Feasibility of Transatrial Access for Epicardial Ablation: Evaluation of 2 Different Techniques in Swine.

BACKGROUND: The subxiphoid pericardial access is technically difficult and has a considerable rate of complications, thus transatrial access may be an alternative. OBJECTIVES: This study sought to assess the feasibility and safety of this strategy regarding periprocedural period and after 1-week follow-up. METHODS: The investigators performed epicardial mapping through transatrial puncture in 20 swine. Animals were divided into group A, in which aspiration of the sheath was performed to maintain negative pressure after the withdraw of the catheters, and group B, in which a device (Konar-MF VSD Occluder) was delivered to occlude the right atrial appendage perforation. Bleeding was investigated immediately and 1 week after. RESULTS: Access was safe in 19 of 20 animals (95%) with small amount of bleeding (6.4 ± 6 mL). In group A (n = 10), 1 animal presented hemopericardium right after the puncture. In the other 9, epicardial ablation was performed and 60.0 ± 28.0 mL of blood was aspirated without events. After 1 week, fibrin-hemorrhagic pericarditis was identified in 3 animals. In group B (n = 10), reaching the epicardial surface was possible in all animals. An adequate position of the prosthesis was obtained in 90% (9 of 10). One death occurred in the immediate postoperative period, secondary to pneumothorax. After 1 week, postmortem analysis showed absence of pericardial bleeding and a normal-appearing pericardium in the 8 animals with adequate prosthesis position. CONCLUSIONS: Transatrial access allows epicardial mapping and ablation. Sheath removal after negative pressure contributes to achieving acute bleeding control but does not prevent its occurrence. The use of the device prevents bleeding and hemorrhagic pericarditis.

Transient ascending ST-segment depression and widening of the S wave in 3-channel Holter monitoring-A sign of dromotropic disturbance in the right ventricular outflow tract in the Brugada syndrome: A report of five cases.

BACKGROUND: Brugada syndrome (BrS) is somewhat a challenging diagnosis, due to its dynamic pattern. One of the aspects of this disease is a significant conduction disorder located in the right ventricular outflow tract (RVOT), which can be explained as a consequence of low expression of Connexin-43. This decreased conduction speed is responsible for the typical electrocardiographic pattern. Opposite leads located preferably in inferior leads of the electrocardiogram may show a deep and widened S wave associated with ascending ST segment depression. Holter monitoring electrocardiographic (ECG) aspects is still a new frontier of knowledge in BrS, especially in intermittent clinical presentations. METHODS: We describe, as an exploratory analysis, five case series of intermittent type 1 BrS to demonstrate the appearance of ascending ST segment depression and widening of the S wave, during 3-channel 24h-Holter monitoring (C1, C2 and C3) with bipolar leads. RESULTS: In the five cases described, the ST segment depression was observed mainly in C2, but in some cases also in C1 and C3. Only case 1 presented concomitant intermittent elevation of the ST segment in C1. All cases were intermittent. CONCLUSION: The recognition of an ECG pattern with ascending ST-segment depression and widening of the S wave in 3-channel Holter described in this case series should raise a suspicion of the BrS and suggests the counterpart of a dromotropic disturbance registered in the RVOT and/or reciprocal changes.

Low rate of life-threatening events and limitations in predicting invasive and noninvasive markers of symptoms in a cohort of type 1 Brugada syndrome patients: Data and insights from the GenBra registry.

BACKGROUND: Brugada syndrome (BrS) has diagnostic challenges and controversial risk assessment. We aimed to investigate invasive and noninvasive parameters in symptomatic and asymptomatic patients from a Brazilian cohort of type-1 BrS. METHODS: Patients with spontaneous and drug-induced type-1 BrS were classified into two groups, asymptomatic (n = 116, 84.1%) and symptomatic (n = 22, 15.9%; 13 with arrhythmogenic syncope, 9 with aborted sudden cardiac death). Genetic testing, EPS parameters, and electrocardiogram (ECG) parameters were analyzed. RESULTS: A total of 138 consecutive patients were eligible, 101 men (73.2%), mean 41.4 years, mostly probands (79%). Spontaneous pattern, observed in 77.5% of the patients, was associated with symptoms only if expressed in V1 and V2 standard position (not high precordial leads; p = .014). All symptomatic patients were probands. The presence of right ventricular outflow tract conduction delay (RVOTcd) signs, positive EPS, and SCN5A status was similar between symptomatic and asymptomatic subjects. During the mean 75-month follow-up, eight patients had appropriate therapies. All had spontaneous type-1 ECG pattern and 2/8 (25%) were asymptomatic, with positive EPS. The overall LAE incidence of 1.1% per year dropped to 0.27% in asymptomatic patients. RVOTcd occurred more frequently in SCN5A carriers (QRS-f 33.3% vs. 7.7%; p = .005, AVR sign 58.3% vs. 13.6%; p < .001; deep S in lead I 75% vs. 48.5%, p = .025%), as well as longer HV interval (66 vs. 49 ms; p < .001). CONCLUSIONS: Spontaneous type-1 Brugada pattern in standard leads and proband status were more frequent in symptomatic subjects. RVOTcd, more common in SCN5A carriers, did not predict symptoms in BrS patients. EPS exhibited limited prognostic value for this low-risk population.

2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: Executive summary.

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.

2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.

Prevenção da fibrilação atrial além do antiarrítmico - abordagem multifatorial / Atrial fibrillation prevention beyond antiarrhythmic drug therapy - multifactorial approach

A prevenção da fibrilação atrial (FA) envolve uma abordagem individualizada, multidisciplinar e integrada do paciente, que vai além da arritmia per se. Por se tratar de uma arritmia multifatorial e com fisiopatologia complexa, os pacientes com FA devem ser avaliados em sua integralidade, que inclui aspectos eletrocardiográficos, eletrofisiológicos, medidas comportamentais e otimização de tratamento de doenças crônicas, como hipertensão arterial e insuficiência cardíaca. Neste artigo descrevere-mos as principais intervenções estudadas na literatura com benefício na prevenção da fibrilação atrial

AF (atrial fibrillation) prevention involves an ndividualized, multidisciplinary and integrated approach taken by the patient, which emcompasses more than just arrhy- thmima per se. Because it is a multifactorial arrhythmia with complex physiopathology, patients with AF should undergo a complete assessment, including electrocardiographic and electrophysiological aspects, behavioral measures and optimization of the treatment of chronic diseases, such as hypertension and heart failure. In this article we describe the main interventions studied in literature that are beneficial in the prevention of atrial fibrillation

Differential diagnosis of wide QRS tachycardias: comparison of two electrocardiographic algorithms.

AIMS: This study's aim is to compare the ability of two ECG criteria to differentiate ventricular (VT) from supraventricular tachycardia (SVT): Brugada et al. [horizontal plane (HP) leads] and Vereckei et al. [frontal plane (FP), specifically aVR lead], having electrophysiological study (EPS) as gold standard. After comparing, suggestions for better diagnosis of wide QRS-complex tachycardia (WCT) in emergency situations were made. METHODS AND RESULTS: Fifty-one consecutive patients with 12-lead ECG registered during EPS-induced regular WCT were selected. Each ECG was split into two parts: HP (V1-V6) and FP (D1-D3, aVR, aVL, and aVF), randomly distributed to three observers, blinded for EPS diagnosis and complementary ECG plane, resulting in total 306 ECG analyses. Observers followed the four steps of both algorithms, counting time-to-diagnosis. Global sensitivity, specificity, percentage of incorrect diagnoses, and step-by-step positive/negative likelihood ratios (+LR and -LR) were calculated. Kaplan-Meier curve was plotted for final time-to-diagnosis. Inter-observer agreement was assessed with kappa-statistic. Global sensitivity was similarly high in FP and HP algorithms (89.2 vs. 90.1%), and incorrect classifications were 27.4 vs. 24.7%. Forty-eight correct analyses by Vereckei criteria took 9.13 s to diagnose VT in the first step, showing that first step was fast, with high +LR, generating nearly conclusive pre- (72.6%) to post-test (98.0%) changes for VT probability. CONCLUSION: Both algorithms as a whole are similar for diagnosis of WTC; however, the first step of Vereckei (initial R in aVR) is a simple, reproducible, accurate, and fast tool to use. The negativity of this step requires a 'holistic' approach to distinguish VT from SVT.

[The genera of Bethylidae (Hymenoptera: Chrysidoidea) in four areas of Atlantic Rain Forest from Espírito Santo, Brazil]. / Os gêneros de Bethylidae (Hymenoptera: Chrysidoidea) de quatro áreas de Mata Atlântica do Espírito Santo.

The generic richness and abundance of Bethylidae collected in four different hillside areas of Atlantic rain forest from Espírito Santo, Brazil were studied. The sites are Santa Maria de Jetibá (SMJ), Domingos Martins (DM), Pancas (P) and Atílio Vivacqua (AV). A total of 2,840 specimens of 12 genera were collected. Lepidosternopsis Ogloblin and Bakeriella Kieffer are first recorded from the State. Richness of taxa was calculated using first-order Jackknife richness with EstimateS program. Genera accumulation curves were ran to evaluate the samples. Abundance data were adjusted to the geometric distribution. Parameter k was used to compare areas. The generic profile was not equal for the sites we studied. The areas were considered disturbed. SMJ and DM presented genera richness bigger than in P and AV. The differences in the sites reflect the different preservation of each environment. Pseudisobrachium Kieffer and Dissomphalus Ashmead are most dominant genera in SMJ, DM and P, and Anisepyris Kieffer in AV. This study emphasizes the fact of Dissomphalus as the most abundant genus in rain forests. The generic profile found in AV is similar to that of some areas of Brazilian savannah.

Os gêneros de Bethylidae (Hymenoptera: Chrysidoidea) de quatro áreas de Mata Atlântica do Espírito Santo / The genera of Bethylidae (Hymenoptera: Chrysidoidea) in four areas of Atlantic Rain Forest from Espírito Santo, Brazil

Estudou-se a riqueza e abundância de gêneros de Bethylidae coletados em quatro áreas de mata de encosta da Mata Atlântica do Espírito Santo, com estados de preservação diferentes: Santa Maria de Jetibá (SMJ), Domingos Martins (DM), Pancas (P) e Atílio Vivácqua (AV). Foram coletados 2.840 espécimes alocados em 12 gêneros, sendo Lepidosternopsis Ogloblin e Bakeriella Kieffer citados pela primeira vez para esse estado. A riqueza dos táxons foi obtida através do procedimento Jackknife com auxílio do programa EstimateS. Curvas de acumulação de gêneros foram construídas para avaliar o esforço amostral. Os dados se ajustaram à distribuição geométrica e calculou-se o parâmetro k para comparar as localidades. O perfil genérico não foi equivalente em todas as localidades, e todas foram consideradas perturbadas. SMJ e DM apresentaram riqueza de gêneros maior em comparação com P e AV. As diferenças relatadas neste estudo para as áreas amostradas refletem o grau diferente de preservação das matas. Pseudisobrachium Kieffer e Dissomphalus Ashmead foram os gêneros mais abundantes em SMJ, DM e P e Anisepyris Kieffer em AV. Este estudo reforça o fato de Dissomphalus ser mais abundante em florestas tropicais úmidas e que o perfil genérico encontrado em AV assemelha-se a dados publicados para o cerrado.

The generic richness and abundance of Bethylidae collected in four different hillside areas of Atlantic rain forest from Espírito Santo, Brazil were studied. The sites are Santa Maria de Jetibá (SMJ), Domingos Martins (DM), Pancas (P) and Atílio Vivacqua (AV). A total of 2,840 specimens of 12 genera were collected. Lepidosternopsis Ogloblin and Bakeriella Kieffer are first recorded from the State. Richness of taxa was calculated using first-order Jackknife richness with EstimateS program. Genera accumulation curves were ran to evaluate the samples. Abundance data were adjusted to the geometric distribution. Parameter k was used to compare areas. The generic profile was not equal for the sites we studied. The areas were considered disturbed. SMJ and DM presented genera richness bigger than in P and AV. The differences in the sites reflect the different preservation of each environment. Pseudisobrachium Kieffer and Dissomphalus Ashmead are most dominant genera in SMJ, DM and P, and Anisepyris Kieffer in AV. This study emphasizes the fact of Dissomphalus as the most abundant genus in rain forests. The generic profile found in AV is similar to that of some areas of Brazilian savannah.

Radiofrequency catheter ablation of premature ventricular contractions originating in the right ventricular outflow tract.

OBJECTIVES: To evaluate if radiofrequency catheter ablation is an effective procedure for the treatment of right ventricular outflow tract premature ventricular contractions (RVOT-PVC) and ascertain if it results in an improvement of symptoms. METHODS: A prospective study with 30 consecutive patients (mean age 40 +/- 13 years, 25 females), with no apparent structural cardiopathy, with very frequent (mean density of 1,263 +/- 593/h) RVOT-PVC, symptomatic for more than one year (mean = 74 months) and resistant to antiarrhythmic drugs (3 +/- 1.7, including beta-blockers), who underwent radiofrequency catheter ablation. RESULTS: After the first procedure, there were 23 initial successful cases (76.6%) and 7 initial failures (23.4%). Four patients experienced relapses, two of whom did not undergo the second procedure. The second procedure was carried out in 9 patients (7 initial failures and 2 relapses), and there was success in 5 additional patients, one of them by epicardial access. The final success rate was 80% (24/30), and there were no major complications. After a mean follow-up of 14 +/- 6 months, in the successful group there was a reduction greater than 90% in density of premature ventricular contractions (PVC) (24/24; p<0.0001) and a resulting absence of symptoms in the majority of patients (23/24; p<0.001). CONCLUSION: Radiofrequency catheter ablation is a safe and effective treatment for patients with persistent and symptomatic PVC with RVOT morphology.

Ablation of typical atrial flutter: a prospective randomized study of cooled-tip versus 8-mm-tip catheters.

OBJECTIVES: Both ablation catheters with closed irrigated system and 8mm tip-catheters have been shown to be more effective for typical atrial flutter radiofrequency (RF) ablation when compared to conventional 4 mm tip catheter. Considering the differences in complexity and costs of both systems, a prospective study was designed to compare the efficacy and safety of cooled-tip and 8mm-tip catheters for atrial flutter ablation. METHODS: Fifty-two consecutive patients underwent RF ablation of cavotricupsid isthmus (CTI) for the treatment of typical atrial flutter, using catheter with closed irrigation system (n=26) or 8 mm-tip catheter (n=26). The RF pulses were applied point-by-point for 60 seconds, with power limited at 50 w for the irrigated catheter and by temperature control (60 degrees/70 w) for the 8 mm catheter. RESULTS: The CTI block was successfully performed in 98.1%. Four patients in the irrigated group needed to switch to the other group. There was no significant difference with regard to ablation parameters, such as total time of RF ablation (591.1+/-309.0 s vs 486.2+/-250.8 s), total procedure duration (86.4+/-23.6 vs 78.1+/-22.5 min) and time of fluoroscopy (17.0+/-6.7 vs 15.4+/-4.6 min). During follow-up of 10.6 months in average, one patient in the irrigated group had recurrence of typical atrial flutter. CONCLUSION: Efficacy and safety of CTI ablation was comparable between both techniques (irrigated catheter and 8 mm-tip catheter). The complexity of irrigated catheter makes it less competitive.

Ablação com radiofreqüência de extra-sístoles da via de saída do ventrículo direito / Radiofrequency catheter ablation of premature ventricular contractions originating in the right ventricular outflow tract

OBJETIVOS: Avaliar se a ablação com radiofreqüência é um procedimento eficiente para o tratamento das extra-sístoles da via de saída do ventrículo direito (EVSVD), e se resulta em melhora dos sintomas. MÉTODOS: Estudo prospectivo, com 30 pacientes consecutivos (idade média de 40±13 anos, 25 do sexo feminino), sem cardiopatia estrutural aparente, com EVSVD, muito freqüentes (densidade média de 1.263±593/h), sintomáticos por mais de 1 ano (média =74 meses) e refratários aos fármacos antiarrítmicos (3±1,7, incluindo os beta-bloqueadores), que foram submetidos à ablação com radiofreqüência. RESULTADOS: Após o primeiro procedimento, houve 23 sucessos iniciais (76,6 por cento) e 7 iniciais insucessos (23,4 por cento). Quatro pacientes tiveram recorrências, sendo que dois desses não se submeteram ao segundo procedimento. O segundo procedimento foi realizado em 9 pacientes (7 insucessos iniciais e 2 recorrências), e o sucesso ocorreu em 5 pacientes adicionais, sendo 1 caso por acesso epicárdico. A taxa de sucesso final foi de 80 por cento (24/30), e nenhuma complicação maior ocorreu. Após um seguimento médio de 14±6 meses, no grupo de sucesso final houve uma redução de mais de 90 por cento na densidade das extra-sístoles(24/24; p<0,0001) e resultante ausência de sintomas na maioria dos pacientes (23/24; p<0,001). CONCLUSÃO: A ablação com radiofreqüência é um tratamento seguro e eficaz para os pacientes com extra-sístoles persistentes e sintomáticas com morfologia do trato de saída do ventrículo direito.

OBJECTIVES: To evaluate if radiofrequency catheter ablation is an effective procedure for the treatment of right ventricular outflow tract premature ventricular contractions (RVOT-PVC) and ascertain if it results in an improvement of symptoms. METHODS: A prospective study with 30 consecutive patients (mean age 40 ± 13 years, 25 females), with no apparent structural cardiopathy, with very frequent (mean density of 1,263 ± 593/h) RVOT-PVC, symptomatic for more than one year (mean = 74 months) and resistant to antiarrhythmic drugs (3 ± 1.7, including beta-blockers), who underwent radiofrequency catheter ablation. RESULTS: After the first procedure, there were 23 initial successful cases (76.6 percent) and 7 initial failures (23.4 percent). Four patients experienced relapses, two of whom did not undergo the second procedure. The second procedure was carried out in 9 patients (7 initial failures and 2 relapses), and there was success in 5 additional patients, one of them by epicardial access. The final success rate was 80 percent (24/30), and there were no major complications. After a mean follow-up of 14 ± 6 months, in the successful group there was a reduction greater than 90 percent in density of premature ventricular contractions (PVC) (24/24; p<0.0001) and a resulting absence of symptoms in the majority of patients (23/24; p<0.001). CONCLUSION: Radiofrequency catheter ablation is a safe and effective treatment for patients with persistent and symptomatic PVC with RVOT morphology.

Ablação do flutter atrial típico: estudo prospectivo e randomizado do cateter irrigado fechado versus cateter com eletrodo distal de 8 mm / Ablation of typical atrial flutter: a prospective randomized study of cooled-tip versus 8-mm-tip catheters

OBJETIVOS: Trabalho prospectivo, randomizado para comparar a eficácia e a segurança do cateter irrigado em relação ao cateter com eletrodo distal de 8 mm para ablação com radiofreqüência (RF) do flutter atrial. MÉTODOS: Em 52 pacientes consecutivos referidos para tratamento do flutter atrial típico, a ablação do istmo cavotricuspídeo (Ist-CT) foi realizada com cateter de irrigação fechada (n=26) ou com cateter de eletrodo distal de 8 mm (n=26). Os pulsos de RF foram aplicados ponto a ponto por 60 segundos com potência limitada a 50 w com o cateter irrigado e por controle de temperatura (60°C, 70 w) com cateter de 8 mm. O critério de fim do procedimento foi a obtenção de bloqueio bidirecional do Ist-CT. RESULTADOS: O bloqueio Ist-CT foi obtido em 98,1 por cento dos pacientes. O "crossover" ocorreu em quatro pacientes do grupo com cateter irrigado. Não se encontrou diferença estatística significante em relação aos parâmetros da ablação, tais como tempo total de aplicação de RF (591,1±309,0s vs 486,2±250,8s), duração do procedimento (86,4 ± 23,6 vs 78,1±22,5min) e tempo de fluoroscopia (17,0±6,7 vs 15,4±4,6min) entre os dois grupos. Durante seguimento médio de 10,6 meses, um paciente do grupo irrigado apresentou recorrência do flutter atrial típico. CONCLUSÃO: A ablação do Ist-CT resultou ser efetiva e segura para o controle do flutter atrial com ambas as técnicas empregadas (cateter com eletrodo distal de 8 mm e cateter irrigado). A complexidade técnica do cateter irrigado proporciona menor competitividade.

OBJECTIVES: Both ablation catheters with closed irrigated system and 8mm tip-catheters have been shown to be more effective for typical atrial flutter radiofrequency (RF) ablation when compared to conventional 4 mm tip catheter. Considering the differences in complexity and costs of both systems, a prospective study was designed to compare the efficacy and safety of cooled-tip and 8mm-tip catheters for atrial flutter ablation. METHODS: Fifty-two consecutive patients underwent RF ablation of cavotricupsid isthmus (CTI) for the treatment of typical atrial flutter, using catheter with closed irrigation system (n=26) or 8 mm-tip catheter (n=26). The RF pulses were applied point-by-point for 60 seconds, with power limited at 50 w for the irrigated catheter and by temperature control (60°C / 70 w) for the 8mm catheter. RESULTS: The CTI block was successfully performed in 98.1 percent. Four patients in the irrigated group needed to switch to the other group. There was no significant difference with regard to ablation parameters, such as total time of RF ablation (591.1±309.0s vs 486.2±250.8s), total procedure duration (86.4±23.6 vs 78.1±22.5min) and time of fluoroscopy (17.0±6.7 vs 15.4±4.6min). During follow-up of 10.6 months in average, one patient in the irrigated group had recurrence of typical atrial flutter. CONCLUSION: Efficacy and safety of CTI ablation was comparable between both techniques (irrigated catheter and 8mm-tip catheter). The complexity of irrigated catheter makes it less competitive.

Predicting cholesterol, progesterone, and days to ovulation using postpartum metabolic and endocrine measures.

The objective of this study was to examine relationships among metabolic and endocrine factors that may influence ovarian activity during early lactation. Holstein cows (n = 19) were bled twice each week to determine plasma concentrations of insulin (INS), glucose, cholesterol, insulin-like growth factor-1 (IGF-I), and progesterone (P4). Feed intake and milk production were recorded daily while body weights and milk composition were recorded weekly. Relationships among plasma cholesterol and P4, and days to first and second postpartum ovulation were modeled with energy balance (EB), dry matter intake, milk yield and composition, plasma metabolites, and hormones using the backward elimination technique of multivariate regression analysis. Variables that contributed the most to predicting plasma cholesterol concentrations were dry matter intake x SNF using model 1 (production variables) and the square of glucose (i.e., glucose2) using model 3 (plasma hormones and metabolites). For plasma P4 concentrations, EB (model 2, production variables) and IGF-I (model 3, plasma hormones and metabolites) were the major predictors. The production variables EB and percentage of milk lactose were the greatest contributors to the models predicting days to first and second postpartum ovulations, respectively. Of the plasma hormones and metabolites evaluated, IGF-I2 was the most significant predictor of days to first postpartum ovulation, whereas glucose2 and INS were the significant predictors of days to second postpartum ovulation. Plasma IGF-I, glucose, and INS have been implicated in ovarian functions and their significant contributions to these models are consistent with possible important roles in postpartum return to ovarian competence.

Propionibacteria fed to dairy cows: effects on energy balance, plasma metabolites and hormones, and reproduction.

To determine the effect of feeding Propionibacteria on energy balance, milk yield, and composition, metabolites and hormones of early-lactating dairy cows, multiparous Holstein cows were individually fed a total mixed ration from -2 to 12 wk postpartum with no addition (control, n = 10) or with an additional 17 g of Propionibacteria culture daily (Treated, n = 9). Daily feed intake and milk production were recorded. Plasma cholesterol, nonesterified fatty acids (NEFA), leptin, insulin, glucose, insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP), and progesterone concentrations were measured up to twice weekly. Cows fed supplemental Propionibacteria had improved energy balance at wk 1 of lactation and had lower DMI per kg of body weight than control cows on wk 3 to 7, 10, and 12. Cows fed Propionibacteria had a greater percentage of milk protein and solids-not-fat and plasma NEFA concentrations than did control cows only at wk 1 of lactation. Treatment did not affect milk production or percentage of milk fat and lactose. Leptin levels were greater in treated than control cows throughout the study. Plasma glucose, insulin, cholesterol, IGFBP-3, and IGF-I concentrations were not affected by feeding Propionibacteria, but those variables increased with week postpartum. Plasma IGFBP-2 and IGFBP-5 levels decreased with week postpartum. Measures of reproductive and ovarian function did not differ between Propionibacteria-treated and control cows. Feeding Propionibacteria culture to transition and early lactating dairy cows may hold potential for improved milk protein production and metabolic efficiency during early lactation, without affecting reproductive function.

Ovarian action of leptin: effects on insulin-like growth factor-I-stimulated function of granulosa and thecal cells.

To test the hypothesis that leptin signals metabolic information to the reproductive system in cattle by directly affecting IGF-I-induced ovarian cell function, granulosa and thecal cells from bovine ovarian follicles were cultured for 2 d in serum-free medium with added hormones. Recombinant human leptin at 30 and 300 ng/mL had no effect on basal thecal cell steroidogenesis or thecal cell numbers. However, 300 but not 30 ng/mL of leptin attenuated (p < 0.05) luteinizing hormone-induced androstenedione production by 24% in the absence of IGF-I and by 16% in the presence of IGF-I. Leptin had no effect on IGF-I-induced estradiol production in the presence of follicle-stimulating hormone (FSH), but at 100 ng/mL, leptin inhibited (p < 0.05) FSH plus IGF-I-induced progesterone production and granulosa cell proliferation by 29 and 31%, respectively. Leptin did not compete for 125I-IGF-I binding to granulosa or thecal cells, whereas unlabeled IGF-I did. In conclusion, leptin has weak inhibitory effects on gonadotropin- and/or IGF-I-induced steroidogenesis of thecal and granulosa cells.

Fibrilaçäo atrial - novas drogas antiarritmicas: dofetilida, ibutilida e azimilida / Atrial fibrilation - new antiarrhythmic drugs: dofetilide, ibutilide and azimilide

O sucesso parcial do tratamento näo farmacológico da fibrilaçäo atrial (ablaçäo por catéter, cirurgia e desfibrilador atrial implantável) o excesso da mortalidade relacionado aos antiarritmicos da classe I, assim como os efeitos colaterais indesejáveis das drogas tradicionais do grupo II (amiodarona e sotalol racêmico) tem motivado o desenvolvimento de novos fármacos antiarritmicos. Recentemente 3 novos agentes do grupo II (puros ou de 2a. geraçäo), a dofetilida, a ibotulida e a azimilida foram aprovadas para uso clínico e tem se mostrado promissores no tratamento da fibrilaçäo e do fluttler atriais, especialmente no que se refere à reversäo do flutter atrial ao ritmo sinusal. Entretanto, este efeito antiarritmico favorável em parte, é contrabalanceado pela incidência näo desprezível, de pró-arritmia, especialmente, torsades de pointers, tal fato se deve ao efeito bloqueador seletivo no componente rápido da corrente retificadora tardia do potássio, próprio dos antiarritmicos de classe II puros, dofetilida e ibutilida. A azimilida, devido à sua açäo bloqueadora näo seletiva dos canais de potássio (componentes rápido e lento) apresenta menor potencial de pró-arritmia e desponta como o fármaco mais promissor no manuseio da fibrilaçäo atrial. Estudos randomizados a longo prazo deveräo fornecer maiores informaçöes para o uso racional destas novas drogas.

Adipose obese gene product, leptin, inhibits bovine ovarian thecal cell steroidogenesis.

Leptin, a recently-discovered hormonal product of the obese (ob) gene, circulates in the blood at levels paralleling those of fat reserves and regulates satiety. Although noninsulin-dependent diabetics are insulin-resistant and have greater levels of leptin than normal subjects, little evidence existed previously to support the notion that leptin can influence insulin action, particularly in the ovary. Therefore, we tested the hypothesis that leptin signals metabolic information to the reproductive system by directly affecting insulin-induced thecal cell function. Thecal cells from bovine ovarian follicles were cultured for 2 days in the presence of 10% fetal calf serum, and then cultured for an additional 2 days in serum-free medium with added hormones. Doses of 10 to 300 ng/ml of leptin increased (p < 0.05) insulin-induced proliferation of thecal cells by 8% to 16%. In contrast, leptin blocked (p < 0.05) insulin-induced progesterone and androstenedione production by thecal cells. Insulin and leptin had no effect (p > 0.10) on thecal cell viability. Specific high-affinity, low-capacity binding of 125I-leptin was also demonstrable in thecal cells. Furthermore, leptin did not compete for [125I]insulin binding to thecal cells, whereas unlabeled insulin did. In conclusion, leptin can directly attenuate insulin-induced steroidogenesis of thecal cells while stimulating proliferation of the same cell type. This inhibitory effect of leptin on steroidogenesis does not appear to be mediated through inhibiting binding of insulin to its receptor but rather appears to be mediated through leptin binding to its own receptor. These results provide evidence for a role of leptin as a metabolic signal to the reproductive system via direct action in the ovary.

The adipose obese gene product, leptin: evidence of a direct inhibitory role in ovarian function.

Leptin, a recently-discovered hormonal product of the obese gene, circulates in the blood at levels paralleling those of fat reserves and regulates satiety and improves reproductive performance if injected into mice lacking circulating leptin. Therefore, we tested the hypothesis that leptin signals metabolic information to the reproductive system by directly affecting granulosa cell function. Doses of 10-300 ng/ml leptin had no effect (P > 0.10) on basal or insulin-induced numbers of granulosa cells cultured from small (1-5 mm) or large (> or = 8 mm) bovine follicles. Similarly, 30 and 300 ng/ml leptin had no effect (P > 0.10) on basal estradiol production. However, leptin, in a dose-dependent manner, inhibited (P < 0.05) insulin-induced progesterone and estradiol production by granulosa cells from small and large follicles. Leptin did not compete for specific 125I-insulin binding to granulosa cells. Furthermore, specific binding of 125I-leptin was demonstrable in granulosa cells. In conclusion, leptin, at physiological levels, can directly attenuate insulin-induced steroidogenesis of granulosa cells without affecting proliferation of this ovarian cell type. These results provide evidence to support the hypothesis that leptin can act as a metabolic signal to the reproductive system via direct action at the ovarian level.