Evaluations of exercise intolerance with cardiopulmonary exercise tests in an 18-year-old adolescent with pituitary stalk interruption syndrome: a case report.

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a rare disease associated with different level of anterior pituitary hormone deficiency resulting with a variety of clinical manifestations which could limit exercise capacity. Cardiopulmonary exercise test (CPET) is valuable in differential diagnosis of exercise intolerance and exercise prescription. CASE PRESENTATION: An 18-year-old male adolescent was diagnosed with PSIS at 4 years old, had undergone growth hormone supplement until puberty, and was referred to rehabilitation department due to exercise intolerance. We arranged pulmonary function test (PFT) and CPET to clarify the cause of limited capacity. The test result provided evidence of moderate functional impairment (54% of predicted maximal oxygen uptake) mainly affected by physical unfitness without significant cardiovascular or pulmonary limitations. CONCLUSION: CPET serves as a valuable tool for diagnostic purpose. Aerobic and resistance exercise training for the patient should be conducted promptly for better prognosis but under safe circumstances, with criteria which could be provided by CPET results.

Serial Cardiopulmonary Exercise Testing in Patients after Extracardiac Conduit Total Cavopulmonary Connection for Single-Ventricle Hearts: An Observational Study.

OBJECTIVE: To analyze the aerobic fitness and evolution of exercise tolerance in patients with single-ventricle physiology after total cavopulmonary connection (TCPC) with an extracardiac conduit (ECC). STUDY DESIGN: This retrospective cohort study included patients with previous ECC-TCPC who underwent cardiopulmonary exercise testing (CPET) between September 2010 and September 2019. Patients who completed at least 2 tests (≥6 months apart) with adequate levels of effort were recruited for the serial CPET evaluation. RESULTS: We identified 70 patients (50% male) with a mean age of 6.45 ± 5.14 years at ECC-TCPC and 15.67 ± 5.03 years at the initial CPET. The peak oxygen consumption (peak VO2) to predicted value (peak PD) was 55.90 ± 16.81%. Twenty of the 70 identified patients (50% male) were recruited for serial analysis. The average number of CPETs was 2.6 per patient. The average duration from the first CPET to the last CPET was 3.64 years. The peak VO2 and PD increased slowly, with mean rates of 38.77 ± 129.01 mL/min and 1.66 ± 6.40%, respectively, during the study period. CONCLUSIONS: Although the patients had lower exercise tolerance after ECC-TCPC compared with their normal peers, exercise tolerance appears to have been preserved over the adolescent period in those who underwent serial testing after ECC-TCPC.

Serial cardiopulmonary exercise testing in an asymptomatic young female receiving percutaneous balloon dilatation for cor triatriatum sinistrum at an early age.

A young female was diagnosed as classic cor triatriatum sinistrum (CTS) at 38 months old incidentally and she received percutaneous catheter-based balloon dilatation twice at 41 and 48 months old. She took regular follow-up by echocardiography biannually with no re-stenosis of the orifice in the membrane between two chambers in the left atrium and she denied any cardiac-related symptoms. Serial cardiopulmonary exercise testing (CPET) by treadmill under Ramped-Bruce protocol was done at her 13, 19, and 23-year old. She could reach maximal effort and complete the three CPETs. No significant change of metabolic equivalent at anaerobic (MET) threshold, peak MET, and pulmonary function were noted in the serial CPETs and all of them were within normal limits comparing to the reference values of Chinese specific to her age. Our case report demonstrated that the concept of percutaneous catheter-based balloon dilatation of obstructive membrane for classic CTS without other associated congenital heart diseases is sound and feasible. The prognosis is well without re-obstruction and the cardiopulmonary fitness after that could be maintain as healthy peers for up to 18 years.

Rehabilitation programs for patients with COronaVIrus Disease 2019: consensus statements of Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation.

The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice.

Early Phase II Comprehensive Cardiac Rehabilitation after Acute Myocardial Infarction.

BACKGROUND: Cardiac rehabilitation is beneficial for patients after ST-segment elevation myocardial infarction (STEMI). However, most institutes perform outpatient training phase (phase II) of post-MI cardiac rehabilitation after 2-4 weeks. To evaluate the possibility of performing cardiac rehabilitation with an earlier schedule after STEMI. METHODS: We conducted a series of early phase II cardiac rehabilitation starting from 5-7 days after STEMI, including the training group (n = 28) and the control group (n = 42). RESULTS: The results showed an improved mental component summary of the SF-36 questionnaire after 6 months in the training group. No adverse event was noticed during this early phase II training. CONCLUSIONS: Cardiac rehabilitation after STEMI might be started earlier than previously thought for clinical use or further research.

Comprehensive Exercise Capacity and Quality of Life Assessments Predict Mortality in Patients with Pulmonary Arterial Hypertension.

BACKGROUND: The 6-minute walk test (6MWT) and cardiopulmonary exercise test (CPET) are exercise tests associated with physical function, quality of life and hemodynamic data in patients with pulmonary arterial hypertension (PAH). This study was conducted to assess correlations between exercise capacity, quality of life and disease functional classification, and to analyze the value of comprehensive assessments in predicting mortality in patients with PAH. METHODS: Fifty-four patients with PAH were enrolled. Comprehensive assessments including exercise capacity evaluated using the 6MWT and CPET, and health-related quality of life evaluated using the Short Form 36 (SF-36) questionnaire were performed in all participants. The patients were followed for 2 years with the end point of mortality. RESULTS: The survivors had a longer 6-minute walking distance, higher peak oxygen uptake and higher physical component score of the SF-36 than the non-survivors. In addition, exercise capacity combined with SF-36 predicted 2-year mortality in the patients with PAH. The patients with lower peak oxygen uptake (peak VO2 < 11.03 mL/kg/ min) and lower physical component score (score < 44.54) had a higher mortality rate than those with a higher peak VO2 and higher physical component score (adjusted hazard ratio = 19.95, p = 0.011). CONCLUSIONS: Comprehensive assessments of exercise capacity and quality of life can be used to predict 2-year mortality in patients with PAH.

Analysis of Exercise Capacity of Children with Kawasaki Disease by a Coronary Artery z Score Model (ZSP Version 4) Derived by the Lambda-Mu-Sigma Method.

OBJECTIVE: To compare exercise capacity measured by direct cardiopulmonary exercise testing (CPET) of children with Kawasaki disease with different coronary artery diameter z scores (CA z score). STUDY DESIGN: This was a retrospective study that recruited children with Kawasaki disease after the acute stage receiving CPETs determined by CPET with treadmill. CA z score was based on a model using the Lambda-Mu-Sigma method. Max-Z was defined as the maximum z score of the proximal left anterior descending CA (LCA) or right CA (RCA). Children with Kawasaki disease with a Max z <2.0 and ≥2.0 were defined as Kawasaki disease group 1 and Kawasaki disease group 2, respectively. RESULTS: We recruited 32 boys and 17 girls with a mean age of 12.39 ± 3.61 years. Kawasaki disease group 1 (n = 36) had significantly higher peak metabolic equivalent (peak-MET) and peak rate pressure product (PRPP) than Kawasaki disease group 2 (n-13) (P = .046, P < .001). Max-Z correlated with peak-MET moderately and negatively (P < .001, Spearman rho= - .506). Max-Z correlated with PRPP modestly and negatively (P = .011, Spearman rho= - .360). CONCLUSIONS: Children after Kawasaki disease with a coronary artery Max-Z ≥ 2.0 had significantly lower peak exercise capacity than those with a Max-Z < 2.0. Max-Z might be used as an indicator of CA reserve and exercise capacity during peak exercise after the acute stage of Kawasaki disease.

Exploration of Niflumic Acid's Action on Ca²âº Movement and Cell Viability in Human Osteosarcoma Cells.

Niflumic acid, a drug used for joint and muscular pain, affected Ca²âº signaling in different models. However, the effect of niflumic acid on Ca²âº homeostasis and Ca²âº-related physiology in human osteosarcoma cells is unknown. This study examined the effect of niflumic acid on cytosolic free Ca²âº concentrations ([Ca²âº]i) in MG63 human osteosarcoma cells. Intracellular Ca²âº concentrations in suspended cells were monitored by using the fluorescent Ca²âº-sensitive dye fura- 2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio- 1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). In MG63 cells, niflumic acid at concentrations of 250-750 µM evoked [Ca²âº]i rises concentration-dependently. Niflumic acid-evoked Ca²âº entry was confirmed by Mn²âº-induced quenching of fura-2 fluorescence. This entry was inhibited by nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA), but was not affected by the PKC inhibitor GF109203X. In Ca²âº- free medium, treatment with the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin (TG) inhibited niflumic acid-evoked [Ca²âº]i rises. Conversely, treatment with niflumic acid abolished TG-evoked [Ca²âº]i rises. Inhibition of phospholipase C (PLC) with U73122 also partly reduced niflumic acid-evoked [Ca²âº]i rises. Niflumic acid killed cells at 200-500 µM in a concentration-dependent fashion. Chelating cytosolic Ca²âº with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/ AM (BAPTA/AM) did not reverse niflumic acid-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, niflumic acid induced [Ca²âº]i rises by evoking PLC-dependent Ca²âº release from the endoplasmic reticulum, and Ca²âº entry via PKC-sensitive store-operated Ca²âº entry. Niflumic acid also induced Ca²âº-independent cell death.

Effect of thymol on Ca²âº homeostasis and viability in PC3 human prostate cancer cells.

Thymol is a phenolic compound that affects physiology in different cell models. However, whether thymol affects Ca²âº homeostasis in prostate cancer cells is unknown. The action of this compound on cytosolic Ca²âº concentrations ([Ca²âº]i) and viability in PC3 human prostate cancer cells was explored. The results show that thymol at concentrations of 100-1500 µM caused [Ca²âº]i rises in a concentration-dependent manner. Removal of extracellular Ca²âº reduced thymol's effect by approximately 80%. Thymol-induced Ca²âº entry was confirmed by Mn²âº entry-induced quench of fura-2 fluorescence, and was inhibited by approximately 30% by Ca²âº entry modulators (nifedipine, econazole, SKF96365), and the protein kinase C (PKC) inhibitor GF109203X. In Ca²âº-free medium, treatment with the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin abolished thymol-induced [Ca²âº]i rises. Treatment with thymol also abolished thapsigargin-induced [Ca²âº]i rises. Thymol-induced Ca²âº release from the endoplasmic reticulum was abolished by the phospholipase C (PLC) inhibitor U73122. Thymol at 100-900 µM decreased cell viability, which was not reversed by pretreatment with the Ca²âº chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in PC3 cells, thymol induced [Ca²âº]i rises by inducing PLC-dependent Ca²âº release from the endoplasmic reticulum and Ca²âº entry via PKC-sensitive store-operated Ca²âº channels and other unknown channels. Thymol also induced Ca²âº-dissociated cell death.

Effect of protriptyline on [Ca2+]i and viability in MG63 human osteosarcoma cells.

Tricyclic antidepressants (TCA) have been clinically prescribed in the auxiliary treatment of cancer patients. Although protriptyline, a type of TCA, was used primarily in the clinical treatment of mood disorders in cancer patients, the effect of protriptyline on physiology in human osteosarcoma is unknown. This study examined the effect of protriptyline on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Protriptyline between 50 and 250 µM evoked [Ca2+]i rises concentration-dependently. Protriptyline induced influx of Mn2+, indirectly implicating Ca2+ influx. Protriptyline-evoked Ca2+ entry was inhibited by nifedipine by 20% but was not altered by econazole, SKF96365, GF109203X, and phorbol-12-myristate-13-acetate (PMA). In Ca2+-free medium, treatment with protriptyline inhibited the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin-evoked [Ca2+]i rises. Conversely, treatment with thapsigargin inhibited 45% of protriptyline-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 failed to alter protriptyline-evoked [Ca2+]i rises. Protriptyline at 50-250 µM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in MG63 cells, protriptyline induced [Ca2+]i rises by evoking Ca2+ release from the endoplasmic reticulum and other stores in a PLC-independent manner, and Ca2+ entry via a nifedipine-sensitive Ca2+ pathway. Protriptyline also caused Ca2+-independent cell death.

The mechanism of protriptyline-induced Ca2+ movement and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.

Protriptyline, a tricyclic anti-depressant, is used primarily to treat the combination of symptoms of anxiety and depression. However, the effect of protriptyline on prostate caner is unknown. This study examined whether the anti-depressant protriptyline altered Ca(2+) movement and cell viability in PC3 human prostate cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)](i). Protriptyline evoked [Ca(2+)](i) rises concentration-dependently. The response was reduced by removing extracellular Ca(2+). Protriptyline-evoked Ca(2+) entry was inhibited by store-operated channel inhibitors (nifedipine, econazole and SKF96365), protein kinase C activator (phorbol 12-myristate 13 acetate, PMA) and protein kinase C inhibitor (GF109203X). Treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydr-oquinone (BHQ) in Ca(2+)-free medium inhibited 60% of protriptyline-evoked [Ca(2+)](i) rises. Conversely, treatment with protriptyline abolished BHQ-evoked [Ca(2+)](i) rises. Inhibition of phospholipase C with U73122 suppressed 50% of protriptyline-evoked [Ca(2+)](i) rises. At concentrations of 50-70 µM, protriptyline decreased cell viability in a concentration-dependent manner; which were not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, in PC3 cells, protriptyline evoked [Ca(2+)](i) rises by inducing phospholipase C-associated Ca(2+) release from the endoplasmic reticulum and other stores, and Ca(2+) influx via protein kinase C-sensitive store-operated Ca(2+) channels. Protriptyline caused cell death that was independent of [Ca(2+)](i) rises.

Effect of fluoxetine on [Ca²âº]i and cell viability in OC2 human oral cancer cells.

Fluoxetine is a serotonin-specific reuptake inhibitor that has been used as an antidepressant. This study examined the effect of fluoxetine on cytosolic free Ca²âº concentrations ([Ca2⁺]i) and viability in OC2 human oral cancer cells. The Ca²âº-sensitive fluorescent dye fura-2 was used to measure [Ca²âº]i, and the water soluble tetrazolium (WST-1) regent was used to measure viability. Fluoxetine induced [Ca²âº]i rises concentration-dependently. The response was reduced by half by removing extracellular Ca²âº. Fluoxetine-induced Ca²âº entry was enhanced by activation of protein kinase C (PKC) with phorbol 12-myristate 13 acetate (PMA) but was inhibited by inhibition of the enzyme with GF109203X. In Ca²âº-free medium, treatment with the endoplasmic reticulum Ca²âº pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) or thapsigargin abolished fluoxetine-evoked [Ca²âº]i rise. Conversely, treatment with fluoxetine inhibited BHQ/thapsigargin-evoked [Ca²âº]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished fluoxetine-induced [Ca²âº]i rise. At 20-80 µM, fluoxetine decreased cell viability concentration-dependently, which was not altered by chelating cytosolic Ca²âº with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). At 20-60 µM, fluoxetine induced apoptosis as detected by annexin V/propidium iodide (PI) staining. Together, in OC2 cells, fluoxetine induced [Ca²âº]i rises by evoking PLC-dependent Ca²âº release from the endoplasmic reticulum and Ca²âº entry via PKC-regulated mechanisms. Fluoxetine also caused Ca²âº-independent apoptosis.

Rise of [Ca²âº]i and apoptosis induced by M-3M3FBS in SCM1 human gastric cancer cells.

M-3M3FBS (2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide is a presumed phospholipase C activator which induced Ca²âº movement and apoptosis in different cell models. How- ever, the effect of m-3M3FBS on cytosolic free Ca²âº concentrations ([Ca²âº]i) and apoptosis in SCM1 human gastric cancer cells is unclear. This study explored whether m-3M3FBS elevated basal [Ca²âº]i levels in suspended cells by using fura-2 as a Ca²âº-sensitive fluorescent dye. M-3M3FBS at concentrations between 5-50 µM increased [Ca²âº]i in a concentration-dependent manner. The Ca²âº signal was reduced by half by removing extracellular Ca²âº. M-3M3FBS-induced Ca²âº influx was inhibited by nifedipine, econazole, SK&F96365, aristolochic acid, and GF109203X. In Ca²âº-free medium, 50 µM m-3M3FBS pretreatment inhibited the [Ca²âº]i rise induced by the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin partly reduced m-3M3FBS-induced [Ca²âº]i rise. Suppression of inositol 1,4,5-trisphosphate production with U73122 did not change m-3M3FBS- induced [Ca²âº]i rise. At concentrations between 25 and 50 µM m-3M3FBS killed cells in a concentration- dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca²âº with acetoxy-methyl ester of bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM). Annexin V/propidium iodide staining data suggest that m-3M3FBS induced apoptosis at 25 and 50 µM. M-3M3FBS also increased levels of superoxide. Together, in human gastric cancer cells, m-3M3FBS induced a [Ca²âº]i rise by inducing phospholipase C-independent Ca²âº release from the endoplasmic reticulum and Ca²âº entry via protein kinase C-sensitive store-operated Ca²âº channels. M-3M3FBS induced cell death that might involve apoptosis via reactive oxygen species production.

Predischarge oxygen uptake efficiency slope has short and long-term value in the prognosis of patients after acute myocardial infarction.

BACKGROUND: Patients who survive an acute myocardial infarction (AMI) have a higher risk of having a major cardiovascular event (MACE). Cardiopulmonary exercise testing (CPET) could develop prognostic stratification and prescribing exercise prescription. Patients after AMI frequently terminate CPET early with submaximal testing results. We aimed to look at the characteristics of patients' predischarge CPET variables after AMI intervention and find potential CPET variables with prognostic value. METHODS: Between July 2012 and August 2017, we recruited patients who survived first AMI after primary percutaneous coronary intervention and received predischarge CPET retrospectively in a tertiary medical center of Taiwan. Patients were followed-up on a MACE or administrative censoring occurred (up to 5 years). To identify significant predictors of a MACE, a Cox regression model was used. RESULTS: One hundred thirteen patients (103 men and 10 women) were studied, with an average age of 58.32 ± 12.49. MACE over 3 months, 2-years, and 5-years was 17.70%, 53.10%, and 62.83%, respectively. The oxygen uptake efficiency slope during the whole during of CPET (OUES 100) divided by body surface area (OUES 100/BSA) was found to be a significant event predictor for MACE at 3-month, 2- and 5-years. Cox regression analysis revealed that those with OUES 100/BSA <0.722 ( p = 0.004), OUES 100/BSA <0.859 ( p = 0.002), and OUES 100/BSA <0.829 ( p = 0.002) had a 7.14-fold, 3.47-fold, and 2.72-fold increased risk of 3-month, 2-year, and 5-year MACE, respectively. CONCLUSION: It is critical to identify a submaximal predictor during CPET for patients who survive AMI. Our findings suggested that OUES could be a significant prognostic indicator in patients after first AMI in both the short and long term.

Cardiopulmonary functional capacity in Taiwanese children with atrial septal defects.

BACKGROUND: Most existing studies measure atrial septal defect (ASD) outcomes based on morbidity rates such as atrial arrhythmias and heart failure rather than the functional assessment of physical capacity postprocedure. Few studies have evaluated cardiopulmonary function in ASD children. This study represents the largest sample population in the current research, encompassing a total of 122 Taiwanese children with ASD who had undergone treatment, to evaluate cardiopulmonary functional capacity through the implementation of cardiopulmonary exercise testing (CPET), and to investigate whether variations in treatment may impact their cardiopulmonary function. METHODS: This is a retrospective cohort study with the data collected from January 2010 to December 2021. All patients and controls (age-, sex-, and body mass index-matched) underwent CPET and pulmonary function testing. RESULTS: In total, 122 ASD patients (surgically closed ASDs 27, transcatheter-closed ASDs 48, and follow-up unrepaired ASD 47) and 244 healthy controls were recruited. The ASD group exhibited lower peak metabolic equivalent (MET), peak oxygen consumption (VO 2 , p < 0.001), and peak minute ventilation ( p = 0.028) along with MET and VO 2 at the anaerobic threshold (AT) ( p = 0.012) compared to the control group. No statistically significant differences were observed in the pulmonary function test. Among surgically closed, transcatheter closed and unrepaired ASD subgroups, no significant variances were seen in CPET and pulmonary function tests. CONCLUSION: Taiwanese ASD children exhibited diminished exercise capacity and cardiopulmonary performance compared to their healthy counterparts. Differences among specific ASD treatments in cardiopulmonary tests were non-significant.

Effect of sertraline on [Ca2+](i) and viability of human MG63 osteosarcoma cells.

The antidepressant, sertraline, has been shown to have diverse in vitro effects. This study examined whether sertraline altered [Ca(2+)](i) in MG63 human osteosarcoma cells by using fura-2 as a Ca(2+)-sensitive fluorescent dye. At 50-200 µM, sertraline induced a [Ca(2+)](i) rise in a concentration-dependent manner. Ca(2+) response was decreased by removing extracellular Ca(2+), suggesting that Ca(2+) entry and release contributed to the [Ca(2+)](i) signal. Sertraline-induced Ca(2+) entry was inhibited by nifedipine, La(3+), Gd(3+), and SK&F96365. When extracellular Ca(2+) was removed, pretreatment with the endoplasmic reticulum (ER) Ca(2+) pump inhibitor, thapsigargin, or 2,5-di-tert-butylhydroquinone (BHQ) abolished the sertraline-evoked [Ca(2+)](i) rise. Incubation with sertraline also abolished the thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C (PLC) with U73122 abolished the sertraline-induced [Ca(2+)](i) rise. At 20-30 µM, overnight treatment with sertraline killed cells in a concentration-dependent manner. The cytotoxic effect of sertraline was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data demonstrate that sertraline (30 µM) evoked apoptosis. Sertraline (20 and 30 µM) also increased levels of reactive oxygen species. Together, in human osteosarcoma cells, sertraline evoked a [Ca(2+)](i) rise by inducing PLC-dependent Ca(2+) release from the ER and Ca(2+) entry by L-type Ca(2+) channels and store-operated Ca(2+) channels. Sertraline induced cell death that may involve apoptosis by mitochondrial pathways.

Lower exercise capacity in children with asymptomatic atrial septal defect associated with circulatory impairment.

The exercise capacity and limitation in children with asymptomatic atrial septal defect (ASD) have not been explored thoroughly. The aim of our study was to examine the influence of asymptomatic ASD on exercise capacity in children. Fifty children with asymptomatic ASD who had undergone medical interventions at least 4 years ago and fifty normal children were recruited in this study. The exercise capacity was assessed by the symptom-limited exercise test through the Bruce treadmill protocol. The pulmonary function was also evaluated by the spirometry. Circulatory and ventilatory impairments were respectively reflected by chronotropic incompetence (CI) and ventilatory limitation as measured by the exercise test and spirometry. Eleven (22%) of children with ASD failed to reach the age-predicted peak heart rate during the exercise test. Also, children with ASD had significantly lower oxygen consumption at anaerobic threshold and peak exercise (P < 0.01). The rate of circulatory impairment was significantly higher in children with ASD (P < 0.01). However, the pulmonary function and ventilatory limitation were comparable between these two groups. Within the ASD group, children with CI had significantly worse peak oxygen consumption than their peers without CI (P < 0.01). Our study examined a larger population sample and confirmed that children with asymptomatic ASD, who had previously undergone medical interventions, had significantly worse exercise capacity than normal children. This difference in exercise capacity was mainly related to circulatory impairment. Our findings support the concerns of exercise limitation in ASD children.

M-3M3FBS-induced Ca² ⁺ movement and apoptosis in HA59T human hepatoma cells.

The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca² ⁺ concentrations ([Ca² ⁺ ]i ) in HA59T human hepatoma cells is unclear. This study explored whether m-3M3FBS elevated basal [Ca² ⁺ ]i levels in suspended cells by using fura-2 as a Ca² ⁺ -sensitive fluorescent dye. M-3M3FBS at concentrations of 10- 50 µM increased [Ca² ⁺ ]i in a concentration-dependent fashion. The Ca² ⁺ signal was reduced partly by removing extracellular Ca² ⁺ . M-3M3FBS-induced Ca² ⁺ influx was inhibited by nifedipine, econazole, SK&F96365, aristolochic acid, and GF109203X. In Ca² ⁺ -free medium, 50 µM m-3M3FBS pretreatment inhibited the [Ca² ⁺ ]i rise induced by the endoplasmic reticulum Ca² ⁺ pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin partly reduced m-3M3FBS-induced [Ca² ⁺ ]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 did not alter m-3M3FBS-induced [Ca² ⁺ ]i rise. At concentrations between 10 and 40 µM m-3M3FBS killed cells in a concentration-dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca² ⁺ with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data suggest that m-3M3FBS induced apoptosis in a concentration-dependent manner. M-3M3FBS also increased levels of reactive oxygen species. Together, in human hepatoma cells, m-3M3FBS induced a [Ca² ⁺ ]i rise by inducing phospholipase C-independent Ca² ⁺ release from the endoplasmic reticulum and Ca² ⁺ entry via protein kinase C-sensitive store-operated Ca² ⁺ channels. M-3M3FBS induced cell death that might involve apoptosis via mitochondrial pathways.

Chronic Kidney Disease, But Not Diabetes, Can Predict 30-Day Outcomes in Patients with ST-Elevation Myocardial Infarction after Primary Percutaneous Coronary Intervention: A Single-Center Experience.

BACKGROUND: Patients with acute coronary syndrome and impaired renal function have been shown to have high mortality. However, there is scarce literature to date addressing the impact of diabetes mellitus (DM) and renal function on clinical outcomes of ST elevation myocardial infarction (STEMI) in Taiwan. METHOD: This study enrolled 512 STEMI patients who received primary percutaneous coronary intervention. Patients were divided into 4 groups including group 1: patients without DM or CKD (nDM-nCKD); group 2: patients with DM but without CKD (DM-nCKD); group 3: patients with CKD but without DM (nDM-CKD); group 4: patients with DM and CKD (DM-CKD). Patients were also classified into four groups based on their estimated glomerular filtration rates (eGFR): stage 1 (eGFR ≥ 90 ml/min/1.73 m(2), n = 163), stage 2 (eGFR = 89-60 ml/min/1.73 m(2), n = 171), stage 3 (eGFR = 59-30 ml/min/1.73 m(2), n = 136), and stage 4 (eGFR < 30 ml/min/1.73 m(2), n = 42). The complication rates, length of hospital stay, and 30-day outcomes were analyzed. RESULTS: The patients in both the nDM-CKD group and DM-CKD group had higher incidences of hypotension, intra-aortic balloon counterpulsation use, and respiratory failure (p < 0.005). They had significantly longer hospital stay and 30-day mortality rates (p < 0.001). The patients with CKD stage 3 and 4 had longer hospital stay and higher 30-day mortality rates (p < 0.001). However, DM was not an independent factor on the length of hospital stay and 30-day mortality rates. CONCLUSIONS: STEMI patients with impaired renal function, but not DM, had significantly longer hospital stay and higher 30-day mortality rates. KEY WORDS: Chronic kidney disease; Diabetes mellitus; Mortality; Primary percutaneous coronary intervention; ST-segment elevation myocardial infarction.

The Effect of Intensified Low Density Lipoprotein Cholesterol Reduction on Recurrent Myocardial Infarction and Cardiovascular Mortality.

BACKGROUND: Lipid-lowering therapy plays an important role in preventing the recurrence of cardiovascular events in patients after acute myocardial infarction (AMI). This study aimed to assess the effect of intensified low density lipoprotein cholesterol (LDL-C) reduction on recurrent myocardial infarction and cardiovascular mortality in patients after AMI. METHOD: The 562 enrolled AMI patients (84.2% male) were divided into two groups according to 3-month LDL-C decrease percentage equal to or more than 40% (n = 165) and less than 40% (n = 397). To evaluate the long-term efficacy of LDL-C reduction, the 5-year outcomes were collected, including time to the first occurrence of myocardial infarction and time to cardiovascular death. RESULTS: The baseline characteristics and complication rates were not different between the two study groups. The patients with 3-month LDL-C decrease ≥ 40% had higher baseline LDL-C and lower 3-month, 1-year, 2-year, 3-year, 4-year and 5-year LDL-C than the patients with 3-month LDL-C decrease < 40%. In Kaplan-Meier analyses, those patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction (p = 0.006) and survival rate (p = 0.02) at 5-year follow-up. The 3-month LDL-C < 40% parameter was significantly related to cardiovascular death (HR: 9.62, 95% CI 1.18-78.62, p < 0.04). CONCLUSIONS: After acute myocardial infarction, 3-month LDL-C decrease < 40% was identified to be a significant risk factor for predicting 5-year cardiovascular death. The patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction and lower cardiovascular mortality, even though these patients had higher baseline LDL-C value. KEY WORDS: Acute myocardial infarction; Cardiovascular death; Low-density lipoprotein cholesterol; Mortality; Statin.