Responsiveness, affinity constants and beta-adrenoceptor reserves for isoprenaline on aortae from normo-, pre and hypertensive rats

The objective of this study was to determine the responsiveness, affinity constants and beta-adrenoceptor reserves for isoprenaline on the isolated aorta in the maturation of normotensive and hypertensive rats. The effects of a very slowly reversible antagonist, bromoacetylalprenololmenthane (BAAM), on the relaxant responses of the aortae of 5- and 14-week-old Wistar Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHRs) to isoprenaline were determined. Five-week-old SHRs are pre-hypertensive and the aortic rings are less responsive to isoprenaline than age-matched WKY (pD(2) values: WKY, 8.40; SHRs, 8.03). Similar relaxant responses to forskolin were obtained on the aortae of 5- and 14-week-old WKY and SHRs. The K-A value for isoprenaline at the aortic beta(2)-adrenoceptors of the 5-week-old WKY was 2.1 x 10(-7) M, and similar values were obtained on the aortae of 5-week-old SHR and 14-week-old WKY and SHRs. In the maturation of the WKY aortae from 5 to 14 weeks, there was a reduction in the maximum response, a major loss of sensitivity and a loss of 2-adrenoceptor reserve for isoprenaline. On 5-week-old SHR aorta, the sensitivity to isoprenaline was 2.5-fold lower, and the beta(2)-adrenoceptor reserve was less than on age-matched WKY. In the development of hypertension on the SHR aorta from 5 to 14 weeks, there was a reduction in the maximum response to isoprenaline. At 14 weeks, the sensitivity and the 2-adrenoceptor reserve to isoprenaline were similar, but the maximum responses were lower on the SHR than WKY. As there are differences in pre-hypertensive SHR and age-matched WKY aortic responses to isoprenaline, it is no longer valid to consider that the loss of responsiveness to isoprenaline in hypertension is solely owing to the hypertension. There are no changes in affinity, but major changes in the sensitivity, maximum responses and aortic beta(2)-adrenoceptor reserves to isoprenaline in the maturation of normotensive and pre-hypertensive aortae.

Effects of dofetilide on cardiovascular tissues from normo- and hypertensive rats

The aim was to test whether dofetilide has some potential for use in the treatment of heart failure. Dofetilide at less than or equal to 3 x 10(-5) m had no effect on the quiescent Wistar Kyoto (WKY) rat aorta, mesenteric and intralobar arteries, or the spontaneous contractions of the WKY rat portal vein. Dofetilide at 10(-6) to 3 x 10(-5) m relaxed the KCl-contracted aorta. Dofetilide at 10(-9)-10(-7) m augmented the force of contraction of left ventricle strips from 12- and 18-month-old WKY rats at 2 Hz. Spontaneously hypertensive rats (SHRs) at 12 and 17-21 months of age are models of cardiac hypertrophy and failure, respectively. The augmentation of force at 2 Hz with dofetilide was similar on 12- and 18-month-old WKY rats and 12-month-old SHRs but reduced on the 18-month-old SHR left ventricle. At a higher more physiological frequency, 4 Hz, the threshold concentration of dofetilide required to augment the force responses of 21-month-old SHR left ventricles was markedly increased and the maximum augmenting effect was decreased. Dofetilide at 10(-7)-10(-5) m reduced the rate of the 17-month-old WKY rat right atrium, and had a similar effect on age-matched SHR right atrium. In summary, dofetilide is a positive inotrope and negative chronotrope in the rat. However, as the positive inotropic effect is not observed with clinically relevant concentrations at a physiological rate in heart failure, dofetilide is unlikely to be useful as a positive inotrope in the treatment of heart failure.

Surgical programme at Royal Alexandra Hospital, Sydney, for Papua New Guinea children with congenital heart disease, 1978-1994

Objective : To report the history of the Royal Alexandra Hospital for Children (RAHC) Papua New Guinea (PNG) cardiac surgical programme and describe the selection, preoperative clinical features and postoperative outcome of children with congenital heart disease managed by the programme. Methods : Details for each of the PNG cardiac patients admitted to RAHC following selection by visiting cardiologists between 1978 and 1994 were entered into a database, and analysed and interpreted. Results : A congenital heart defect was confirmed in 165 of the 170 children selected. The male to female ratio was 1:1 and the mean age on admission to RAHC was 5.5 years. Almost all of the children for whom data were available (98%) had a weight for age and 41% had a height for age less than the 3rd centile. One-sixth had delayed milestones. A large number were tachypnoeic, in heart failure, or had pulmonary hypertension on admission. Ventricular septal defect and tetralogy of Fallot were the commonest defects, and lesions such as aortic stenosis, coarctation of the aorta and transposition of the great arteries were absent or rare. Thirty-one (19%) of the children selected initially did not receive surgery because of pulmonary hypertension, or because the lesions did not fall within the programme guidelines for operation. One hundred and twenty-nine children had corrective and four had palliative procedures. Half of the operated children had postoperative complications. Eight children died, all following open-heart procedures, giving a case fatality rate of 6%. Preoperative tachypnoea, hepatomegaly, cardiac failure and pulmonary hypertension were strongly associated with poor outcome. Conclusions : The programme was an arduous exercise for all organizations concerned, but achieved comparatively good short-term outcomes. The experience gained should assist in planning for similar programmes.

Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation

Modeling physiological processes using tracer kinetic methods requires knowledge of the time course of the tracer concentration in blood supplying the organ. For liver studies, however, inaccessibility of the portal vein makes direct measurement of the hepatic dual-input function impossible in humans. We want to develop a method to predict the portal venous time-activity curve from measurements of an arterial time-activity curve. An impulse-response function based on a continuous distribution of washout constants is developed and validated for the gut. Experiments with simultaneous blood sampling in aorta and portal vein were made in 13 anesthetized pigs following inhalation of intravascular [O-15] CO or injections of diffusible 3-O[ C-11] methylglucose (MG). The parameters of the impulse-response function have a physiological interpretation in terms of the distribution of washout constants and are mathematically equivalent to the mean transit time ( T) and standard deviation of transit times. The results include estimates of mean transit times from the aorta to the portal vein in pigs: (T) over bar = 0.35 +/- 0.05 min for CO and 1.7 +/- 0.1 min for MG. The prediction of the portal venous time-activity curve benefits from constraining the regression fits by parameters estimated independently. This is strong evidence for the physiological relevance of the impulse-response function, which includes asymptotically, and thereby justifies kinetically, a useful and simple power law. Similarity between our parameter estimates in pigs and parameter estimates in normal humans suggests that the proposed model can be adapted for use in humans.

Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm

Background - Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)- 2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results - Aneurysm tissue was obtained from patients undergoing surgery ( MS: 4 M, 1 F, age 27 - 45 years; BAV: 3 M, 2 F, age 28 - 65 years). Normal aorta from subjects with nonaneurysm disease was also collected ( 4 M, 1 F, age 23 - 93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS ( 27 +/- 8%) and BAV ( 32 +/- 14%) compared with control ( 7 +/- 5%). Conclusions - In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

Potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor in pulmonary and systemic vessels: effects of exposing rats to hypoxia

The aim was to determine whether uptake of 5-hydroxytryptamine (5-HT) by the 5-HT transporter (SERT) modulates contractile responses to 5-HT in rat pulmonary arteries and whether this modulation is altered by exposure of rats to chronic hypoxia (10% oxygen; 8 h/day; 5 days). The effects of the SERT inhibitor, citalopram (100 nM), on contractions to 5-HT were determined in isolated ring preparations of pulmonary artery (intralobar and main) and compared with data obtained in systemic arteries. In intralobar pulmonary arteries citalopram produced a potentiation (viz. an increase in potency, pEC(50)) of 5-HT. The potentiation was endothelium-dependent in preparations from normoxic rats but endothelium-independent in preparations from hypoxic rats. In main pulmonary artery endothelium-independent potentiation was seen in preparations from hypoxic rats but no potentiation occurred in preparations from normoxic rats. In systemic arteries, citalopram caused endothelium-independent potentiation in aorta but no potentiation in mesenteric arteries; there were no differences between hypoxic and normoxic rats. It is concluded that SERT can influence the concentration of 5-HT in the vicinity of the vasoconstrictor receptors in pulmonary arteries. The data suggest that in pulmonary arteries from hypoxic rats, unlike normoxic rats, the SERT responsible for this effect is not in the endothelium and, hence, is probably in the smooth muscle. The data are compatible with reports that, in the pulmonary circulation, hypoxia induces/up-regulates SERT, and hence increases 5-HT uptake, in vascular smooth muscle. The findings may have implications in relation to the suggested use of SERT inhibitors in the treatment of pulmonary hypertension.

Alterations in pulmonary vascular function in rats exposed to intermittent hypoxia

Vasoactive agents were examined in arteries from control rats and rats exposed to intermittent hypoxia (10% oxygen; 8 h/day) for 3, 5 or 20 days. Hypoxic rats developed right ventricular hypertrophy after 5 days, but became pulmonary hypertensive (elevated right ventricular systolic pressure; RVSP) only after 20 days. In pulmonary arteries (main and intralobar), responses to acetylcholine and ionomycin (endothelium-dependent vasodilators) were reduced after 20 and 5 days of intermittent hypoxia, whereas contractions to 5-hydroxytryptamine (5-HT) were enhanced (potency increase >10-fold) after 20, 5 and 3 days. Contractions to endothelin-1 and a thromboxane-mimetic, but not Ca-2divided by, were also increased. No changes in vascular function occurred in aorta. Since changes in pulmonary vascular function preceded the increase in RVSP they do not result from, but may contribute to, the development of hypoxia-induced pulmonary hypertension. If similar changes occur in humans, they may be important in conditions characterised by intermittent, as opposed to continuous, hypoxia. (C) 2003 Elsevier B.V. All rights reserved.

Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice

The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response: 51 ± 8 vs 53 ± 5%, respectively) and SNP-induced vasorelaxation (maximal response: 73 ± 6 vs 74 ± 6%, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm2 x 103). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.

Enfisema subcutâneo e pneumomediastino após amigdalectomia: relato de caso

Várias complicações podem estar relacionadas a procedimentos cirúrgicos na área de cabeça e pescoço. Entre elas, o pneumomediastino, pneumotórax e enfisema subcutâneo ocorrem raramente. Relatamos o caso de uma paciente submetida a tonsilectomia palatina que evoluiu com enfisema subcutâneo da região cervical, torácica e pneumomediastino. Em cirurgias de tonsilas palatinas devem ser observados cuidados com a intubação, uso de máscara sob pressão positiva com oxigênio na recuperação anestésica, atos cirúrgicos intempestivos e uso de aparelhos que proporcionem lesão excessiva na loja tonsiliana a fim de se evitar as complicações descritas.

O tratamento da laringomalácia: experiência em 22 casos

A Laringomalácia é a causa mais comum de estridor na infância, com resolução espontânea até os 2 anos de idade na maioria dos casos. Cerca de 10% dos casos (laringomalácia severa) necessitam de intervenção cirúrgica. O diagnóstico é estabelecido com o exame de videonasofibroscopia, na qual se observa encurtamento da prega ariepiglótica, e/ou excesso de mucosa das aritenóides, e/ou queda da epiglote no sentido ântero-posterior. A etiologia ainda permanece desconhecida. OBJETIVO: Verificar as principais alterações clínicas e anatômicas assim como identificar os principais parâmetros clínicos no acompanhamento e na indicação cirúrgica de pacientes portadores de laringomalácia. FORMA DE ESTUDO: Estudo de coorte transversal. MATERIAL E MÉTODO: Foram incluídos neste estudo 22 crianças com diagnóstico de laringomalácia do ambulatório de otorrinolaringologia pediátrica da UNIFESP-EPM, entre janeiro de 2001 a dezembro de 2003, assistidas pelo mesmo examinador. RESULTADOS: Das 22 crianças com diagnóstico de laringomalácia, duas (9,1%) apresentavam laringomalácia severa com depressão torácica (tórax escavado). O estridor inspiratório e o encurtamento das pregas ariepiglóticas foram encontrados em todos pacientes. À polissonografia, nenhuma criança apresentou evento respiratório significativo durante o sono. As duas crianças com laringomalácia severa foram submetidas à supraglotoplastia com secção das pregas ariepiglóticas. CONCLUSÃO: O estridor respiratório e o encurtamento das pregas ariepiglóticas fazem parte preponderante do quadro clínico. A polissonografia não mostrou ser um parâmetro importante, nem para o acompanhamento clínico nem para a indicação cirúrgica, ao contrário da falta de ganho de peso e da presença de tórax escavado. A secção cirúrgica das pregas ariepiglóticas é efetiva e com baixo índice de morbidade.

Avaliação crítica de 33 pacientes com bócio mergulhante tratados cirurgicamente por cervicotomia

A possibilidade de ser necessário um acesso combinado, com uma incisão cervical e outra torácica, torna o tratamento do bócio mergulhante um desafio tanto no pré quanto no intra-operatório. Discutimos uma padronização da técnica cirúrgica para minimizar a necessidade da abordagem torácica, tornando o bócio mergulhante uma patologia tratável cirurgicamente, por uma única incisão cervical, e com baixos índices de complicações. OBJETIVO: Avaliar a abordagem cirúrgica do bócio mergulhante por cervicotomia e analisar as complicações cirúrgicas. MATERIAL E MÉTODOS: Foi realizada uma coorte histórica com corte transversal por análise retrospectiva dos prontuários de pacientes submetidos à tireoidectomia no período de maio de 2002 a julho de 2007. Um total de 316 pacientes foi submetido à tireoidectomia sendo 33 (10,4%) por bócio mergulhante. RESULTADOS: Todos os 33 pacientes foram tratados cirurgicamente por via cervical sem necessidade de esternotomia. Não foram observadas lesões definitivas de nervo laríngeo inferior ou hipoparatireoidismo definitivo. Apenas 2 pacientes apresentaram paresia de nervo recorrente e 2 pacientes foram reabordados por hematoma cervical. CONCLUSÃO: Pacientes com bócio mergulhante podem ser tratados cirurgicamente por uma única incisão cervical com segurança e baixos índices de complicação.

Corpos estranhos caminham pelo corpo em direção ao coração?

A fixação dos CE, principalmente os pontiagudos, favorece a migração pelo corpo, gerando a expressão popular: "os CEs caminham pelo corpo em direção ao coração". OBJETIVO: Descrever os mecanismos envolvidos na migração do CE e a forma de diagnosticá-los. METODOLOGIA: Numa população de 3.000 casos de corpos estranhos, em 40 anos, foram analisados quatro que tiveram deslocamento extraluminal. Foram tomados os dados clínicos, radiológicos, endoscópicos e ultrassonográficos coletadas no serviço de documentação médica. RESULTADOS: São apresentadas três histórias clínicas em que o CE era de espinha de peixe e uma de cartilagem de peixe. Em todos se analisou o deslocamento. Em dois a migração se iniciou no esôfago, um para a aorta e outro para a região cervical e nos dois outros, o deslocamento ocorreu a partir da faringe: um para a fáscia pré-vertebral e outro se exteriorizou na região submandibular. Discutem os mecanismos pelos quais ocorre a migração dos CEs pelo corpo e os riscos que tais deslocamentos promovem para o paciente e a forma de diagnosticá-los. CONCLUSÕES: Os CE podem caminhar pelo corpo, porém não para o coração. Em casos de histórias arrastadas de ingestão de CEs, o estudo por imagens se faz obrigatório, previamente ao exame endoscópico.

Associação entre achados abreugráficos anômalos do aparelho respiratório e manifestações clínicas

Foram analisados os registros dos principais sintomas de anamnese do aparelho respiratório e de diagnóstico de pneumopatia, nas histórias clínicas de primeira consulta de pacientes com achados anormais do aparelho respiratório na abreugrafia de rotina realizada no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, a partir de 1967. Foram tomados 997 controles (pacientes sem alteração na abreugrafia) pareados com os casos segundo idade e sexo. Em cerca de 1/3 do total de observações clínicas não foi registrada anamnese do aparelho respiratório. Verificou-se maior proporção de registro de sintomas respiratórios e de diagnóstico de pneumopatia entre os casos que entre os controles. O mesmo achado foi verificado para os casos quando os mesmos foram separados em dois grupos de acordo com a maior ou menor gravidade das lesões apresentadas. Hemoptise e dor torácica foram os sintomas que melhor discriminaram doentes de sadios. Recomenda-se que o uso da abreugrafia para diagnóstico de alterações respiratórias seja seletivo, aplicando-se apenas a pacientes com queixas de hemoptise, dor torácica e tosse e/ou expectoração, isoladamente ou combinadas.

A asma induzida pelo exercício na criança

A Asma Brônquica é a doença crónica mais comum nas crianças. É definida como uma disfunção inflamatória crónica das vias aéreas que provoca uma resposta exacerbada das mesmas, levando ao aparecimento recorrente de episódios de pieira, dispneia, opressão torácica e tosse associada a obstrução do fluxo de ar que pode ser reversível, quer de uma forma espontânea quer por terapêutica. Nas crianças, o exercício contínuo e intenso pode levar a um aumento transitório da resistência das vias aéreas, conduzindo a obstrução brônquica ao aparecimento da tosse, pieira, dispneia e opressão torácica, a chamada asma induzida pelo exercício.

Monitorização da insuficiência cardíaca por parâmetros fisiológicos em portadores de cardioversor-desfibrilhador implantável e/ou sistema de ressincronização cardíaca: HF-PREDICT

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular. Área de especialização: Intervenção Cardiovascular.