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1.
Chem Rev ; 124(10): 6393-6443, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38669641

ABSTRACT

Traditionally, alkaline water electrolysis (AWE) uses diaphragms to separate anode and cathode and is operated with 5-7 M KOH feed solutions. The ban of asbestos diaphragms led to the development of polymeric diaphragms, which are now the state of the art material. A promising alternative is the ion solvating membrane. Recent developments show that high conductivities can also be obtained in 1 M KOH. A third technology is based on anion exchange membranes (AEM); because these systems use 0-1 M KOH feed solutions to balance the trade-off between conductivity and the AEM's lifetime in alkaline environment, it makes sense to treat them separately as AEM WE. However, the lifetime of AEM increased strongly over the last 10 years, and some electrode-related issues like oxidation of the ionomer binder at the anode can be mitigated by using KOH feed solutions. Therefore, AWE and AEM WE may get more similar in the future, and this review focuses on the developments in polymeric diaphragms, ion solvating membranes, and AEM.

2.
J Chest Surg ; 57(2): 184-194, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38360679

ABSTRACT

Background: Left ventricular assist devices (LVADs) are widely employed as a therapeutic option for end-stage heart failure. We evaluated the outcomes associated with centrifugal-flow LVAD implantation, comparing 2 device models: the Heartmate 3 (HM3) and the Heartware Ventricular Assist Device (HVAD). Methods: Data were collected from patients who underwent LVAD implantation between June 1, 2015 and December 31, 2022. We analyzed overall survival, first rehospitalization, and early, late, and LVAD-related complications. Results: In total, 74 patients underwent LVAD implantation, with 42 receiving the HM3 and 32 the HVAD. A mild Interagency Registry for Mechanically Assisted Circulatory Support score was more common among HM3 than HVAD recipients (p=0.006), and patients receiving the HM3 exhibited lower rates of preoperative ventilator use (p=0.010) and extracorporeal membrane oxygenation (p=0.039). The overall early mortality rate was 5.4% (4 of 74 patients), with no significant difference between groups. Regarding early right ventricular (RV) failure, HM3 implantation was associated with a lower rate (13 of 42 [31.0%]) than HVAD implantation (18 of 32 [56.2%], p=0.051). The median rehospitalization-free period was longer for HM3 recipients (16.9 months) than HVAD recipients (5.3 months, p=0.013). Furthermore, HM3 recipients displayed a lower incidence of late hemorrhagic stroke (p=0.016). In the multivariable analysis, preoperative use of continuous renal replacement therapy (odds ratio, 22.31; p=0.002) was the only significant predictor of postoperative RV failure. Conclusion: The LVAD models (HM3 and HVAD) demonstrated comparable overall survival rates. However, the HM3 was associated with a lower risk of late hemorrhagic stroke.

3.
J Chest Surg ; 57(3): 272-280, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38374156

ABSTRACT

Background: The phenomenon known as the "weekend effect" impacts various medical disciplines. We compared outcomes between regular hours and off hours to investigate the presence of the weekend effect in extracorporeal cardiopulmonary resuscitation (ECPR). Methods: Between January 2018 and December 2020, 159 patients at our center were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) for cardiac arrest. We assessed the time required for ECMO preparation, the rate of successful weaning, and the rate of in-hospital mortality. These factors were compared among regular hours ("daytime": weekdays from 7:00 AM-7:00 PM), off hours on weekdays ("nighttime": weekdays from 7:00 PM-7:00 AM), and off hours on weekends and holidays ("weekend": Fridays at 7:00 PM to Mondays at 7:00 AM). Results: The time from the recognition of cardiac arrest to the arrival of the ECMO team was shortest for the daytime group and longest for those treated over the weekend (daytime, 10.0 minutes; nighttime, 12.5 minutes; weekend, 15.0 minutes; p=0.064). The time from the ECMO team's arrival to ECMO initiation was shortest for the daytime and longest for the nighttime group (daytime, 13.0 minutes; nighttime, 18.5 minutes; weekend, 14.0 minutes; p=0.028). No significant difference was observed in the rate of successful ECMO weaning (daytime, 48.3%; nighttime, 39.5%; weekend, 36.1%; p=0.375). Conclusion: In situations involving CPR, the time to arrival of the ECMO team was longer during off hours. Furthermore, ECMO insertion required more time at night than during the other periods. These findings warrant specific training in decision-making and emergent ECMO insertion.

4.
J Chest Surg ; 56(6): 394-402, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37696780

ABSTRACT

Background: The optimal choice of valve substitute for aortic valve replacement (AVR) in pediatric patients remains a matter of debate. This study investigated the outcomes following AVR using mechanical prostheses in children. Methods: Forty-four patients younger than 15 years who underwent mechanical AVR from March 1990 through March 2023 were included. The outcomes of interest were death or transplantation, hemorrhagic or thromboembolic events, and reoperation after mechanical AVR. Adverse events included any death, transplant, aortic valve reoperation, and major thromboembolic or hemorrhagic event. Results: The median age and weight at AVR were 139 months and 32 kg, respectively. The median follow-up duration was 56 months. The most commonly used valve size was 21 mm (14 [31.8%]). There were 2 in-hospital deaths, 1 in-hospital transplant, and 1 late death. The overall survival rates at 1 and 10 years post-AVR were 92.9% and 90.0%, respectively. Aortic valve reoperation was required in 4 patients at a median of 70 months post-AVR. No major hemorrhagic or thromboembolic events occurred. The 5- and 10-year adverse event-free survival rates were 81.8% and 72.2%, respectively. In univariable analysis, younger age, longer cardiopulmonary bypass time, and smaller valve size were associated with adverse events. The cut-off values for age and prosthetic valve size to minimize the risk of adverse events were 71 months and 20 mm, respectively. Conclusion: Mechanical AVR could be performed safely in children. Younger age, longer cardiopulmonary bypass time and smaller valve size were associated with adverse events. Thromboembolic or hemorrhagic complications might rarely occur.

5.
J Chest Surg ; 56(1): 25-32, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36517949

ABSTRACT

Background: We reviewed the clinical outcomes of patients with oligometastatic (OM) non-small cell lung cancer (NSCLC) who received multimodal therapy including lung surgery. Methods: We retrospectively analyzed 117 patients with OM NSCLC who underwent complete resection of the primary tumor from 2014 to 2017. Results: The median follow-up duration was 2.91 years (95% confidence interval, 1.48-5.84 years). The patients included 73 men (62.4%), and 76 patients (64.9%) were under the age of 65 years. Based on histology, 97 adenocarcinomas and 14 squamous cell carcinomas were included. Biomarker analysis revealed that 53 patients tested positive for epidermal growth factor receptor, anaplastic lymphoma kinase, or ROS1 mutations, while 36 patients tested negative. Metastases were detected in the brain in 74 patients, the adrenal glands in 12 patients, bone in 5 patients, vertebrae in 4 patients, and other locations in 12 patients. Radiation therapy for organ metastasis was performed in 81 patients and surgical resection in 27 patients. The 1-year overall survival (OS) rate in these patients was 82.8%, and the 3- and 5-year OS rates were 52.6% and 37.2%, respectively. Patients with positive biomarker test results had 1-, 3-, and 5-year OS rates of 98%, 64%, and 42.7%, respectively. These patients had better OS than those with negative biomarker test results (p=0.031). Patients aged ≤65 years and those with pT1-2 cancers also showed better survival (both p=0.008). Conclusion: Surgical resection of primary lung cancer is a viable treatment option for selected patients with OM NSCLC in the context of multimodal therapy.

6.
Polymers (Basel) ; 14(6)2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35335503

ABSTRACT

Hydrogen is nowadays considered a favorable and attractive energy carrier fuel to replace other fuels that cause global warming problems. Water electrolysis has attracted the attention of researchers to produce green hydrogen mainly for the accumulation of renewable energy. Hydrogen can be safely used as a bridge to successfully connect the energy demand and supply divisions. An alkaline water electrolysis system owing to its low cost can efficiently use renewable energy sources on large scale. Normally organic/inorganic composite porous separator membranes have been employed as a membrane for alkaline water electrolyzers. However, the separator membranes exhibit high ionic resistance and low gas resistance values, resulting in lower efficiency and raised safety issues as well. Here, in this study, we report that zirconia toughened alumina (ZTA)-based separator membrane exhibits less ohmic resistance 0.15 Ω·cm2 and low hydrogen gas permeability 10.7 × 10-12 mol cm-1 s-1 bar-1 in 30 wt.% KOH solution, which outperforms the commercial, state-of-the-art Zirfon® PERL separator. The cell containing ZTA and advanced catalysts exhibit an excellent performance of 2.1 V at 2000 mA/cm2 at 30 wt.% KOH and 80 °C, which is comparable with PEM electrolysis. These improved results show that AWEs equipped with ZTA separators could be superior in performance to PEM electrolysis.

7.
Front Chem ; 9: 787787, 2021.
Article in English | MEDLINE | ID: mdl-34869233

ABSTRACT

Alkaline water electrolysis (AWE) is a mature water electrolysis technology that can produce green hydrogen most economically. This is mainly attributed to the use of Ni-based materials that are easy to process and inexpensive. The nickel-based meshes with various structures such as woven mesh and expanded mesh are widely used as electrode in the AWE due to its common availability and easy fabrication. However, the morphological effect of meshes on hydrogen evolution reaction (HER) performance has not been studied. Here a new parameter to determine the structural effect of mesh on HER performance was first proposed. The key factors of the parameter were found to be the strand width, pore width and the strand surface area. The woven mesh with the ratio of pore width to strand width that converges to 1 showed the lowest the overpotential. The expanded mesh with the higher the structural surface area exhibited the lowest the overpotential. This study will help to choose an optimal structure for the mesh with the HER electrode.

8.
J Chest Surg ; 54(5): 348-355, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-34611083

ABSTRACT

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare disease often requiring mechanical ventilation after birth. In severe cases, extracorporeal membrane oxygenation (ECMO) may be needed. This study analyzed the outcomes of patients with CDH treated with ECMO and investigated factors related to in-hospital mortality. METHODS: Among 254 newborns diagnosed with CDH between 2008 and 2020, 51 patients needed ECMO support. At Asan Medical Center, a multidisciplinary team approach has been applied for managing newborns with CDH since 2018. Outcomes were compared between hospital survivors and nonsurvivors. RESULTS: ECMO was established at a median of 17 hours after birth. The mean birth weight was 3.1±0.5 kg. Twenty-three patients (23/51, 45.1%) were weaned from ECMO, and 16 patients (16/51, 31.4%) survived to discharge. The ECMO mode was veno-venous in 24 patients (47.1%) and veno-arterial in 27 patients (52.9%). Most cannulations (50/51, 98%) were accomplished through a transverse cervical incision. No significant between-group differences in baseline characteristics and prenatal indices were observed. The oxygenation index (1 hour before: 90.0 vs. 51.0, p=0.005) and blood lactate level (peak: 7.9 vs. 5.2 mmol/L, p=0.023) before ECMO were higher in nonsurvivors. Major bleeding during ECMO more frequently occurred in nonsurvivors (57.1% vs. 12.5%, p=0.007). In the multivariate analysis, the oxygenation index measured at 1 hour before ECMO initiation was identified as a significant risk factor for in-hospital mortality (odds ratio, 1.02; 95% confidence interval, 1.01-1.04; p=0.05). CONCLUSION: The survival of neonates after ECMO for CDH is suboptimal. Timely application of ECMO is crucial for better survival outcomes.

9.
Korean J Thorac Cardiovasc Surg ; 54(3): 221-223, 2021 06 05.
Article in English | MEDLINE | ID: mdl-33173019

ABSTRACT

Giant coronary artery aneurysms are rare and challenging to treat because of variation in the presenting symptoms and the lack of established management guidelines. We report the case of a patient with a 6-cm-wide giant coronary artery aneurysm that was resected, followed by reconstruction using a saphenous vein graft and 18 years of follow-up.

10.
Polymers (Basel) ; 12(12)2020 Nov 27.
Article in English | MEDLINE | ID: mdl-33261186

ABSTRACT

The intermittent and volatile nature of renewable energy sources threatens the stable operation of power grids, necessitating dynamically operated energy storage. Power-to-gas technology is a promising method for managing electricity variations on a large gigawatt (GW) scale. The electrolyzer is a key component that can convert excess electricity into hydrogen with high flexibility. Recently, organic/inorganic composite separators have been widely used as diaphragm membranes; however, they are prone to increase ohmic resistance and gas crossover, which inhibit electrolyzer efficiency. Here, we show that the ceria nanoparticle and polysulfone composite separator exhibits a low area resistance of 0.16 Ω cm2 and a hydrogen permeability of 1.2 × 10-12 mol cm-1 s-1 bar-1 in 30 wt% potassium hydroxide (KOH) electrolyte, which outperformed the commercial separator, the Zirfon PERL separator. The cell using a 100 nm ceria nanoparticle/polysulfone separator and advanced catalysts has a remarkable capability of 1.84 V at 800 mA cm-2 at 30 wt% and 80 °C. The decrease in the average pore size of 77 nm and high wettability (contact angle 75°) contributed to the reduced ohmic resistance and low gas crossover. These results demonstrate that the use of ceria nanoparticle-based separators can achieve high performance compared to commercial zirconia-based separators.

11.
Korean J Thorac Cardiovasc Surg ; 53(5): 297-300, 2020 Oct 05.
Article in English | MEDLINE | ID: mdl-32919452

ABSTRACT

BACKGROUND: This study aimed to assess the effect of vessel size and flow characteristics on the maturation of autogenous radiocephalic arteriovenous fistulae (RCAVFs). METHODS: We retrospectively reviewed records of patients undergoing RCAVF creation at a single medical center from January 2013 to December 2019. Operative variables were compared between patients whose fistulae matured and those whose fistulae failed to mature. RESULTS: Overall, 152 patients (33 of whom were women) with a mean age of 62.6±13.6 years underwent RCAVF creation; functional maturation was achieved in 123. No statistically significant differences were observed between patients in whom maturation was or was not achieved in terms of the following variables: female sex (20.3% vs. 25.0%), radial artery size (2.5 vs. 2.4 mm), and pulsatility index (0.69 vs. 0.62). Low intraoperative transit time flowmetry (TTF; 150.4 vs. 98.1 mL/min) and small vein size (2.4 vs. 2.0 mm) were associated with failure of maturation. The best cutoff diameter for RCAVF TTF and cephalic vein size were 105 mL/min and 2.45 mm, respectively. CONCLUSION: In patients who undergo RCAVF creation, vein diameter on preoperative ultrasonography and intraoperative TTF are predictors of functional maturation. We identified an intraoperative TTF cutoff value that can be used for intraoperative decision-making.

12.
Korean J Thorac Cardiovasc Surg ; 52(1): 25-31, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30834214

ABSTRACT

BACKGROUND: The primary goal of this study was to characterize the clinical outcomes of adult patients with hematologic malignancies (HM) who were treated with extracorporeal membrane oxygenation (ECMO) support when conventional treatments failed. METHODS: In this retrospective, observational study at a tertiary medical center, we reviewed the clinical course of 23 consecutive patients with HM requiring ECMO who were admitted to the intensive care unit at Asan Medical Center from March 2010 to April 2015. RESULTS: A total of 23 patients (8 female; median age, 44 years; range, 29-51 years) with HM and severe acute circulatory and/or respiratory failure received ECMO therapy during the study period. Fourteen patients received veno-arterial ECMO, while 9 patients received veno-venous ECMO. The median ECMO duration was 104.7 hours (range, 37.1-221 hours). Nine patients were successfully weaned from ECMO. The in-hospital mortality rate was 91.1% (21 of 23). There were complications in 3 patients (cannulation site bleeding, limb ischemia, and gastrointestinal bleeding). CONCLUSION: ECMO is a useful treatment for patients with circulatory and/or pulmonary failure. However, in patients with HM, the outcomes of ECMO treatment results were very poor, so it is advisable to carefully decide whether to apply ECMO to these patients.

13.
Korean J Thorac Cardiovasc Surg ; 51(6): 376-383, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30588445

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the outcomes of surgical resection in patients with radiographically noninvasive lung adenocarcinoma according to the surgical strategy. METHODS: A retrospective study was conducted of 128 patients who underwent pulmonary resection for ground-glass opacity (GGO)-dominant nodules measuring ≤2 cm with a consolidation/tumor ratio ≤0.25 based on computed tomography between 2008 and 2015. The 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate were analyzed. RESULTS: Among the 128 patients, wedge resection, segmentectomy, and lobectomy were performed in 40 (31.2%), 22 (17.2%), and 66 patients (51.6%), respectively. No significant differences were found among the groups in the mean size of tumors (p=0.119), the rate of pure-GGO nodules (p=0.814), the consolidation/tumor ratio (p=0.695), or the rate of invasive adenocarcinoma (p=0.378). Centrally located tumors were more common in the lobectomy group (21.2%) than in the wedge resection (0%) or segmentectomy (0%) groups (p=0.001). There were no significant differences in the 5-year DFS rate (100%, 100%, 92.7%, respectively; p=0.76) or 5-year OS rate (100%, 100%, 100%; p=0.223) among the wedge resection, segmentectomy, and lobectomy groups. CONCLUSION: For radiographically noninvasive lung adenocarcinoma measuring ≤2 cm with a consolidation/tumor ratio ≤0.25, wedge resection and segmentectomy could be comparable surgical options to lobectomy.

14.
Korean J Thorac Cardiovasc Surg ; 51(6): 399-402, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30588449

ABSTRACT

A 61-year-old woman who presented with claudication and dyspnea on exertion was found to have severe calcified narrowing of the descending aorta and severe insufficiency of the aortic valve. These findings were compatible with Takayasu arteritis. To treat these hemodynamic abnormalities, extra-aortic bypass surgery combined with replacement of the aortic valve and ascending aorta-to-hemiarch replacement was performed through a separated upper hemi-sternotomy and limited median laparotomy. We present our successful surgical experience with this case.

15.
Nano Lett ; 16(11): 7261-7269, 2016 11 09.
Article in English | MEDLINE | ID: mdl-27775893

ABSTRACT

Nanostructured silicon (Si) is useful in many applications and has typically been synthesized by bottom-up colloid-based solution processes or top-down gas phase reactions at high temperatures. These methods, however, suffer from toxic precursors, low yields, and impractical processing conditions (i.e., high pressure). The magnesiothermic reduction of silicon oxide (SiO2) has also been introduced as an alternative method. Here, we demonstrate the reduction of SiO2 by a simple milling process using a lab-scale planetary-ball mill and industry-scale attrition-mill. Moreover, an ignition point where the reduction begins was consistently observed for the milling processes, which could be used to accurately monitor and control the reaction. The complete conversion of rice husk SiO2 to high purity Si was demonstrated, taking advantage of the rice husk's uniform nanoporosity and global availability, using a 5L-scale attrition-mill. The resulting porous Si showed excellent performance as a Li-ion battery anode, retaining 82.8% of the initial capacity of 1466 mAh g-1 after 200 cycles.

16.
Korean J Thorac Cardiovasc Surg ; 49(5): 356-360, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27733995

ABSTRACT

BACKGROUND: The standard approach in treating cardiac myxoma is the median full sternotomy. With the evolution of surgical techniques, the right minithoracotomy approach has emerged as an alternative method. Since few studies have been published assessing the right minithoracotomy approach, we performed a retrospective study to compare the clinical outcomes of the right minithoracotomy approach with those of the sternotomy approach. METHODS: From January 2005 to December 2014, 203 patients underwent resection of a cardiac myxoma. Patients with preexisting cardiac problems were excluded from this study. 146 patients were enrolled in this study; 83 patients were treated using a median sternotomy and 63 patients were treated using a right minithoracotomy. RESULTS: No early mortalities were recorded in either group. Although the cardiopulmonary bypass time and aorta cross-clamp time were significantly shorter in the sternotomy group (p<0.001 and p=0.005), postoperative blood transfusions and arrhythmia events were significantly less common in the thoracotomy group (p=0.004 and p=0.025, respectively). No significant differences were found in the duration of the hospital stay, postoperative intubation time, the duration of the intensive care unit stay, and recurrence. CONCLUSION: The minimally invasive right minithoracotomy approach is a good alternative method for treating cardiac myxoma because it was found to be associated with a lower incidence of postoperative complications and a shorter postoperative recovery period.

17.
Korean J Thorac Cardiovasc Surg ; 49(5): 397-400, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27734003

ABSTRACT

Essential thrombocytosis (ET) is a myeloproliferative disorder characterized by an anomalous increase in platelet production. Many patients with ET are asymptomatic. Few studies have reported ET-associated thromboembolism in large vessels such as the aorta. We report a patient with ET who presented with peripheral embolism from an abdominal aortic thrombus and developed acute limb ischemia. The patient underwent aortic replacement successfully. The patient's platelet count was controlled with hydroxyurea, and no recurrence was noted over 2 years of follow-up.

18.
Eur J Cardiothorac Surg ; 49(3): 818-22, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25943874

ABSTRACT

OBJECTIVES: Pericardial effusion can cause haemodynamic compromise after heart transplantation. We identified the effects of soft drains on the development of pericardial effusion. METHODS: We enrolled 250 patients ≥17 years of age who underwent heart transplantation between July 1999 and April 2012 and received two conventional tubes (n = 96; 32 French), or two tubes with a soft drain (n = 154; 4.8 mm wide). The development of significant pericardial effusion or the need for drainage procedure during 1 month after heart transplantation was compared with the use of the propensity score matching method to adjust for selection bias. RESULTS: At 1 month after transplantation, 69 patients (27.6%) developed significant pericardial effusion. Among these, 13 patients (5.2%) underwent pericardial drainage. According to multivariate analysis, history of previous cardiac surgery [odds ratio (OR) = 0.162; 95% confidence interval (CI) = 0.046-0.565; P = 0.004] and placement of a soft drain (OR = 0.186; 95% CI = 0.100-0.346; P < 0.001) were significant factors that prevented pericardial effusion or the need for drainage during the early postoperative period. For the 82 propensity score matched pairs, patients receiving an additional soft drain were at a lower risk of the development of significant pericardial effusion or the need for a pericardial drainage procedure during 1 month (OR = 0.148; 95% CI = 0.068-0.318; P < 0.001) compared with those receiving only two conventional tubes. CONCLUSIONS: Pericardial soft drainage is a simple and safe procedure that reduces pericardial effusion and decreases the need for pericardial drainage after heart transplantation.


Subject(s)
Drainage/instrumentation , Drainage/statistics & numerical data , Heart Transplantation/adverse effects , Pericardial Effusion/epidemiology , Postoperative Complications/epidemiology , Adult , Drainage/methods , Female , Humans , Male , Middle Aged , Pericardial Effusion/prevention & control , Postoperative Complications/prevention & control , Retrospective Studies , Risk Factors
19.
J Card Surg ; 30(11): 869-71, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26347383

ABSTRACT

Ewing's sarcoma is a histological type of malignant mesenchymal tumor and rarely originates from the heart. We report a case of Ewing's sarcoma located in the right ventricular outflow tract that invaded the left pulmonary vein in a 29-year-old female.


Subject(s)
Blood Vessel Prosthesis Implantation/methods , Heart Neoplasms/surgery , Heart Transplantation/methods , Heart Ventricles , Pulmonary Veins/surgery , Sarcoma, Ewing/surgery , Vascular Neoplasms/surgery , Adult , Female , Heart Neoplasms/pathology , Humans , Neoplasm Invasiveness , Sarcoma, Ewing/pathology , Treatment Outcome , Vascular Neoplasms/pathology
20.
Bioorg Med Chem ; 23(20): 6673-82, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26386817

ABSTRACT

We synthesized a library of curcumin mimics with diverse alkylsulfonyl and substituted benzenesulfonyl modifications through a simple addition reaction of important intermediate, 1-(3-Amino-phenyl)-3-(4-hydroxy-3-methoxy-phenyl)-propenone (10), with various sulfonyl chloride reactants and then tested their vasodilatation effect on depolarization (50 mM K(+))- and endothelin-1 (ET-1)-induced basilar artery contraction. Generally, curcumin mimics with aromatic sulfonyl groups showed stronger vasodilation effect than alkyl sulfonylated curcumin mimics. Among the tested compounds, six curcumin mimics (11g, 11h, 11i, 11j, 11l, and 11s) in a depolarization-induced vasoconstriction and seven compounds (11g, 11h, 11i, 11j, 11l, 11p, and 11s) in an ET-1-induced vasoconstriction showed strong vasodilation effect. Based on their biological properties, synthetic curcumin mimics can act as dual antagonist scaffold of L-type Ca(2+) channel and endothelin A/B2 receptor in vascular smooth muscle cells. In particular, compounds 11g and 11s are promising novel drug candidates to treat hypertension related to the overexpression of L-type Ca(2+) channels and ET peptides/receptors-mediated cardiovascular diseases.


Subject(s)
Calcium Channel Blockers/pharmacology , Curcumin/pharmacology , Endothelin A Receptor Antagonists/pharmacology , Endothelin B Receptor Antagonists/pharmacology , Animals , Calcium Channel Blockers/chemical synthesis , Calcium Channel Blockers/chemistry , Calcium Channels, L-Type/metabolism , Curcumin/chemical synthesis , Curcumin/chemistry , Dose-Response Relationship, Drug , Endothelin A Receptor Antagonists/chemical synthesis , Endothelin A Receptor Antagonists/chemistry , Endothelin B Receptor Antagonists/chemical synthesis , Endothelin B Receptor Antagonists/chemistry , Male , Molecular Structure , Rabbits , Receptor, Endothelin A/metabolism , Receptor, Endothelin B/metabolism , Structure-Activity Relationship
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