels. Pretreatment with Kv1.5 and Kv1.2 channel inhibitors did not alter the inhibitory effect of amitriptyline on Kv channels. Additionally, application of train pulses (1 and 2 Hz) did not affect amitriptyline-induced inhibition of Kv currents, which suggested that the action of amitriptyline on Kv channels was not use (state)-dependent. From these results, we concluded that amitriptyline inhibited the channels in a concentration-dependent, but state-independent manner.

A Case of Spontaneous Hemothorax with a Ruptured Variceal Phrenic Vein.

Spontaneous hemothorax is rare, with limited data available on its etiology and treatment. We report a case of massive spontaneous hemothorax with a ruptured variceal phrenic vein during pregnancy, likely a complication of the Kasai procedure. Despite closed thoracostomy, the patient's symptoms and imaging findings did not improve. Emergent open thoracotomy and bleeding control were performed.

Comparison of multivariate linear regression and a machine learning algorithm developed for prediction of precision warfarin dosing in a Korean population.

BACKGROUND: Personalized warfarin dosing is influenced by various factors including genetic and non-genetic factors. Multiple linear regression (LR) is known as a conventional method to develop predictive models. Recently, machine learning approaches have been extensively implemented for warfarin dosing due to the hypothesis of non-linear association between covariates and stable warfarin dose. OBJECTIVE: To extend the multiple linear regression algorithm for personalized warfarin dosing in a Korean population and compare with a machine learning--based algorithm. METHOD: From this cohort study, we collected information on 650 patients taking warfarin who achieved steady state including demographic information, indications, comorbidities, comedications, habits, and genetic factors. The dataset was randomly split into training set (90%) and test set (10%). The LR and machine learning (gradient boosting machine [GBM]) models were developed on the training set and were evaluated on the test set. RESULT: LR and GBM models were comparable in terms of accuracy of ideal dose (75.38% and 73.85%), correlation (0.77 and 0.73), mean absolute error (0.58 mg/day and 0.64 mg/day), and root mean square error (0.82 mg/day and 0.9 mg/day), respectively. VKORC1 genotype, CYP2C9 genotype, age, and weight were the highest contributors and could obtain 80% of maximum performance in both models. CONCLUSION: This study shows that our LR and GMB models are satisfactory to predict warfarin dose in our dataset. Both models showed similar performance and feature contribution characteristics. LR may be the appropriate model due to its simplicity and interpretability.

Long-Term Left Atrial Function after Device Closure and Surgical Closure in Adult Patients with Atrial Septal Defect.

BACKGROUND: Studies comparing left atrial (LA) function after surgical closure or percutaneous closure in patients with an atrial septal defect (ASD) are lacking. METHODS: Between 1 and 3 years after ASD treatment, we retrospectively analyzed the medical records and transthoracic echocardiographic images of patients who had been diagnosed with an ASD after 20 years of age and who had undergone surgical closure (ASD-S) or percutaneous device closure (ASD-D). We measured LA peak systolic, early diastolic, and late diastolic strain values using 2-dimensional (2D) speckle tracking echocardiography (STE) and calculated reservoir, conduit, and contraction strain. RESULTS: The reservoir strain value of the ASD-D groups was 25.2% ± 7.4%, which was lower compared to the control group (33.6% ± 5.5%) (p = 0.004). The LA conduit strain and the LA contraction values of the ASD-D group were also lower compared to the control group (-13.8% ± 5.8% vs. -20.4% ± 4.7%, p = 0.034; -11.3% ± 4.2% vs. -13.2% ± 2.5%, p = 0.037, respectively). The reservoir, conduit, and contraction strains of the ASD-S group were 27.8% ± 8.8%, -15.3% ± 6.4%, and -12.5% ± 5.8%, respectively, and were not different from those of the control group or the ASD-D group. CONCLUSIONS: The 2D STE is a suitable method for evaluating LA function after ASD closure. Our results demonstrate that 1 year after device closure, the LA reservoir, conduit and contraction function were reduced in ASD-D group compared to healthy controls, while there was no difference between the ASD-S and ASD-D groups.

Does strong hypertrophic condition induce fast mitochondrial DNA mutation of rabbit heart?

Homo- and heteroplasmic mitochondrial DNA (mtDNA) mutations were observed and identified in an isoproterenol-induced rabbit model of cardiac hypertrophy. Genes encoding proteins essential for catalyzing mitochondrial electron transfer and for generating the proton motive force, such as NADH dehydrogenases (ND2, ND3, ND4, and ND6), cytochrome b, and ATPase 8, showed increased susceptibility for mutation. Specifically, five mutations caused amino acid changes and were located in Complex I and Complex V gene clusters. To our knowledge, this is the first demonstration of a relationship between cardiac hypertrophy induced by a strong sympathetic load and rapid mtDNA mutations.

The vasorelaxant effect of mitiglinide via activation of voltage-dependent K+ channels and SERCA pump in aortic smooth muscle.

AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca2+-activated K+ (BKCa) channel blocker paxilline, inwardly rectifying K+ (Kir) channel blocker Ba2+, and ATP-sensitive K+ (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide. However, application of the voltage-dependent K+ (Kv) channel blocker 4-AP, effectively inhibited mitiglinide-induced vasorelaxation. Although pretreatment with the Ca2+ channel blocker nifedipine did not alter the mitiglinide-induced vasorelaxation, pretreatment with the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitor thapsigargin and cyclopiazonic acid reduced the vasorelaxant effect of mitiglinide. In addition, the vasorelaxant effect of mitiglinide was not affected by the inhibitors of adenylyl cyclase, protein kinase A, guanylyl cyclase, or protein kinase G. Elimination of the endothelium and inhibition of endothelium-dependent vasorelaxant mechanisms also did not change the vasorelaxant effect of mitiglinide. SIGNIFICANCE: We proposed that mitiglinide induces vasorelaxation via activation of Kv channels and SERCA pump. However, the vasorelaxant effects of mitiglinide did not involve other K+ channels, Ca2+ channels, PKA/PKG signaling pathways, or the endothelium.

Fucoxanthin inhibits profibrotic protein expression in vitro and attenuates bleomycin-induced lung fibrosis in vivo.

Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-ß1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-ß1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated. We performed an enzyme-linked immunosorbent assay (ELISA), and a western blot analysis to elucidate the mechanisms underlying the antifibrotic effects of Fx in TGF-ß1-stimulated cells. The contractile activity of HPFs was measured using a collagen gel contraction assay. We also investigated the effects of Fx on inflammation and fibrosis in bleomycin (BLM)-induced pulmonary fibrosis mouse model. We observed that Fx inhibited the TGF-ß1-induced expression of α-SMA, type 1 collagen, fibronectin, and IL-6 in HPFs. Similarly, markedly inhibition of TGF-ß1-induced phosphorylation of p-38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and Smad2/Smad3 (Smad2/3) was observed after Fx treatment. Collagen contraction also significantly decreased on fucoxanthin treatment. Intraperitoneal injection of Fx (10mg/kg) in mice inhibited BLM-induced lung fibrosis and type I collagen protein expression. Overall, our findings suggest that Fx may be effective in the treatment of pulmonary fibrosis owing to its potent antifibrotic activity.

Pseudoaneurysm with Arteriovenous Fistula after Arthroscopic Procedure: A Rare Complication of Arthroscopy.

Pseudoaneurysm with arteriovenous fistula is a rare complication of arthroscopy, and can be diagnosed by ultrasonography, computed tomography, magnetic resonance imaging, or angiography. This condition can be treated with open surgical repair or endovascular repair. We report our experience with the open surgical repair of a pseudoaneurysm with an arteriovenous fistula in a young male patient who underwent arthroscopy five months previously.

Intraoperative balloon angioplasty using fogarty artertial embolectomy balloon catheter for creation of arteriovenous fistula for hemodialysis: single center experience.

BACKGROUND: The purpose of this study was to evaluate the use of a Fogarty arterial embolectomy catheter (Fogarty catheter) in intraoperative balloon angioplasty of the cephalic vein, in order to determine its effect on the patency of arteriovenous fistulas (AVFs) created for hemodialysis access. METHODS: A total of 156 patients who underwent creation of an AVF were divided into two groups, based whether a Fogarty catheter was used during AVF creation. Group A (89 patients) comprised the patients who underwent balloon angioplasty with a Fogarty catheter during the operation. Group B (67 patients) included the patients in whom a Fogarty catheter was not used during the operation. Patient records were reviewed retrospectively and documented. The patency rate was determined by the Kaplan-Meier method. RESULTS: The records of 156 patients who underwent the creation of an AVF from January 2007 to October 2011 were included. The mean follow-up duration was 40.2±19.4 months (range, 1 to 97 months). The patency rates in group A at 12, 36, and 72 months were 83.9%±3.9%, 78.3%±4.6%, and 76.3%±4.9%, respectively, while the corresponding patency rates in group B were 92.5%±3.2%, 82.8%±0.5%, and 79.9%±5.7%, respectively. The patency rates in group B were found to be slightly higher than those in group A, but the difference was not statistically significant (p=0.356). CONCLUSION: Intraoperative balloon angioplasty of the cephalic vein using the Fogarty catheter is a simple and easily reproducible procedure, and it can be helpful in increasing AVF patency in cases of insufficient runoff or a suboptimal cephalic vein.

The NADPH oxidase inhibitor DPI can abolish hypoxia-induced apoptosis of human kidney proximal tubular epithelial cells through Bcl2 up-regulation via ERK activation without ROS reduction.

AIMS: Ischemia/reperfusion injury (IRI), resulting from hypoxic damage within a graft, is the leading cause of cell death and graft rejection. In this study, we investigated whether a HIF-1α inhibitor or various antioxidants were able to prevent ischemic injury in a cellular model in which experimental hypoxia was induced using CoCl2. MAIN METHODS: The ischemic injury induced in HK-2 cells by CoCl2 was validated by increased reactive oxygen species (ROS) production, reduced cell viability, and increased apoptosis at different times and doses. The preventative effects of various anti-oxidants on ischemic injury were evaluated using ROS levels, cell viability, and apoptosis. The MAPK phosphorylation status and Bcl2/Bax expression levels were evaluated after treatment with various antioxidants. KEY FINDINGS: The increase in ROS induced by hypoxia was significantly inhibited by NAC and CAPE, but not by any other treatment. The reduction in cell viability induced by CoCl2 was significantly inhibited by NAC and DPI, but not by any other treatment. The apoptosis induced by CoCl2 was also significantly inhibited by NAC and DPI, but not by any other treatment. Moreover, NAC and DPI prevented CoCl2-induced apoptosis in HK-2 cells in a dose- and time-dependent manner. Treatment of CoCl2 and HK-2 cells treated with DPI, but not NAC, significantly induced ERK activation and Bcl2 expression. NAC and DPI treatment prevented the apoptosis of cells cultured under hypoxic conditions. SIGNIFICANCE: Our results suggest that DPI should be investigated further as a novel protective agent that prevents kidney ischemia.

Cardiac hemangioma: a case report.

Hemangioma of the heart, presenting as a primary cardiac tumor is extremely rare; it accounts for approximately 2% of all primary resected heart tumors. In our patient, the tumor was located in the orifice of the right lower pulmonary vein. Few cases of cardiac hemangiomas have been reported to arise from the left atrial (LA) wall. Left atrial hemangiomas, especially those attached to the LA wall, may be erroneously diagnosed as myxomas. Cardiac hemangioma is a rare disease; furthermore, a tumor arising from the LA wall and misconceived as a myxoma is extremely rare. We removed a mass misdiagnosed as a myxoma; it was pathologically confirmed to be a cardiac capillary hemangioma. Therefore, we report a rare case of a cardiac hemangioma misconceived as a myxoma; the tumor was removed successfully.

Clinical Analysis of Radiocephalic Fistula Using Side-to-side Anastomosis with Distal Cephalic Vein Ligation.

BACKGROUND: The surgically created arteriovenous fistula has recently been recommended as the best available angioaccess for hemodialysis. Therefore, in this study, we carried out a clinical analysis on surgical procedures in the ligation and division of a distal vein to achieve similar effects as those of vein end-to-arterial side after side-to-side anastomosis. METHODS: We retrospectively reviewed the clinical data of 113 patients who came for an outpatient clinic follow-up to the department of internal medicine of our hospital; these patients were among the 125 patients who underwent radiocephalic arteriovenous fistula (side-to-side anastomosis with distal vein ligation and division) in our hospital in the period from January 2006 to December 2010. RESULTS: The patency rate showed no statistical significance with respect to sex (p=0.775), age (p=0.775), hypertension (p=0.262), diabetes (p=0.929), and cardio-neurovascular disease (p=0.717). Patency rates were 96% for the first month, 93% for the first year, and 90% for the second year for the radiocephalic arteriovenous fistula (side-to-side anastomosis with distal vein ligation and division) performed on the wrist. CONCLUSION: The patency rates revealed favorable results and few postoperative complications as compared to those of previous reports. Therefore, radiocephalic fistula using side-to-side anastomosis with distal cephalic vein ligation is considered a recommendable surgical procedure in the distal part for the hemodialysis of CRF patients.

Left and right ventricular strain and strain rate measurement in normal adults using velocity vector imaging: an assessment of reference values and intersystem agreement.

Velocity vector imaging (VVI) software permits quantitative assessment of ventricular function through measurement of myocardial strain (S) and strain rate (SR). The purpose of this study was to define a reference range of ventricular S and SR values in normal adults using VVI software, and to describe the variability among observers and systems. Two-dimensional echocardiography was performed in 186 healthy adults free of cardiovascular disease or risk factors, followed by comprehensive ventricular S and SR analysis using VVI software. Images were acquired using three commercial ultrasound systems. The mean age of patients was 44 ± 16 years, and 114 (61 %) were female. Mean global left ventricular (LV) longitudinal, circumferential, and radial S and SR, and right ventricular (RV) longitudinal S and SR values are presented. Significant segmental variation in regional LV and RV S and SR was detected. Multivariate regression analysis demonstrated global longitudinal LV (p = 0.05) and RV (p = 0.002) S values decline significantly with age. The overall variability of S and SR values accounted for by patient demographic and hemodynamic variables was low (16 and 8 % for LV longitudinal S and SR, respectively). Interobserver agreement was very good, but was lowest for LV radial S and SR. There were no significant differences of LV and RV S and SR between ultrasound systems. Comprehensive reference values for the normal ranges of LV and RV S and SR measured using VVI software are presented. The ultrasound system used for image acquisition did not significantly influence results.

Primary synovial sarcoma of the parietal pleura: a case report.

Synovial sarcoma is a malignant soft tissue tumor that most commonly occurs in the extremities of young and middle-aged adults, in the vicinity of large joints. Although synovial sarcoma is frequently associated with joints, it may arise in unexpected sites, such as the mediastinum, heart, lung, pleura, or chest wall. Primary synovial sarcoma of the pleura is rare. To date, nearly 36 cases of primary synovial sarcoma of the pleura have been reported since Gaertner et al. published the first case in 1996. The oncologic characteristics, treatment, and prognosis for pleural synovial sarcomas are not well defined because of a paucity of data. However, a multimodal approach, including surgical resection, chemotherapy, and radiotherapy, has generally been suggested. We report the outcome of one patient with primary pleural synovial sarcoma treated with radical resection and adjuvant treatment.

Primary surgical closure should be considered in premature neonates with large patent ductus arteriosus.

BACKGROUND: Treatment for patent ductus arteriosus (PDA) in premature infants can consist of medical or surgical approaches. The appropriate therapeutic regimen remains contentious. This study evaluated the role of surgery in improving the survival of premature neonates weighing less than 1,500 g with PDA. MATERIALS AND METHODS: From January 2008 to June 2011, 68 patients weighing less than 1,500 g with PDA were enrolled. The patients were divided into three groups: a group managed only by medical treatment (group I), a group requiring surgery after medical treatment (group II), and a group requiring primary surgical treatment (group III). RESULTS: The rate of conversion to surgical methods due to failed medical treatment was 67.6% (25/37) in the patients with large PDA (≥2 mm in diameter). The number of patients who could be managed with medical treatment was nine which was only 20.5% (9/44) of the patients with large PDA. There was no surgery-related mortality. Group III displayed a statistically significantly low rate of development of bronchopulmonary dysplasia (BPD) (p=0.008). The mechanical ventilation time was significantly longer in group II (p=0.002). CONCLUSION: Medical treatment has a high failure rate in infants weighing less than 1,500 g with PDA exceeding 2.0 mm. Surgical closure following medical treatment requires a longer mechanical ventilation time and increases the incidence of BPD. Primary surgical closure of PDA exceeding 2.0 mm in the infants weighing less than 1,500 g should be considered to reduce mortality and long-term morbidity events including BPD.

Recurrent true brachial artery aneurysm.

True aneurysm of the brachial artery is a rare disease entity. The mechanism of aneurysm formation is considered to be compression of the arterial wall, producing contusion of the media and subsequent weakness of the wall and fusiform dilatation. It can be caused by arteriosclerotic, congenital, and metabolic disorders, and can be associated with diseases such as Kawasaki's disease. Doppler ultrasonography, computed tomography, arteriography, and selective upper extremity angiography may be performed for establishing the diagnosis of aneurysm. The best therapeutic option is operative repair, and it should be performed without any delay, in order to prevent upper extremity ischemic or thrombotic sequelae. Here, we report a case of recurrent brachial artery aneurysm with review of the literature.

Chylopericardium Secondary to Lymphangiomyoma - A case report -.

Chylopericardium is a rare disease entity characterized by the accumulation of chylous fluid in the pericardial sac. It usually arises from mediastinal neoplasms, thrombosis of the subclavian vein, tuberculosis, nonsurgical trauma, thoracic or cardiac surgery. The spectrum of symptoms for chylopericardium varies from an incidental finding of cardiomegaly to dyspnea, upper abdominal discomfort, cough, chest pain, palpitation, fatigue. However, most of the patients are asymptomatic. The main purpose of treatment of chylopericardium is the prevention of cardiac tamponade and prevention of metabolic, nutritional, and immunological compromise due to chyle leak. Here, we report a case of chylopercardium secondary to lymphangiomyoma with review of the literature.