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1.
Adv Exp Med Biol ; 903: 17-28, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27343086

RESUMO

Epidemiological studies have shown an association between pathologic events occurring during fetal/perinatal life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called developmental origin of adult disease hypothesis. More recently, evidence has been provided that the pulmonary circulation is also an important target for the developmental programming of adult disease in both experimental animal models and in humans. Here we will review this evidence and provide insight into mechanisms that may play a pathogenic role.


Assuntos
Vasos Sanguíneos/embriologia , Vasos Sanguíneos/fisiopatologia , Desenvolvimento Fetal , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Hipóxia/complicações , Hipóxia/fisiopatologia , Animais , Meio Ambiente , Humanos , Modelos Biológicos
2.
Circulation ; 125(15): 1890-6, 2012 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-22434595

RESUMO

BACKGROUND: Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring. METHODS AND RESULTS: We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7 ± 1.6% versus 8.6 ± 1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally. CONCLUSIONS: Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.


Assuntos
Circulação Pulmonar , Técnicas de Reprodução Assistida/efeitos adversos , Doenças Vasculares/etiologia , Adolescente , Adulto , Artéria Braquial/fisiologia , Espessura Intima-Media Carotídea , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Vasodilatação
3.
Artigo em Inglês | MEDLINE | ID: mdl-37202183

RESUMO

BACKGROUND AND OBJECTIVES: Patients with anti-GABA-A receptor encephalitis characteristically experience therapy-refractory epileptic seizures. General anesthesia is often required to terminate refractory status epilepticus. The immunologic mechanisms leading to antibody formation remain to be elucidated. Described triggers of anti-GABA-A autoimmunity are tumors, mainly thymomas, and herpes simplex encephalitis. METHODS: We present a young woman with prediagnosis of relapse remitting multiple sclerosis (MS), treated with interferons, natalizumab, and alemtuzumab. Six months after one and only cycle of alemtuzumab, speech arrest and behavioral changes with aggressive and anxious traits appeared. She showed increasing motor convulsions resulting in focal status epilepticus. RESULTS: Anti-GABA-A receptor antibodies in CSF and serum were confirmed in different external laboratories, in a more extensive analysis after antibodies against NMDAR, CASPR2, LGI1, GABABR, and AMPAR were ruled out during in-house examination. Clinical condition improved temporarily with cortisone therapy, plasmapheresis, and IVIG but deteriorated rapidly after steroid discontinuation, resulting in brain biopsy. On histopathologic confirmation consistent with anti-GABA-A receptor antibody-associated CNS inflammation, completing the first rituximab cycle, continuing oral corticosteroids and supplementing immunosuppression with cyclosporine A led to quick recovery. DISCUSSION: Our case describes a severe autoantibody-induced encephalitis in a young patient with MS, with alemtuzumab as a potential trigger for anti-GABA-A receptor encephalitis.


Assuntos
Encefalite , Epilepsia Parcial Contínua , Esclerose Múltipla , Estado Epiléptico , Feminino , Humanos , Epilepsia Parcial Contínua/etiologia , Epilepsia Parcial Contínua/terapia , Alemtuzumab/efeitos adversos , Receptores de GABA-A , Esclerose Múltipla/complicações
4.
Am J Physiol Heart Circ Physiol ; 302(12): H2646-53, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22523248

RESUMO

High-altitude destinations are visited by increasing numbers of children and adolescents. High-altitude hypoxia triggers pulmonary hypertension that in turn may have adverse effects on cardiac function and may induce life-threatening high-altitude pulmonary edema (HAPE), but there are limited data in this young population. We, therefore, assessed in 118 nonacclimatized healthy children and adolescents (mean ± SD; age: 11 ± 2 yr) the effects of rapid ascent to high altitude on pulmonary artery pressure and right and left ventricular function by echocardiography. Pulmonary artery pressure was estimated by measuring the systolic right ventricular to right atrial pressure gradient. The echocardiography was performed at low altitude and 40 h after rapid ascent to 3,450 m. Pulmonary artery pressure was more than twofold higher at high than at low altitude (35 ± 11 vs. 16 ± 3 mmHg; P < 0.0001), and there existed a wide variability of pulmonary artery pressure at high altitude with an estimated upper 95% limit of 52 mmHg. Moreover, pulmonary artery pressure and its altitude-induced increase were inversely related to age, resulting in an almost twofold larger increase in the 6- to 9- than in the 14- to 16-yr-old participants (24 ± 12 vs. 13 ± 8 mmHg; P = 0.004). Even in children with the most severe altitude-induced pulmonary hypertension, right ventricular systolic function did not decrease, but increased, and none of the children developed HAPE. HAPE appears to be a rare event in this young population after rapid ascent to this altitude at which major tourist destinations are located.


Assuntos
Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Artéria Pulmonar/fisiologia , Função Ventricular Direita/fisiologia , Adolescente , Doença da Altitude/diagnóstico por imagem , Doença da Altitude/fisiopatologia , Criança , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Masculino , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/fisiopatologia , Ultrassonografia
5.
Circulation ; 122(5): 488-94, 2010 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-20644018

RESUMO

BACKGROUND: Adverse events in utero may predispose to cardiovascular disease in adulthood. The underlying mechanisms are unknown. During preeclampsia, vasculotoxic factors are released into the maternal circulation by the diseased placenta. We speculated that these factors pass the placental barrier and leave a defect in the circulation of the offspring that predisposes to a pathological response later in life. The hypoxia associated with high-altitude exposure is expected to facilitate the detection of this problem. METHODS AND RESULTS: We assessed pulmonary artery pressure (by Doppler echocardiography) and flow-mediated dilation of the brachial artery in 48 offspring of women with preeclampsia and 90 offspring of women with normal pregnancies born and permanently living at the same high-altitude location (3600 m). Pulmonary artery pressure was roughly 30% higher (mean+/-SD, 32.1+/-5.6 versus 25.3+/-4.7 mm Hg; P<0.001) and flow-mediated dilation was 30% smaller (6.3+/-1.2% versus 8.3+/-1.4%; P<0.0001) in offspring of mothers with preeclampsia than in control subjects. A strong inverse relationship existed between flow-mediated dilation and pulmonary artery pressure (r=-0.61, P<0.001). The vascular dysfunction was related to preeclampsia itself because siblings of offspring of mothers with preeclampsia who were born after a normal pregnancy had normal vascular function. Augmented oxidative stress may represent an underlying mechanism because thiobarbituric acid-reactive substances plasma concentration was increased in offspring of mothers with preeclampsia. CONCLUSIONS: Preeclampsia leaves a persistent defect in the systemic and the pulmonary circulation of the offspring. This defect predisposes to exaggerated hypoxic pulmonary hypertension already during childhood and may contribute to premature cardiovascular disease in the systemic circulation later in life.


Assuntos
Hipertensão Pulmonar/etiologia , Hipóxia/etiologia , Doenças Vasculares Periféricas/etiologia , Pré-Eclâmpsia/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adolescente , Fatores Etários , Monóxido de Carbono/metabolismo , Criança , Ecocardiografia Doppler , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Masculino , Estresse Oxidativo/fisiologia , Doenças Vasculares Periféricas/fisiopatologia , Gravidez , Pressão Propulsora Pulmonar/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vasodilatação/fisiologia , Pressão Ventricular/fisiologia , Adulto Jovem
6.
J Cardiovasc Electrophysiol ; 22(6): 638-46, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21235671

RESUMO

INTRODUCTION: The induction of atrial fibrillation (AF) by pulmonary vein (PV) ectopy is well described. The triggers for these PV ectopy are not so well understood. The intrinsic cardiac autonomic nervous system (ANS) has been suggested as a potential upstream regulator that may cause PV ectopy and atrial fibrillation (AF). We hypothesized that activation of the ANS by high frequency stimulation (HFS) of atrial ganglionated plexi (GP) can initiate PV ectopy. METHODS AND RESULTS: During sinus rhythm in 12 patients undergoing ablation for paroxysmal AF, short bursts of HFS, synchronized to the local atrial refractory period, were delivered at presumed GP sites. Electrograms were recorded from catheters placed in the PV, coronary sinus (CS) and high right atrium (HRA). A total of 112 episodes of HFS were recorded, producing ectopic activity in 91 of 112 (81%) episodes. Of these 91 episodes, there were 46 episodes of isolated single ectopic beats, 5 episodes of double ectopic responses, 24 episodes of ectopy/tachycardia lasting <30 s, and 16 episodes of AF lasting >30 s. In 63 of 91 episodes, the PV catheter was placed adjacent to the stimulated GP, resulting in ectopy recorded earliest in the PV catheter in 48 of 63 (76%) episodes. In one patient, reproducible ectopy was shown to occur following AV nodal conduction delay in response to HFS. Without HFS, neither AV nodal conduction delay nor ectopy occurred. CONCLUSIONS: This study has demonstrated a direct link between activation of the intrinsic cardiac autonomic nervous system and pulmonary vein ectopy in humans.


Assuntos
Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Complexos Cardíacos Prematuros/etiologia , Complexos Cardíacos Prematuros/fisiopatologia , Estimulação Cardíaca Artificial/efeitos adversos , Veias Pulmonares/fisiopatologia , Adulto , Idoso , Fibrilação Atrial/diagnóstico , Complexos Cardíacos Prematuros/diagnóstico , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Cardiovasc Electrophysiol ; 22(11): 1224-31, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21615814

RESUMO

INTRODUCTION: The intrinsic cardiac autonomic nervous system (ANS) is implicated in atrial fibrillation (AF) but little is known about its role in maintenance of the electrophysiological substrate during AF in humans. We hypothesized that ANS activation by high-frequency stimulation (HFS) of ganglionated plexi (GP) increases dispersion of atrial AF cycle lengths (AFCLs) via a parasympathetic effect. METHODS AND RESULTS: During AF in 25 patients, HFS was delivered to presumed GP sites to provoke a bradycardic vagal response and AFCL was continuously monitored from catheters placed in the pulmonary vein (PV), coronary sinus (CS), and high right atrium (HRA). A total of 163 vagal responses were identified from 271 HFS episodes. With a vagal response, the greatest reduction in AFCL was seen in the PV adjacent to the site of HFS (16% reduction, 166 ± 28 to 139 ± 26 ms, P < 0.0001) followed by the PV-atrial junction (9% reduction, 173 ± 21 to 158 ± 20 ms, P < 0.0001), followed by the rest of the atrium (3-7% reduction recorded in HRA and CS). Without a vagal response, AFCL changes were not observed. In 10 patients, atropine was administered in between HFS episodes. Before atropine administration, HFS led to a vagal response and a reduction in PV AFCL (164 ± 28 to 147 ± 26 ms, P < 0.0001). Following atropine, HFS at the same GP sites no longer provoked a vagal response, and the PV AFCL remained unchanged (164 ± 30 to 166 ± 33 ms, P = 0.34). CONCLUSIONS: Activation of the parasympathetic component of the cardiac ANS may cause heterogenous changes in atrial AFCL that might promote PV drivers.


Assuntos
Fibrilação Atrial/fisiopatologia , Estimulação Cardíaca Artificial , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/fisiopatologia , Sistema Nervoso Parassimpático/fisiopatologia , Adulto , Idoso , Análise de Variância , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Nó Atrioventricular/inervação , Atropina , Cateterismo Cardíaco , Ablação por Cateter , Feminino , Gânglios Parassimpáticos/fisiopatologia , Átrios do Coração/inervação , Sistema de Condução Cardíaco/cirurgia , Frequência Cardíaca , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Parassimpatolíticos , Valor Preditivo dos Testes , Veias Pulmonares/inervação
9.
Chest ; 134(5): 996-1000, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18641102

RESUMO

Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.


Assuntos
Altitude , Expiração/fisiologia , Hipertensão Pulmonar/etnologia , Óxido Nítrico/metabolismo , Pressão Propulsora Pulmonar/fisiologia , Adaptação Fisiológica , Adolescente , Ar/análise , Bolívia/epidemiologia , Criança , Pré-Escolar , Europa (Continente)/etnologia , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Incidência , Lactente , Masculino , Fatores de Risco
10.
Europace ; 10(3): 289-93, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18230600

RESUMO

AIMS: Multiple arrhythmia re-inductions were recently shown in His-Purkinje system (HPS) ventricular tachycardia (VT). We hypothesized that HPS VT was a frequent mechanism of repetitive or incessant VT and assessed diagnostic criteria to select patients likely to have HPS VT. METHODS AND RESULTS: Consecutive patients with clustering VT episodes (>3 sustained monomorphic VT within 2 weeks) were included in the analysis. HPS VT was considered plausible in patients with (i) impaired left ventricular function associated with dilated cardiomyopathy or valvular heart disease; or (ii) ECG during VT similar to sinus rhythm QRS or to bundle-branch block QRS. HPS VT was plausible in 12 of 48 patients and HPS VT was demonstrated in 6 of 12 patients (50%, or 13% of the whole study group). Median VT cycle length was 318 ms (250-550). Catheter ablation was successful in all six patients. CONCLUSION: His-Purkinje system VT is found in a significant number of patients with repetitive or incessant VT episodes, and in a large proportion of patients with predefined clinical or electrocardiographic characteristics. Since it is easily amenable to catheter ablation, our data support the screening of all patients with repetitive VT in this regard and an invasive approach in a selected group of patients.


Assuntos
Fascículo Atrioventricular/fisiopatologia , Ramos Subendocárdicos/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Adulto , Idoso , Ablação por Cateter , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taquicardia Ventricular/cirurgia , Disfunção Ventricular Esquerda/fisiopatologia
11.
Clin Cardiol ; 31(10): 469-71, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18666174

RESUMO

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in young adults. On the basis of histopathological findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bartonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. HYPOTHESIS: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC. METHODS: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls. RESULTS: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (p < or = 0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC. CONCLUSIONS: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bartonella henselae and ARVC, in particular its sporadic (nonfamilial) form.


Assuntos
Angiomatose Bacilar/complicações , Anticorpos Antibacterianos/imunologia , Displasia Arritmogênica Ventricular Direita/etiologia , Bartonella henselae/imunologia , Adulto , Angiomatose Bacilar/diagnóstico , Angiomatose Bacilar/microbiologia , Anticorpos Anti-Idiotípicos/imunologia , Displasia Arritmogênica Ventricular Direita/diagnóstico , Diagnóstico Diferencial , Ecocardiografia , Humanos , Imunoglobulina G/imunologia , Imageamento por Ressonância Magnética , Masculino , Ventriculografia de Primeira Passagem
12.
High Alt Med Biol ; 9(4): 295-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19115913

RESUMO

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.


Assuntos
Aclimatação/fisiologia , Altitude , Pressão Sanguínea/fisiologia , Monitoramento Ambiental , Indígenas Sul-Americanos , População Branca , Adulto , Bolívia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etnologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Óxido Nítrico/metabolismo , Oximetria , Artéria Pulmonar/fisiologia , Fatores de Risco
13.
Swiss Med Wkly ; 137(15-16): 228-33, 2007 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-17525878

RESUMO

QUESTIONS UNDER STUDY: In patients with an implantable defibrillator (ICD), inappropriate ICD interventions alter the quality of life, may cause hospitalisations and limit cost-effectiveness. The aim of the study was to determine the incidence and causes of inappropriate ICD interventions, and to identify patients at risk. METHODS: For this observational longitudinal study, consecutive patients undergoing ICD implantation at the University Hospital of Berne were included in a registry. All stored electrograms of episodes triggering ICD interventions were systematically reviewed and analysed to determine whether ICD interventions were appropriate or inappropriate. Inappropriate ICD interventions were classified according to their cause, and risk factors were sought. RESULTS: 214 consecutive patients were followed during a median time of 2.7 years (3.7 years IQR, 698 patient years). 81 inappropriate ICD interventions occurred in 58 patients (27%). Factors triggering inappropriate ICD interventions included atrial fibrillation and flutter (n = 35, 44%), sinus tachycardia (n = 26, 32%), lead fracture (n = 12), recurrent self-terminating ventricular tachycardia (n = 5), double-counting due to T-wave oversensing (n = 3). The only identifiable risk factor for inappropriate ICD interventions was sustained ventricular tachycardia as index arrhythmia. CONCLUSIONS: An important proportion of ICD patients suffer inappropriate ICD interventions that are most commonly due to supraventricular arrhythmias. Patients with ventricular tachycardia prior to ICD implantation are at higher risk of inappropriate ICD interventions. Interventions aiming at decreasing the risk of inappropriate ICD interventions should be considered in these patients.


Assuntos
Arritmias Cardíacas/terapia , Desfibriladores Implantáveis , Procedimentos Desnecessários/estatística & dados numéricos , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/epidemiologia , Cardioversão Elétrica/estatística & dados numéricos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Suíça
14.
Adv Exp Med Biol ; 588: 277-91, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17089896

RESUMO

Studies of high-altitude populations, and in particular of maladapted subgroups, may provide important insight into underlying mechanisms involved in the pathogenesis of hypoxemia-related disease states in general. Over the past decade, studies involving short-term hypoxic exposure have greatly advanced our knowledge regarding underlying mechanisms and predisposing events of hypoxic pulmonary hypertension. Studies in high altitude pulmonary edema (HAPE)-prone subjects, a condition characterized by exaggerated hypoxic pulmonary hypertension, have provided evidence for the central role of pulmonary vascular endothelial and respiratory epithelial nitric oxide (NO) for pulmonary artery pressure homeostasis. More recently, it has been shown that pathological events during the perinatal period (possibly by impairing pulmonary NO synthesis), predispose to exaggerated hypoxic pulmonary hypertension later in life. In an attempt to translate some of this new knowledge to the understanding of underlying mechanisms and predisposing events of chronic hypoxic pulmonary hypertension, we have recently initiated a series of studies among high-risk subpopulations (experiments of nature) of high-altitude dwellers. These studies have allowed to identify novel risk factors and underlying mechanisms that may predispose to sustained hypoxic pulmonary hypertension. The aim of this article is to briefly review this new data, and demonstrate that insufficient NO synthesis/bioavailability, possibly related in part to augmented oxidative stress, may represent an important underlying mechanism predisposing to pulmonary hypertension in high-altitude dwellers.


Assuntos
Altitude , Hipertensão Pulmonar/diagnóstico , Doença da Altitude/complicações , Pressão Sanguínea , Suscetibilidade a Doenças , Síndrome de Down/complicações , Endotelina-1/metabolismo , Humanos , Hipertensão , Hipertensão Pulmonar/patologia , Modelos Biológicos , Montanhismo , Óxido Nítrico/metabolismo , Policitemia/patologia , Artéria Pulmonar/patologia , Circulação Pulmonar
17.
Pediatrics ; 127(6): e1445-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21536612

RESUMO

OBJECTIVE: Although a history of previous acute mountain sickness (AMS) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure, the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospective controlled study. METHODS: In 27 nonacclimatized children and 29 adults, AMS was assessed during the first 48 hours after rapid ascent to 3450 m on 2 consecutive occasions 9 to 12 months apart. RESULTS: During the first exposure, 18 adults (62%) and 6 children (22%) suffered from AMS; during the second exposure, 14 adults (48%) and 4 children (15%) suffered from this problem (adults versus children, P ≤ .01). Most importantly, the intraindividual reproducibility of AMS was very different (P < .001) between children and adults. None of the 6 children having suffered from AMS during the first exposure suffered from AMS during the second exposure, but 4 children with no AMS during the first exposure did experience this problem during the second exposure. In contrast, 14 of the 18 adults who suffered from AMS on the first occasion also presented with this problem during the second exposure, and no new case developed in those who had not experienced AMS on the first occasion. CONCLUSIONS: In adults, a history of AMS is highly predictable of the disease on subsequent exposure, whereas in children it has no predictive value. A history of AMS should not prompt practitioners to advise against reexposure to high altitude or to prescribe drugs for its prophylaxis in children.


Assuntos
Adaptação Fisiológica , Doença da Altitude/diagnóstico , Prevenção Primária/métodos , Doença Aguda , Adolescente , Adulto , Doença da Altitude/epidemiologia , Doença da Altitude/prevenção & controle , Criança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Suíça/epidemiologia , Adulto Jovem
18.
Int J Cardiol ; 151(1): 58-62, 2011 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-20537415

RESUMO

BACKGROUND: Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Its practical determination by echocardiography remains challenging. We compared routine assessment of lateral tricuspid annular systolic motion velocity (TV(lat), cm/s) using pulsed-wave tissue Doppler imaging from the apical 4-chamber view with cardiac magnetic resonance (CMR) as reference method. METHODS AND RESULTS: 254 individuals (43 ± 18 years) underwent both CMR (contiguous short axis slices; retrogated cine steady state free precession technique; manual contour tracing) and echocardiography within 2 ± 2 months. Seventy-five had coronary artery disease, 87 congenital heart disease, 17 dilated cardiomyopathy, 15 pulmonary artery hypertension, and 47 normal findings. RV ejection fraction (EF) by CMR was 51 ± 12% (range 17-78%). There was a linear correlation between RVEF and TV(lat) (r=0.60; p<0.0001). A TV(lat) cut-off of 12 cm/s identified patients with normal EF (≥50%) with 81% sensitivity and 68% specificity, and a threshold of TV(lat) <9 cm/s identified patients with severely reduced RVEF (<30%) with 82% sensitivity and 86% specificity. CONCLUSIONS: Systolic long-axis velocity measurements of the lateral tricuspid annulus allow a reliable assessment of RVEF in clinical routine. A threshold of TV(lat)<9 cm/s identifies patients with severely reduced RVEF (<30%) with high sensitivity and specificity.


Assuntos
Cardiopatias , Volume Sistólico/fisiologia , Sístole/fisiologia , Valva Tricúspide/fisiologia , Função Ventricular Direita/fisiologia , Adulto , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Ecocardiografia Doppler de Pulso/métodos , Ecocardiografia Doppler de Pulso/normas , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/patologia
19.
J Interv Card Electrophysiol ; 32(2): 163-71, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21647641

RESUMO

PURPOSE: This study aims to evaluate a method to detect heart rate variability (HRV) changes using short ECG segments during ablation for arrhythmias. METHODS: HRV was averaged from sequentially shorter time windows from 5-min ECG recordings in 15 healthy volunteers. The 40-s window was identified as the shortest duration that yielded reproducible values in high frequency (HF) and low frequency (LF) HRV. This method was validated in patients undergoing tilt table testing to see if the expected modulation in HRV that occurs prior to syncope could be detected from multiple 40-s recordings. Lastly, this method was used to assess HRV changes in 75 patients undergoing ablation for atrial fibrillation (AF) and other arrhythmias, to see if autonomic modulation as a result of ablation could be detected. A further 14 patients had stepwise HRV measurements at different stages of the AF ablation procedure to determine whether intra-procedural HRV changes could be detected. RESULTS: HRV, averaged from multiple 40-s recordings, demonstrated the expected increase immediately preceding syncope compared with baseline (LF: 341 ± 311-1,536 ± 1,368 ms(2), p< 0.05; HF: 342 ± 339-1,628 ± 1,755 ms(2), p < 0.05). AF ablation, particularly following right pulmonary vein circumferential ablation, produced immediately detectable reductions in LF (153 ± 251-50 + 116 ms(2), p < 0.001) and HF (86 ± 195-33 ± 83 ms(2), p < 0.001) without any change in RR interval (877 ± 191-843 ± 220 ms, p = 0.261). Ablation for atrial flutter did not change the mean RR interval, LF or HF HRV. CONCLUSION: Averaging multiple 40-s windows give valid HF and LF HRV measurements that enable detection of intra-procedural changes. Left atrial ablation around the right-sided pulmonary veins is unique in producing reductions in HRV. This method has the potential for use as an endpoint marker for adjunctive autonomic ablation procedures.


Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/cirurgia , Ablação por Cateter/métodos , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Monitorização Intraoperatória/métodos , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Teste da Mesa Inclinada , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Prog Cardiovasc Dis ; 52(6): 534-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20417347

RESUMO

About 30 million people live above 2500 m in the Andean Mountains of South America. Among them are 5.5 million Aymaras, an ethnic group with its own language, living on the altiplano of Bolivia, Peru, and northern Chile at altitudes of up to 4400 m. In this high altitude region traces of human population go back for more than 2000 years with constant evolutionary pressure on its residents for genetic adaptation to high altitude. Aymaras as the assumed direct descendents of the ancient cultures living in this region were the focus of much research interest during the last decades and several distinctive adaptation patterns to life at high altitude have been described in this ethnic group. The aim of this article was to review the physiology and pathophysiology of circulatory adaptation and maladaptation to longtime altitude exposure in Aymaras and Caucasians.


Assuntos
Aclimatação , Doença da Altitude/etnologia , Fenômenos Fisiológicos Cardiovasculares , Hipóxia/etnologia , Indígenas Sul-Americanos , Policitemia/etnologia , População Branca , Altitude , Doença da Altitude/sangue , Bolívia/etnologia , Chile/etnologia , Medicina Baseada em Evidências , Humanos , Hipertensão Pulmonar/etnologia , Hipóxia/sangue , Óxido Nítrico/sangue , Peru/etnologia , Circulação Pulmonar , Ventilação Pulmonar , América do Sul/etnologia
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