Characteristics of gastrointestinal stromal tumor (GIST) patients receiving short-term versus long-term imatinib (IM) adjuvant therapy: A chart review analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10094-10094
Author(s):  
Annie Guerin ◽  
Anthony Paul Conley ◽  
Medha Sasane ◽  
Genevieve Gauthier ◽  
Frances Schwiep ◽  
...  
Keyword(s):  
Heart Diseases ◽  
Clinical Information ◽  
Extended Period ◽  
Risk Profile ◽  
Prescribing Patterns ◽  
Short Term ◽  
Online Data ◽  
Chi Square ◽  
Post Surgery

10094 Background: In clinical practice, significant variability is seen in duration of adjuvant IM use. The objective of this study is to compare characteristics of GIST pts receiving adjuvant IM for a short (6-12 months) vs extended period (≥24 months) to better understand factors that may influence treatment (trt) duration decisions. Methods: Physician prescribing patterns and clinical information on adult pts with primary resectable Kit positive GIST initiating IM ≤84 days post-surgery was collected from 248 U.S. oncologists using online data collection forms. In addition to physicians’ perception of short- vs long-term use, pts’ risk assessment, trt, demographics, and comorbidities were collected for 246 short-term and 395 long-term IM pts. Characteristics were compared using Wilcoxon and Chi-square tests. Results: While pts were similar in age [59.0 vs. 58.1, P =.23], ethnicity, and region of residence, the short-term group included fewer males (57.7% vs 69.6%, P <.01) and had a higher prevalence of cardiovascular (11.4% vs 5.8%, P = .01) and ischemic heart diseases (5.3% vs 1.5%, P<.01). Differences were also observed in indicators of pre-treatment risk profile (tumor size, location, and rupture during surgery, mitotic count, and Miettinen score) (Table). Findings were consistent with main reasons reported by physicians for prescribing adjuvant IM over longer duration; in addition to pt risk profile (76.6%), tolerability (70.6%), younger pts (59.7%), safety (39.1%), trt response (29.8%), and economic reasons (26.2%) were other reasons impacting trt decisions. Conclusions: Pt risk is an important factor in physicians’ decisions to prescribe adjuvant IM for extended duration. However, age, tolerability, and comorbidities, also play an important role. [Table: see text]

Investigation of gastrointestinal stromal tumor (GIST) care management in GIST patients (pts) receiving short-term versus long-term imatinib (IM) adjuvant therapy: A chart review analysis.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 195-195
Author(s):  
Anthony Paul Conley ◽  
Annie Guérin ◽  
Medha Sasane ◽  
Geneviève Gauthier ◽  
Frances Schwiep ◽  
...  
Keyword(s):  
Risk Assessment ◽  
High Risk ◽  
Risk Profile ◽  
Prescribing Patterns ◽  
Community Practice ◽  
Short Term ◽  
Online Data ◽  
Kit Mutation ◽  
Nccn Guidelines

195 Background: Although optimal duration of adjuvant IM therapy in Kit+ GIST pts is unknown, the NCCN guidelines recommend treatment for ≥36 months in high-risk pts based on clinical trials showing reduced risk of recurrence and mortality in pts receiving long-term adjuvant IM. The objective of this study was to investigate clinicians’ recurrence risk assessment and GIST management in patients receiving adjuvant IM for short- (6-12 months) vs. long-term (≥24 months) in community practice. Methods: GIST-related and treatment characteristic information on adult pts with primary resectable Kit+ GIST initiating IM ≤84 days after surgery (short-term: 411 pts; long-term: 408 pts) was collected from 320 U.S. oncologists using an online data collection form. In addition, physician prescribing patterns and perception of risk assessment and IM duration were collected. Results: Indicators of risk (tumor size, mitotic count, and tumor location) were significantly associated with IM treatment duration. Tumor rupture status did not impact IM duration, except when unknown, in which case pts had longer IM duration. About 50% of pts had not been tested for Kit mutation; 31% of physicians reported that it would not have changed therapy/management or were not aware of how results should have impacted GIST management. Among short-term pts for whom physicians reported a reason for IM discontinuation, main reasons included non-severe adverse events, completion of the 1-year treatment scheduled, economic constraint/health plan coverage change, and pts’ preference. Overall, 77.8% of surveyed physicians reported that pt risk profile drove their decision of continuing IM over an extended period of time. However, in practice 39.9% of the short-term pts and 48.8% of the long-term pts had a high risk profile as assessed by Fletcher classification; suggesting a lack of consistency between treatment related opinions and practice. Conclusions: These observed discrepancies highlight the need for standardization of risk assessment practices and education among community oncologists and pts.

Risk of disease recurrence and mortality in gastrointestinal stromal tumor (GIST) patients receiving short-term versus long-term imatinib adjuvant therapy: A chart review analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e20511-e20511
Author(s):  
Anthony Paul Conley ◽  
Annie Guerin ◽  
Medha Sasane ◽  
Genevieve Gauthier ◽  
Frances Schwiep ◽  
...  
Keyword(s):  
Extended Period ◽  
Disease Recurrence ◽  
Mortality Rates ◽  
Short Term ◽  
Online Data ◽  
Risk Of Recurrence ◽  
Adjusted Risk ◽  
Risk Of Disease ◽  
Collection Form

e20511 Background: The benefits of long-term (36 months) use of adjuvant imatinib (IM) in high risk GIST patients (pts) have been demonstrated in a recent multicenter, prospective clinical trial that compared efficacy and safety of 3 years vs 1 year IM treatment. However, in clinical practice, there is no consensus on the optimal IM treatment duration after surgery. The objective of this retrospective observational study was to compare the risk of recurrence and survival among primary resectable Kit positive GIST pts treated with adjuvant IM for a short vs an extended period of time in a real-world setting. Methods: Information on adult pts with primary resectable Kit positive GIST initiating imatinib ≤84 days after surgery was collected from 248 U.S. oncologists using an online data collection form. Detailed pt information following first GIST diagnosis, including demographic, GIST-related characteristics (e.g., risk profile), comorbidity profile, IM treatment characteristics, disease recurrence and mortality was collected for pts with short-term (6-12 months) and long-term IM use (≥24 months). Disease recurrence and mortality rates were estimated from the 1st surgery date to the 1st evidence of recurrence, mortality, or end of observation period. Multivariate Cox proportional hazard models were used to compare recurrence and mortality rates between short vs long term IM use pts. Results: Among the 246 short-term and 395 long-term IM pts, the median follow up was 884 and 963 days, respectively. The average age was similar [59.0 (10.4) vs 58.1 (9.5); p=.23] but short-term pts had less males [57.7% vs 69.6% (p<.01)] and a lower Miettinen risk score [0.3 vs 0.4, p< .01)] than long-term pts. Disease recurrence [7.3 vs 1.8%, (p< .01)] and mortality rates [6.9% vs 2.3%, (p < .01)] were also higher in short- vs long-term pts. The adjusted risk of recurrence was 4.77 times [95% CI: 1.98 – 11.48, (p<.01)] higher and mortality risk was 3.44 times [CI: 1.53 – 7.75, (p<.01)] higher in short- vs long-term pts. Conclusions: Use of IM over an extended period of time is associated with a reduction in long-term risk of disease recurrence and mortality.

Abstract 84: Late (5-20 Years) Outcome After STA-MCA Anastomosis and Ultimate Indirect Bypass in Patients With Moyamoya Disease

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Satoshi Kuroda ◽  
Naoki Nakayama ◽  
Shusuke Yamamoto ◽  
Daina Kashiwazaki ◽  
Haruto Uchino ◽  
...  
Keyword(s):  
Disease Progression ◽  
Moyamoya Disease ◽  
Hemorrhagic Stroke ◽  
Short Term ◽  
Post Surgery ◽  
Initial Surgery ◽  
Cerebrovascular Events ◽  
Late Morbidity

Background and Purpose: Surgical revascularization is now known to improve the outcome in patients with moyamoya disease. However, majority of previous studies reported their short-term (<5 years) outcome. Therefore, this study was aimed to evaluate long-term (5 to 20 years) outcome after STA-MCA anastomosis and ultimate indirect bypass, encephalo-duro-myo- arterio-pericranial synangiosis (EDMAPS). Methods: Cumulative incidence of late morbidity/mortality and disease progression were evaluated among 93 patients who underwent STA-MCA anastomosis and EDMAPS. All of them were prospectively followed up for longer than 5 years post-surgery (mean, 10.5±4.4 years). There were 35 pediatric and 58 adult patients. Clinical diagnosis included TIA or ischemic stroke in 80 patients, hemorrhagic stroke in 10, and asymptomatic in 3. STA-MCA anastomosis and EDMAPS were performed onto their 141 hemispheres. MRI and MRA were performed every 6 or 12 years during follow-up periods. Results: During follow-up periods, 92/93 patients were free from any stroke or death, but one recurred hemorrhagic stroke (0.10% per patient-year). Disease progression occurred in the territory of the contralateral carotid or posterior cerebral artery (PCA) in 19 hemispheres of 15 patients (1.5% per patient-year). The interval between initial surgery and disease progression varied from 0.5 to 15 years. Repeat bypass surgery for anterior and posterior circulations resolved ischemic attacks in all 10 patients. Conclusion: STA-MCA anastomosis and EDMAPS would be the best choice to prevent further cerebrovascular events for longer than 10 years by widely providing surgical collaterals to both the MCA and ACA territories. However, regular follow-up would be essential for longer than 10 years post-surgery to identify the disease progression in the territory of contralateral carotid artery and PCA and prevent late cerebrovascular events.

Does meloxicam provide adequate pain management as a post-operative analgesic in canine ovariohysterectomy patients?

2020 ◽  
Vol 11 (4) ◽  
pp. 192-197
Author(s):  
Gavin Goldsbrough ◽  
Helen Reynolds
Keyword(s):  
Pain Management ◽  
Pain Score ◽  
Pain Scale ◽  
Short Term ◽  
Post Surgery ◽  
Pain Scores ◽  
Significant Difference ◽  
Time Frames ◽  
Adequate Pain Management

Background: Meloxicam is an analgesic agent with anti-inflammatory properties, commonly used in veterinary practices to treat a variety of different long-term medical conditions and is also used as a short-term pain relief following particularly traumatic surgeries. Aims: An observational study was conducted to determine whether meloxicam provides adequate pain management as a post-operative analgesic for canine ovariohysterectomies. Methods: 13 canines were admitted for ovariohysterectomy. Each patient was assessed using the Glasgow composite pain scale (CMPS) prior to surgery during the admission procedure, 15 minutes post-operatively, at discharge and at their post-operative check (POC) 3–5 days after surgery. Results: Data were statistically analysed to determine the overall effectiveness of meloxicam in reducing pain following canine ovariohysterectomy. The results showed a statistically significant difference (Kruskal-Wallis test: H3 =12.98, p=0.005) in pain scores between admission, 15 minutes post operatively, discharge and 3–5 days POC. The greatest decrease in pain score was between 15 minutes post-operatively and POC (Mann-Whitney U test: W=236, n=13, 13, p=0.0014) and between discharge and POC (Mann-Whitney U test: W=227, n=13, 13, p=0.0060). Overall, this demonstrated that there was an improvement in pain suggesting meloxicam is effective between these time frames. In addition, 69.2% (n=9) of patients in the study showed a pain score of 0, indicating an absence of pain, on their final POC. Statistical analysis was also used to determine if there was any difference in pain score between the 3, 4 or 5 day POC pain score. The results show there was no significant difference (Kruskal-Wallis test: H2 =0.090, p=0.638) suggesting that meloxicam's effectiveness was similar across this range of time post surgery. Conclusion: The results from the study indicate that meloxicam is an effective post-operative analgesic for canine patients undergoing an ovariohysterectomy.

scholarly journals Did the introduction and increased prescribing of antidepressants lead to changes in long-term trends of suicide rates?

2020 ◽  
Author(s):  
Simone Amendola ◽  
Martin Plöderl ◽  
Michael P Hengartner
Keyword(s):  
General Pattern ◽  
Extended Period ◽  
Joinpoint Regression ◽  
Short Term ◽  
Term Study ◽  
Suicide Rates ◽  
Long Term Study ◽  
Prescription Rates ◽  
Long Term Trends

Abstract Background Ecological studies have explored associations between suicide rates and antidepressant prescriptions in the population, but most of them are limited as they analyzed short-term correlations that may be spurious. The aim of this long-term study was to examine whether trends in suicide rates changed in three European countries when the first antidepressants were introduced in 1960 and when prescription rates increased steeply after 1990 with the introduction of the serotonin reuptake inhibitors (SSRIs). Methods Data were extracted from the WHO Mortality Database. Suicide rates were calculated for people aged 10–89 years from 1951–2015 for Italy, 1955–2016 for Austria and 1951–2013 for Switzerland. Trends in suicide rates stratified by gender were analyzed using joinpoint regression models. Results There was a general pattern of long-term trends that was broadly consistent across all three countries. Suicide rates were stable or decreasing during the 1950s and 1960s, they rose during the 1970s, peaked in the early 1980s and thereafter they declined. There were a few notable exceptions to these general trends. In Italian men, suicide rates increased until 1997, then fell sharply until 2006 and increased again from 2006 to 2015. In women from all three countries, there was an extended period during the 2000s when suicide rates were stable. No trend changes occurred around 1960 or 1990. Conclusions The introduction of antidepressants around 1960 and the sharp increase in prescriptions after 1990 with the introduction of the SSRIs did not coincide with trend changes in suicide rates in Italy, Austria or Switzerland.

scholarly journals The Clinical Effectiveness and Cost Effectiveness of Bariatric Metabolic Surgery for Obese with Poorly Controlled Type 2 Diabetes Patients In Malaysia - A Study Protocol

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1634-1634
Author(s):  
Jo Ann Galvan ◽  
Karuthan Chinna ◽  
Rusli Nordin ◽  
Nik Kosai Mahmood ◽  
Chin Kin Fah ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Cost Effectiveness ◽  
Study Protocol ◽  
Diabetes Care ◽  
Clinical Effectiveness ◽  
Term Effect ◽  
Short Term ◽  
Post Surgery ◽  
Obesity And Diabetes

Abstract Objectives Bariatric Surgery is a major breakthrough in diabetes care. Complete remission is attainable in a great percentage of patients. However, there is slow progress in this procedure in Malaysia. With the overwhelming rate of obesity and diabetes in the country, the potential advantage of this treatment modality is underestimated. Conventional diabetes care only controls 22% of the diabetics and healthcare expenditure has ballooned due to complications costs amounting to at least RM 2 billion in a year eating up 10% of the government's budget on healthcare. Furthermore, this burden will increase in the next decades as diabetes is predicted to increase by 69% by 2030. While this procedure is beneficial, it is an expensive intervention with risks of complications. This raises the question of whether bariatric surgery is cost-effective in the context of this country? Evidence must be available to decision-makers weighing the risk-benefit ratio of the procedure. This study aims to assess the clinical effectiveness and cost-effectiveness of bariatric surgery in managing obesity among the Malaysian population. It will specifically investigate the short term and long-term effects of the procedure investigating anthropometric and metabolic disease blood indicator changes while assessing direct, indirect costs, QALYs gained and complications associated with the procedure. Methods We will review charts of all patients who have undergone bariatric surgery procedures from 2014 to 2016 in HUKM, Department of Surgery and in Andrea Bariatric Surgery Clinic. We will look at their weight, BMI, and some blood parameter results before and after surgery one-year post-surgery for the short-term effect and 3–5 years post-surgery for the long-term effect. We will also assess the mortality risks and complications of the procedures. Study Population: All patients who underwent Bariatric Surgery procedures from 2014–206 in HUKM and in Andrea Bariatric Surgery ClinicStudy Site/Location: HUKM, Department of Surgery & Andrea Bariatric Surgery Clinic Results N/A - Study Protocol Conclusions The result of this study can contribute to the decision making of patients, doctors, and Health Insurance Companies in Malaysia Funding Sources Center for Research Management, Taylor's University.

Splenectomy in Patients with Myeloproliferative Neoplasms (MPNs): Efficacy, Complications and Impact On Survival and Transformation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2853-2853
Author(s):  
Fabio P S Santos ◽  
Constantine S. Tam ◽  
Hagop M. Kantarjian ◽  
Jorge E. Cortes ◽  
Deborah A. Thomas ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Therapeutic Option ◽  
Splenic Vein ◽  
Time Dependent ◽  
Chromosome 17 ◽  
Short Term ◽  
Post Surgery ◽  
Impact On Survival ◽  
Md Anderson

Abstract Abstract 2853 Introduction: Splenectomy may be an effective therapeutic option for treating massive splenomegaly in patients with MPNs. There is still limited data on its short- and long-term benefits and risks. Objective: To describe short-term outcomes, complications and impact on survival and transformation to acute myeloid leukemia (AML) in patients with MPNs who underwent splenectomy. Methods: First, efficacy and short-term complications were analyzed in 94 patients with different MPNs who underwent splenectomy at MD Anderson between 1981–2009. Second, medical records of 696 patients with myelofibrosis (MF) seen at MD Anderson between 1966–2009 were reviewed (among which 91 underwent splenectomy either at or outside MD Anderson) to evaluate the long-term impact of splenectomy on overall survival (OS) and transformation-free survival (TFS). Improvement in anemia and thrombocytopenia were defined by the International Working Group on Myelofibrosis Research and Treatment response criteria. Survival was estimated by Kaplan-Meier method, and hazard ratios (HR) were determined by Cox multivariate analysis. Splenectomy was analyzed as a time-dependent covariate. Risk in patients with MF was determined by the Dynamic International Prognostic Scoring System (DIPSS). Accelerated phase (AP) criteria in MF were determined as thrombocytopenia <50×109/L, chromosome 17 abnormalities and blasts >10% in peripheral blood (PB) or bone marrow (BM). Results: Splenectomy improved spleen pain, anemia and thrombocytopenia in 84%, 47% and 66% of patients, respectively. Among patients with MF, improvement in anemia and thrombocytopenia was seen in 44% and 75% of patients, respectively. Hematological complications included post-operative leukocytosis (76%) and thrombocytosis (43%), developing within a median time of 1 day and 5 days post-surgery, respectively. Early (<7 days) intervention for control of elevated white blood cell and/or platelet count was needed in 37% of patients. Forty-six percent of patients developed non-hematological clinical complications, and the most common was venous thromboembolism (VTE; 16%). VTE sites included portal vein (N=11), supra-hepatic vein (N=3) and superior vena cava, pulmonary embolism and splenic vein (N=1 each). Post-operative mortality was 5%. Median survival post-splenectomy was 19.2 months, and 5-year survival 16.1%. In the second cohort of patients with MF, requirement for splenectomy was associated with decreased OS (HR=2.84, p<0.0001) and TFS (HR=2.79, p<0.0001). In the multivariable model, the time dependent covariate splenectomyremained an independent risk factor for inferior OS and TFS in patients with MF, alongside male sex, transfusion dependency, DIPSS score and AP criteria (Table). Conclusions: Splenectomyis a possible therapeutic option for patients with MF and other MPNs, and its greatest benefits are related to improvement in spleen pain and discomfort, anemia and thrombocytopenia. However, in patients with MF it appears to be associated with increased mortality and risk of transformation to AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Minilaparotomy in the treatment of choledochal malformations in children

2021 ◽  
Vol 25 (3) ◽  
pp. 165-173
Author(s):  
A. Yu. Razumovskiy ◽  
Z. B. Mitupov ◽  
N. V. Kulikova ◽  
N. S. Stepanenko ◽  
A. S. Zadvernyuk ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Surgical Techniques ◽  
Clinical Manifestations ◽  
Postoperative Outcomes ◽  
Short Term ◽  
Surgical Time ◽  
Chi Square ◽  
Surgical Interventions ◽  
Mini Laparotomy

Introduction. The article presents the analysis of surgical treatment of children with choledochal malformations (CM) with mini-laparotomy and laparoscopy techniques.Purpose. The aim of the study is to improve outcomes of surgical treatment of choledochal malformations in children.Material and methods. For the last ten years (January 2010 - May 2020), 84 children with choledochal malformations (CM) (n = 84) were operated on with different surgical techniques in our hospitals. Group 1 - patients who had Roux-en-Y hepaticojejunoanastomosis (RYHJ, n = 68, 81%); Group 2 - patients who had hepaticoduodenoanastomosis (HD, n = 16, 19%). The authors compared outcomes because Roux-en-Y hepaticojejunostomosis and hepaticoduodenanastomosis were formed under mini-laparotomic (ML) and laparoscopic (LS) accesses. Surgical time, short-term and long-term postoperative outcomes were assessed.Results. The groups were comparable in gender, age, clinical manifestations, CM complications before surgery, comorbidities (p > 0.05). A statistically significant (p = 0.0000001, Mann–Whitney U-test) decrease in the surgical time was revealed when using mini-laparotomy access. Independent defecation appeared 3 times faster in the subgroup with mini-laparotomy and Roux-en-Y hepaticojejunostomy (ML RYHJ) than in the subgroup of laparoscopic Roux-en-Y hepaticojejunostomy (LS RYHJ) (p = 0.033, Mann–Whitney U-test), mainly due to early enteral loading in the first subgroup (on 0-1 postoperative day). Long-term postoperative outcomes in laparoscopic subgroups revealed a statistically insignificant (p> 0.05) prevalence of 4 anastomotic stenosis requiring repeated surgical interventions. Good outcomes were seen in 90% of patients after ML RYHJ (p = 0.002, Pearson’s Chi-square with Yates’ correction) versus 52.6% after LS RYHJ.Conclusion. Currently, laparoscopy is not a method of choice in children with CM due to the development of short-term and long-term postoperative complications. Minilaparotomy gives promising results in pediatric CM and can be “a gold standard” in the treatment of children with this pathology.

scholarly journals Del Nido vs St Thomas II Cardioplegia in Adult cardiac surgery: A prospective randomized trial of short-term outcomes

2021 ◽  
Author(s):  
Aravind Kalyanasundaram ◽  
Sreevathsa Prasad ◽  
Ram Sankar Padmanabhan ◽  
Hemachandran Munusamy ◽  
Bathal SaiChandran ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Myocardial Protection ◽  
Troponin T ◽  
Adult Population ◽  
Randomized Study ◽  
Short Term ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Post Surgery

Aim/Objective: To assess short term clinical outcomes based on peri-operative troponin T levels (before start of surgery, 2 hours and 12 hours after coming of CPB) of adult patients undergoing cardiac surgery using the del Nido cardioplegia technique compared with st thomas conventional blood cardioplegia Material and method: This was a prospective randomized study with a sample size of 100, which included patients with valvular heart disease requiring single valve replacement in our center from February 2019 to march 2020. Simple randomization technique was used for dividing into two groups of 50 patients each and were given del-nido or st Thomas II cardioplegia accordingly. Perioperative TROPONIN levels, TEE ejection fraction, post-operative inotrope requirement was analyzed. Results: Total of 100 Patients were enrolled in the studie. Mean troponin T immediate post CPB was 559.76 in del nido and 531.14 in blood showing no significance (P 0.146) and 24hrs post-surgery where 290.08 and 231.6 respectively with no significant (0.089) difference. Other parameters like coming of pump need for defibrillation(p-0.629), change in EF measured pre and post CPB (p-0.678) did not show any signifance. Conclusion: Myocardial protection in open cardiac surgery is still evolving. Del-nido cardioplegia is a viable alternative to st thomas cardioplegia which has proven to be statically equivalent in myocardial protection in adult population also. Further studies are required to look into the long-term outcome of use of del nido and to expand the use of del-nido cardioplegia in other adult open cardiac surgeries.

scholarly journals 17β-Estradiol Modulates Expression of Low-Voltage-Activated CaV3.2 T-Type Calcium Channel via Extracellularly Regulated Kinase Pathway in Cardiomyocytes

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 879-888 ◽  
Author(s):  
Farzana Marni ◽  
Yan Wang ◽  
Masaki Morishima ◽  
Toru Shimaoka ◽  
Tomoko Uchino ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Low Voltage ◽  
Heart Diseases ◽  
Ovariectomized Rats ◽  
Pacemaker Activity ◽  
Short Term ◽  
Channel Current ◽  
Long Term Treatment ◽  
17Β Estradiol

T-type Ca2+ channel current (ICa,T) plays an important role for spontaneous pacemaker activity and is involved in the progression of structural heart diseases. Estrogens are of importance for the regulation of growth and differentiation and function in a wide array of target tissues, including those in the cardiovascular system. The aim of this study was to elucidate the short-term and long-term effects of 17β-estradiol (E2) on ICa,T in cardiomyocytes. We employed in vivo and in vitro techniques to clarify E2-mediated modulation of heart rate (HR) in ovariectomized rats and ICa,T in cardiomyocytes. Ovariectomy increased HR and E2 supplement reduced HR in ovariectomized rats. Slowing of E2-induced HR was consistent with the deceleration of automaticity in E2-treated neonatal cardiomyocytes. Short-term application of E2 did not have significant effects on ICa,T, whereas in cardiomyocytes treated with 10 nm E2 for 24 h, estrogen receptor-independent down-regulation of peak ICa,T and declination of CaV3.2 mRNA were observed. Expression of a cardiac-specific transcription factor Csx/Nkx2.5 was also suppressed by E2 treatment for 24 h. On the other hand, expression of CaV3.1 mRNA was unaltered by E2 treatment in this study. An ERK-1/2, 5 inhibitor, PD-98059, abolished the effects of E2 on ICa,T and CaV3.2 mRNA as well as Csx/Nkx2.5 mRNA. These findings indicate that E2 decreases CaV3.2 ICa,T through activation of ERK-1/2, 5, which is mediated by the suppression of Csx/Nkx2.5-dependent transcription, suggesting a genomic effect of E2 as a negative chronotropic factor in the heart. Long-term treatment of cardiomyocytes with 17β-estradiol decreases the T-type Ca2+ channel current of CaV3.2 through activation of ERK-1/2, 5, which is mediated by the suppression of a transcription factor Csx/Nkx2.5.

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