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The brachiocephalic vein (BCV), also known as the innominate vein, is a central vein in the upper chest formed by merging the internal jugular and subclavian veins. It plays a crucial role in venous return from the head, neck, and upper extremities and is significant in procedures such as pacemaker and implantable cardioverter-defibrillator (ICD) placement, chemotherapy ports, and central venous catheter insertions. The presence of foreign bodies and local malignancy are major risk factors for thrombosis in the BCV. As part of the deep venous system, BCV thrombosis (BCVT) is a rare condition but can lead to serious complications like superior vena cava syndrome and, rarely, pulmonary embolism. This case report presents an 82-year-old woman with a history of heart failure with reduced ejection fraction, coronary artery disease, atrial fibrillation, HIV, pulmonary embolism, systemic lupus erythematosus, and breast cancer who required an ICD placement due to persistent systolic dysfunction. During the procedure, chronic BCVT leading to the stenosis was incidentally discovered, necessitating urgent vascular intervention to establish venous patency. The patient's complex medical history, including previous chemotherapy through a central venous catheter, contributed to the risk factors for BCVT. The multidisciplinary approach led to successful ICD placement and the reinstatement of anticoagulation therapy. This case underscores the rarity and severity of BCVT and highlights the importance of pre-procedural imaging, such as CT venography, in patients with multiple risk factors. Additionally, the report suggests considering leadless ICD technology for patients with limited venous access to avoid complications. The findings emphasize the critical need for thorough evaluation and planning in complex cases to ensure successful outcomes.
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Background: The risk and metabolic effects of obesity are determined by the distribution of fat throughout the body. It has been proposed that the distribution of abdominal fat is more closely related to the metabolic risks of obesity. High prevalence of overweight and obesity has thereby contributed to an increased uptake of surgical subcutaneous fat removal (SSFR) procedures. The goal of this study was to determine whether bioelectrical impedance analysis (Tanita system) can be used to detect the removal of excess abdominal subcutaneous fat tissue during SSFR when studying the metabolic effects of such procedures. Methods: Study population comprised patients who received body contouring procedures at the Hamad General Hospital's plastic surgery department between November 2020 and December 2022. To evaluate the factors of interest, subjects were prospectively followed up at two time points: within 1 week before the surgery and within 1-2 weeks thereafter. The following factors were measured: body weight, body fat percentage, body fat mass, body mass index (BMI), fat-free mass, estimated muscle mass, total body water, visceral fat score, and basal metabolic rate. Results: In total, 22 patients were included in the study. The two visits' medians for height, weight, BMI, fat percent (fat%), fat mass, visceral fat rating, and Doi's weighted average glucose (dwAG) were compared. Only in the case of Tanita fat% and fat mass, were the preoperative and postoperative medians significantly different. Furthermore, there was no association between these Tanita measures and dwAG or homeostatic model assessment (HOMA; insulin resistance [IR]) changes (before and after surgery). Tanita measures overestimated fat loss, as seen by the mountain plot and Bland-Altman plot agreement methods. Conclusions: Our findings indicated that the only two Tanita measures exhibited meaningful early associations with the amount of tissue excised which were fat mass and fat% differences. Although dwAG and HOMA-IR are not impacted immediately postsurgery, a trend was seen that suggested improvements in those parameters, even though the changes are not clinically significant.
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Impedância Elétrica , Gordura Subcutânea , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Contorno Corporal/efeitos adversos , Estudos Prospectivos , Índice de Massa Corporal , Composição Corporal , Obesidade/cirurgia , Obesidade/diagnósticoRESUMO
Over the years, several international guidelines have been developed by specialist organizations for the diagnosis of gestational diabetes mellitus (GDM). However, these guidelines vary and lack consensus on what level of glycemia defines GDM and worryingly, there is now evidence of over- or- under-diagnosis of women with GDM by current criteria. Towards this end, the National Priorities Research Program (NPRP) funded a program of research aimed at elucidating the problem with GDM diagnosis. It was determined, on completion of the project, that the solution required diagnosis of graded levels of dysglycemia in pregnancy and not just a diagnosis of presence or absence of GDM. A new diagnostic criterion (called the NPRP criterion) was created based on a single numerical summary of the three readings from the oral glucose tolerance test (GTT) that diagnosed women in pregnancy into four levels: normal, impaired, GDM and high risk GDM. This paper now examines existing GDM criteria vis-à-vis the NPRP criterion. It is noted that no significant change has happened over the years for existing criteria except for a gradual reduction in the threshold values of individual time-points or the number of time points, bringing us towards over-diagnosis of GDM in pregnancy. The new criterion unifies all readings from the GTT into one numerical value and, because it results in four levels of glycemia, represents a new way forwards for GDM diagnosis and can potentially reduce the rates of under diagnosis and over diagnosis of GDM.
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Diabetes Gestacional , Teste de Tolerância a Glucose , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/sangue , Humanos , Feminino , Gravidez , Glicemia/metabolismo , Glicemia/análise , Guias de Prática Clínica como AssuntoRESUMO
Introduction The most significant element in halting the coronavirus disease 2019 (COVID-19) epidemic was the availability of reliable and efficient vaccines. Vaccine acceptability is influenced by many factors, including perceptions of the vaccine's safety and side effects. Adverse reactions to vaccines can vary with regard to the type, although they are frequently mild, localized, temporary, and self-limiting. Therefore, this study aimed to assess the prevalence of side effects experienced by postmenopausal women after receiving the Sinovac vaccine. Methods This multicenter, prospective cross-sectional study was carried out at multiple centers in Karachi, Pakistan. In this study, the non-probability sampling method was used. The study continued from August 1, 2022, to January 31, 2023, for six months. The study comprised 600 postmenopausal women over the age of 50 years who received two doses of Sinovac COVID-19 vaccination. Demographic parameters such as gender, the existence of comorbidities, and local and systemic side effects in postmenopausal women were documented as frequencies and percentages. Age, weight, and duration of comorbidities are expressed as means and standard deviations. Results The study findings showed that the mean age of study participants was 63.93 ± 8.24 years. There were related comorbidities with hypertension and diabetes mellitus in 181 (30.2%) and 40 (6.7%) women, respectively. Fever was the most often reported side effect, with 349 (58.2%) participants reporting it and 198 (56.7%) participants reporting it as mild. After the second dose, 234 (39.5%) participants reported fever as their most frequent adverse effect, and 158 (67.5%) of them reported it was mild. Conclusion This study concluded that the most commonly reported side effects among postmenopausal women were fever, pain, and swelling at the injection site after getting either dose of Sinovac vaccine. These overall side effects were generally mild to moderate in intensity, not life-threatening, and did not require hospitalization, although fever was reported in severe intensity in some cases, particularly after the first dose.
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Introduction: Randomized controlled trials (RCTs) are the gold standard to evaluate the efficacy of interventions (e.g., drugs and vaccines), yet the sample size of RCTs is often limited for safety assessment. Non-randomized studies of interventions (NRSIs) had been proposed as an important alternative source for safety assessment. In this study, we aimed to investigate whether there is any difference between RCTs and NRSIs in the evaluation of adverse events. Methods: We used the dataset of systematic reviews with at least one meta-analysis including both RCTs and NRSIs and collected the 2 × 2 table information (i.e., numbers of cases and sample sizes in intervention and control groups) of each study in the meta-analysis. We matched RCTs and NRSIs by their sample sizes (ratio: 0.85/1 to 1/0.85) within a meta-analysis. We estimated the ratio of the odds ratios (RORs) of an NRSI against an RCT in each pair and used the inverse variance as the weight to combine the natural logarithm of ROR (lnROR). Results: We included systematic reviews with 178 meta analyses, from which we confirmed 119 pairs of RCTs and NRSIs. The pooled ROR of NRSIs compared to that of RCTs was estimated to be 0.96 (95% confidence interval: 0.87 and 1.07). Similar results were obtained with different sample size subgroups and treatment subgroups. With the increase in sample size, the difference in ROR between RCTs and NRSIs decreased, although not significantly. Discussion: There was no substantial difference in the effects between RCTs and NRSIs in safety assessment when they have similar sample sizes. Evidence from NRSIs might be considered a supplement to RCTs for safety assessment.
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Rapid reviews have been widely employed to support timely decision-making, and limiting the search date is the most popular approach in published rapid reviews. We assessed the accuracy and workload of search date limits on the meta-analytical results to determine the best rapid strategy. The meta-analyses data were collected from the Cochrane Database of Systematic Reviews (CDSR). We emulated the rapid reviews by limiting the search date of the original CDSR to the recent 40, 35, 30, 25, 20, 15, 10, 7, 5, and 3 years, and their results were compared to the full meta-analyses. A random sample of 10% was drawn to repeat the literature search by the same timeframe limits to measure the relative workload reduction (RWR). The relationship between accuracy and RWR was established. We identified 21,363 meta-analyses of binary outcomes and 7683 meta-analyses of continuous outcomes from 2693 CDSRs. Our results suggested that under a maximum tolerance of 5% and 10% on the bias of magnitude, a limit on the recent 20 years can achieve good accuracy and at the same time save the most workload. Under the tolerance of 15% and 20% on the bias, a limit on the recent 10 years and 15 years could be considered. Limiting the search date is a valid rapid method to produce credible evidence for timely decisions. When conducting rapid reviews, researchers should consider both the accuracy and workload to make an appropriate decision.
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Publicações , Projetos de Pesquisa , Testes Diagnósticos de Rotina , Estudos Epidemiológicos , Revisões Sistemáticas como AssuntoRESUMO
AIMS: Attributes that operationally conceptualize diabetes self-management education (DSME) interventions have never been studied previously to assess their impact on relevant outcomes of interest in people with type 2 diabetes (T2D). The aim of this study was to determine the impact of existing interventions classified by their delivery of skills or information related attributes on immediate (knowledge), intermediate (physical activity), post-intermediate (HbA1c), and long-term (quality of life) outcomes in people with T2D. METHODS: PubMed, Embase, PsycINFO, and Cochrane Library/Cochrane CENTRAL as well as the grey literature were searched to identify interventional studies that examined the impact of DSME interventions on the four different outcomes. Eligible studies were selected and appraised independently by two reviewers. A meta-regression analysis was performed to determine the impact of delivery of the skills- and information-related attributes on the chosen outcomes. RESULTS: 142 studies (n = 25,511 participants) provided data, of which 39 studies (n = 5278) reported on knowledge, 39 studies (n = 8323) on physical activity, 99 studies (n = 17,178) on HbA1c and 24 studies (n = 5147) on quality of life outcomes. Meta-regression analyses demonstrated that skills-related attributes had an estimated effect suggesting improvement in knowledge (SMD [standardized mean difference] increase of 0.80; P = 0.025) and that information-related attributes had an estimated effect suggesting improvement in quality of life (SMD increase of 0.96; P = 0.405). Skill- and information-related attributes did not have an estimated effect suggesting improvement in physical activity or in HbA1c. CONCLUSIONS: The study findings demonstrate that the skills and information related attributes contribute to different outcomes for people with T2D. This study provides, for the first time, preliminary evidence for differential association of the individual DSME attributes with different levels of outcome.
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Diabetes Mellitus Tipo 2 , Autogestão , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Exercício Físico , Humanos , Qualidade de Vida , Análise de RegressãoRESUMO
AIMS: With the rising number of outcomes being reported following gestational diabetes (GDM), the outcomes in existing studies vary widely making it challenging to compare and contrast the effectiveness of different interventions for GDM. The purpose of this study was to develop a core outcome and measurement set (COS) for GDM treatment trials. MATERIALS & METHODS: A Delphi study with structured consultation with stakeholders and discussion within a specialist Gestational Metabolic Group (GEM) were combined with a comprehensive systematic search across different databases (PubMed, Cochrane Library, and Embase). Several Delphi rounds over 2 years were conducted culminating in this report. RESULTS: The process resulted in a targeted set of outcomes constituting a "GEM treatment set" aligned with expert opinion. The final COS also included a measurement set for the 11 important clinical outcomes from three major domains: maternal metabolic, fetal, and pregnancy related. CONCLUSIONS: Based on the results of this study, it is recommended that future clinical trials on GDM report outcomes uniformly keeping to the recommended COS outcomes.
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CONTEXT: The comparative efficacy of gestational diabetes (GDM) treatments lack conclusive evidence for choice of first-line treatment. OBJECTIVES: The aim of this study was to compare the efficacy of metformin and glibenclamide to insulin using a core outcome set (COS) to unify outcomes across trials investigating the treatment of gestational diabetes mellitus. STUDY DESIGN: A network meta-analysis (NMA) was conducted. DATA-SOURCE: PubMed, Embase, and Cochrane Controlled Register of Trials were searched from inception to January 2020. STUDY SELECTION: RCTs that enrolled pregnant women who were diagnosed with GDM and that compared the efficacy of different pharmacological interventions for the treatment of GDM were included. META-ANALYSIS: A generalized pairwise modelling framework was employed. RESULTS: A total of 38 RCTs with 6046 participants were included in the network meta-analysis. Compared to insulin, the estimated effect of metformin indicated improvements for weight gain (WMD -2·39 kg; 95% CI -3·31 to -1·46), maternal hypoglycemia (OR 0.34; 95% CI 0.12 to 0·97) and LGA (OR 0.61; 95% CI 0.38 to 0·98). There were also improvements in estimated effects for neonatal hypoglycemia (OR 0.48; 95% CI 0.19 to 1·25), pregnancy induced hypertension (OR 0.63; 95% CI 0.37 to 1·06), and preeclampsia (OR 0.74; 95% CI 0.538 to 1·04), though with limited evidence against our model hypothesis of equivalence with insulin for these outcomes. CONCLUSION: Metformin is, at least, comparable to insulin for the treatment of GDM. Glibenclamide appears less favorable, in comparison to insulin, than metformin.
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Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Feminino , Glibureto/uso terapêutico , Humanos , Gravidez , Resultado do TratamentoRESUMO
BACKGROUND: This report and literature review describes a case of a COVID-19 patient who suffered a cerebellar stroke requiring neurosurgical decompression. This is the first reported case of a sub-occipital craniectomy with brain biopsy in a COVID-19 patient showing leptomeningeal venous intimal inflammation. CLINICAL DESCRIPTION: The patient is a 48-year-old SARS-COV-2 positive male with multiple comorbidities, who presented with fevers and respiratory symptoms, and imaging consistent with multifocal pneumonia. On day 5 of admission, the patient had sudden change in mental status, increased C-Reactive Protein, ferritin and elevated Interleukin-6 levels. Head CT showed cerebral infarction from vertebral artery occlusion. Given subsequent rapid neurologic decline from cerebellar swelling and mass effect on his brainstem emergent neurosurgical intervention was performed. Brain biopsy found a vein with small organizing thrombus adjacent to focally proliferative intima with focal intimal neutrophils. CONCLUSION: A young man with COVID-19 and suspected immune dysregulation, complicated by a large cerebrovascular ischemic stroke secondary to vertebral artery thrombosis requiring emergent neurosurgical intervention for decompression with improved neurological outcomes. Brain biopsy was suggestive of inflammation from thrombosed vessel, and neutrophilic infiltration of cerebellar tissue.
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Giant aneurysms of the left main coronary artery are one of the rarest findings in cardiology, encountered in less than 0.02% of patients. The presentation is usually the same as coronary artery disease since most coronary aneurysms in the western world are associated with atherosclerosis. Here we report the first case of giant aneurysm of the left main coronary artery presenting as ventricular tachycardia with multiple shocks of the defibrillator in a 57-year-old man with heart failure. We also review the etiology, pathology, and management of coronary aneurysms.
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Cardiac arrhythmias have been reported in the setting of coronavirus disease 2019 (COVID-19) infection. To date various tachyarrhythmias have been noted. This case report describes an atypical clinical hospitalization course of high-degree atrioventricular (AV) block in the setting of COVID-19 infection which required no intervention. This case highlights the importance of an initial electrocardiogram (ECG) upon presentation and consideration for constant cardiac monitoring in select patients.
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BACKGROUND: In January 2015, the Centers for Disease Control and Prevention (CDC)/National Health Safety Network (NHSN) changed the definition of catheter-associated urinary tract infection (CAUTI). We evaluated the outcomes of a robust CAUTI prevention program when we performed surveillance using the old definition (before 2015) versus the new definition (after 2015). This is the first study to evaluate how the change in CDC/NHSN definitions affected the outcomes of a CAUTI reduction program. METHODS: Baseline was from January 2012 to September 2014; the intervention period was from October 2014 to February 2016. Staff nurses were trained to be liaisons of infection prevention (Link Nurses) with clearly defined CAUTI prevention goals and with ongoing monthly activities. CAUTI incidence per 1000 catheter days was compared between the baseline and intervention periods, using the 2 definitions. RESULTS: With the new definition, CAUTIs decreased by 33%, from 2.69 to 1.81 cases per 1000 catheter days (incidence rate ratio [IRR] = 0.67; 95% confidence interval [CI]: 0.48-0.93; P < .016). With the old definition, CAUTIs increased by 12%, from 3.38 to 3.80 cases per 1000 catheter days (IRR = 1.12; 95% CI: 0.88-1.43; P = .348). CONCLUSION: We aggressively targeted CAUTI prevention, but a reduction was observed only with the new definition. Our findings stress the importance of having a reasonably accurate surveillance definition to monitor infection prevention initiatives.
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Infecções Relacionadas a Cateter/prevenção & controle , Infecções Urinárias/prevenção & controle , Infecções Relacionadas a Cateter/diagnóstico , Humanos , Papel do Profissional de Enfermagem , Berçários Hospitalares , Terminologia como Assunto , Atenção Terciária à Saúde , Cateteres Urinários/efeitos adversos , Infecções Urinárias/diagnósticoRESUMO
Tetralogy of Fallot (TOF) is a cyanotic congenital heart disease which, without corrective surgery, has a poor prognosis. These patients have an increased incidence of arrhythmias both supraventricular and ventricular post surgical correction. The supraventricular arrhythmias are usually related to the scar tissue at the surgical repair site. We present a case of a young male patient status post TOF repair who presented with a supraventricular tachycardia which was found to be unrelated to his surgical scar.
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Malposition of the right ventricular lead into the left ventricle is an unusual complication of challenging management. We report a case of an elderly woman with a dual chamber permanent pacemaker implanted 2 months before admission because of high grade AV block, who presented to our institution with sub acute subdural hematoma along the left fronto-parietal area. Incidental ventricular pacemaker lead in the left ventricle was found on chest CT scan. The patient was not candidate for anticoagulation due to her recent subdural hematoma, hence a discussion about the risks of explantation of the pacemaker lead led to patient's lead extraction without any complication.
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The clinical findings of Takatsubo Cardiomyopathy and acute myocardial infarction can be very similar. While Takatsubo cardiomyopathy rarely leads to severe complications, acute myocardial infarction can be life threatening. Treatment of both these conditions is different and so it is imperative for clinicians to have a high index of suspicion for either. Several EKG differences between the two entities have been proposed. This article summarizes the EKG changes most likely seen in Takatsubo cardiomyopathy and compares them to those seen in Acute Myocardial infarction.
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BACKGROUND: Lubiprostone, used clinically (b.i.d.) to treat constipation, has been reported to increase transepithelial Cl(-) transport in T84 cells by activating ClC-2 channels. AIM: To identify the underlying signaling pathway, we explored the effects of short-term and overnight lubiprostone treatment on second messenger signaling and Cl(-) transport. METHODS: Cl(-) transport was assessed either as I(sc) across T84 monolayers grown on Transwells and mounted in Ussing chambers or by the iodide efflux assay. [cAMP](i) was measured by enzyme immunoassay, and [Ca(2+)](i) by Fluo-3 fluorescence. Quantitation of apical cell surface CFTR protein levels was assessed by Western blotting and biotinylation with the EZ-Link Sulfo-NHS-LC-LC-Biotin. ClC-2 mRNA level was studied by RT-PCR. RESULTS: Lubiprostone and the cAMP stimulator, forskolin, caused comparable and maximal increases of I(sc) in T84 cells. The I(sc) effects of lubiprostone and forskolin were each suppressed if the tissue had previously been treated with the other agent. These responses were unaltered even if the monolayers were treated with lubiprostone overnight. Lubiprostone-induced increases in iodide efflux were ~80% of those obtained with forskolin. Lubiprostone increased [cAMP](i). H89, bumetanide, or CFTR(inh)-172 greatly attenuated lubiprostone-stimulated Cl(-) secretion, whereas the ClC-2 inhibitor CdCl(2) did not. Compared to controls, FSK-treatment increased membrane-associated CFTR by 1.9 fold, and lubiprostone caused a 2.6-fold increase in apical membrane CFTR as seen by immunoblotting following cell surface biotinylation. CONCLUSIONS: Lubiprostone activates Cl(-) secretion in T84 cells via cAMP, protein kinase A, and by increasing apical membrane CFTR protein.
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Alprostadil/análogos & derivados , Carcinoma/metabolismo , Cloretos/metabolismo , AMP Cíclico/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Alprostadil/farmacologia , Benzoatos/farmacologia , Transporte Biológico/efeitos dos fármacos , Bumetanida/farmacologia , Catárticos/farmacologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Colforsina/farmacologia , Neoplasias do Colo/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lubiprostona , Tiazolidinas/farmacologiaRESUMO
BACKGROUND: The correlation between spontaneous calcium oscillations (S-CaOs) and arrhythmogenesis has been investigated in a number of theoretical and experimental in vitro models. There is an obvious lack of studies that directly investigate how the kinetics of S-CaOs correlates with a specific arrhythmia in the in vivo heart. OBJECTIVES: The purpose of the study is to investigate the correlation between the kinetics of S-CaOs and arrhythmogenesis in the intact heart using an experimental model of ischemia/reperfusion (I/R). METHODS: Perfused Langendorff guinea pig (GP) hearts were subjected to global I/R (10-15 minutes/10-15 minutes). The heart was stained with a voltage-sensitive dye (RH237) and loaded with a Ca2+ indicator (Rhod-2 AM). Membrane voltage (Vm) and intracellular calcium transient (Ca(i)T) were simultaneously recorded with an optical mapping system of two 16 x 16 photodiode arrays. S-CaOs were considered to arise from a localized focal site within the mapped surface when these preceded the associated membrane depolarizations by 2-15 ms. RESULTS: In 135 episodes of ventricular arrhythmias from 28 different GP experiments, 23 were linked to S-CaOs that were considered to arise from or close to the mapped epicardial window. Self-limited or sustained S-CaOs had a cycle length of 130-430 ms and could trigger propagated ventricular depolarizations. Self-limited S-CaOs that followed the basic beat action potential (AP)/Ca(i)T closely resembled phase 3 early afterdepolarizations. Fast S-CaOs could remain confined to a localized site (concealed) or exhibit varying conduction patterns. This could manifest as (1) an isolated premature beat (PB), bigeminal, or trigeminal rhythm; (2) ventricular tachycardia (VT) when a regular 2:1 conduction from the focal site develops; or (3) ventricular fibrillation (VF) when a complex conduction pattern results in wave break and reentrant excitation. CONCLUSIONS: The study examined, for the first time in the intact heart, the correlation between the kinetics of focal S-CaOs during I/R and arrhythmogenesis. S-CaOs may remain concealed or manifest as PBs, VT, or VF. A "benign looking" PB during I/R may represent "the tip of the iceberg" of an underlying potentially serious arrhythmic mechanism.
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Arritmias Cardíacas/fisiopatologia , Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Eletrofisiologia , Cobaias , Sistema de Condução Cardíaco/fisiopatologia , Cinética , Masculino , Óptica e FotônicaRESUMO
Repolarization alternans has been considered a strong marker of electrical instability. The objective of this study was to investigate the hypothesis that ischemia-induced contrasting effects on the kinetics of membrane voltage and intracellular calcium transient (Ca(i)T) can explain the vulnerability of the ischemic heart to repolarization alternans. Ischemia-induced changes in action potential (AP) and Ca(i)T resulting in alternans were investigated in perfused Langendorff guinea pig hearts subjected to 10-15 min of global no-flow ischemia followed by 10-15 min of reperfusion. The heart was stained with 100 microl of rhod-2 AM and 25 microl of RH-237, and AP and Ca(i)T were simultaneously recorded with an optical mapping system of two 16 x 16 photodiode arrays. Ischemia was associated with shortening of AP duration (D) but delayed upstroke, broadening of peak, and slowed decay of Ca(i)T resulting in a significant increase of Ca(i)T-D. The changes in APD were spatially heterogeneous in contrast to a more spatially homogeneous lengthening of Ca(i)T-D. Ca(i)T alternans could be consistently induced with the introduction of a shorter cycle when the upstroke of the AP occurred before complete relaxation of the previous Ca(i)T and generated a reduced Ca(i)T. However, alternans of Ca(i)T was not necessarily associated with alternans of APD, and this was correlated with the degree of spatially heterogeneous shortening of APD. Sites with less shortening of APD developed alternans of both Ca(i)T and APD, whereas sites with greater shortening of APD could develop a similar degree of Ca(i)T alternans but slight or no APD alternans. This resulted in significant spatial dispersion of APD. The study shows that the contrasting effects of ischemia on the duration of AP and Ca(i)T and, in particular, on their spatial distribution explain the vulnerability of ischemic heart to alternans and the increased dispersion of repolarization during alternans.