A Curva Volume-Tempo Obtida pela Ecocardiografia Tridimensional na Cardiomiopatia Chagásica: Análise do Mecanismo das Adaptações Hemodinâmicas / The Volume-Time Curve by Three-Dimensional Echocardiography in Chagas Cardiomyopathy: Insights into the Mechanism of Hemodynamic Adaptations

Resumo Fundamento A ecocardiografia tridimensional (ECO 3D) permite a geração de uma curva volume-tempo representativa das alterações no volume ventricular esquerdo (VE) ao longo de todo o ciclo cardíaco. Objetivo O presente estudo tem como objetivo demonstrar as adaptações hemodinâmicas presentes na cardiomiopatia chagásica (CC) por meio das medidas de volume e fluxo obtidas pela curva volume-tempo por ECO 3D. Métodos Vinte pacientes com CC e 15 indivíduos saudáveis foram incluídos prospectivamente em um estudo de desenho transversal. Realizou-se ECO 3D em todos os indivíduos e as curvas volume-tempo do VE foram geradas. O fluxo foi obtido pela primeira derivada da curva volume-tempo por meio do software MATLAB. A significância estatística foi definida com p<0,05. Resultados Embora os pacientes com CC tivessem menor fração de ejeção do VE em comparação com o grupo controle (29,8±7,5 vs. 57,7±6,1, p<0,001), o volume (61,5±25,2 vs. 53,8±21,0, p=0,364) e o fluxo de ejeção máximo durante a sístole (-360,3±147,5 vs. -305,6±126,0, p = 0,231) mostraram-se semelhantes entre os grupos. Da mesma forma, o fluxo máximo na fase de enchimento inicial e durante a contração atrial mostrou-se semelhante entre os grupos. Um aumento na pré-carga expressa pelo volume diastólico final do VE (204,8±79,4 vs. 93,0±32,6), p<0,001) pode manter o fluxo e o volume ejetado semelhantes aos dos controles. Conclusão Com uma ferramenta não invasiva, demonstramos que o aumento no volume diastólico final do VE pode ser o principal mecanismo de adaptação que mantém o fluxo e o volume ejetado no cenário de disfunção sistólica ventricular esquerda severa.

Abstract Background Three-dimensional echocardiography (3D ECHO) allows the generation of a volume-time curve representative of changes in the left ventricular (LV) volume throughout the entire cardiac cycle. Objective This study aims to demonstrate the hemodynamic adaptations present in Chagas cardiomyopathy (CC) by means of the volume and flow measurements obtained by the volume-time curve by 3D ECHO. Methods Twenty patients with CC and 15 healthy subjects were prospectively enrolled in a cross-sectional design study. 3D ECHO was performed in all subjects and the volume over time curves of the LV was generated. The flow was obtained by the first derivative of the volume-time curve using the software MATLAB. Statistical significance was set at p<0.05. Results Although CC patients had lower LV ejection fraction compared to the control group (29.8±7.5 vs. 57.7±6.1, p<0.001), stroke volume (61.5±25.2 vs. 53.8±21.0, p=0.364) and maximum ejection flow during systole (-360.3±147.5 vs. -305.6±126.0, p=0.231) were similar between the groups. Likewise, the maximum flow in the early diastolic filling phase and during atrial contraction was similar between groups. An increase in preload expressed by LV end diastolic volume (204.8±79.4 vs. 93.0±32.6), p<0.001) may maintain the flow and stroke volumes similar to the controls. Conclusion Using a non-invasive tool, we demonstrated that an increase in LV end-diastolic volume may be the main adaptation mechanism that maintains the flow and stroke volumes in the setting of severe LV systolic dysfunction.

Otto Frank y Ernest Starling. Más allá de una ley o un mecanismo. Breve reseña histórica / Otto Frank and Ernest Starling. Beyond a law or a mechanism. Brief historical relate

Resumen La ley o mecanismo de Frank-Starling describe la relación entre la longitud inicial de las fibras miocárdicas y la fuerza generada por su poder de contracción. Aunque ni Otto Frank (1895) como tampoco Ernest Starling (1915) fueron los primeros en descubrir que el volumen diastólico final regula el trabajo del corazón, su participación para este famoso epónimo fisiológico es indiscutible, y de ahí que sus nombres perduraran por más de un siglo en el ambiente de la fisiología, la cardiología y los cuidados intensivos, entre otras disciplinas. Se revisa la biografía de Otto Frank (1865-1944), un excepcional fisiólogo alemán con un amplio conocimiento en física, matemáticas y ciencias naturales, que formuló principios teóricos para la fisiología muscular y cardiovascular, además de muchas otras contribuciones metodológicas e instrumentales. También se examina la vida del gran médico y fisiólogo inglés Ernest Henry Starling (1866-1927), quien elaboró diversos y relevantes aportes científicos, más allá de sus afamadas publicaciones sobre la función circulatoria. Finalmente, el presente artículo comenta en forma breve sus principales y más importantes contribuciones, así como también aspectos menos conocidos de sus logros científicos.

Abstract Frank-Starling's law or mechanism describes the relationship between the initial length of myocardial fibers and the force generated by their contraction power. Although neither Otto Frank (1895) nor Ernest Starling (1915) were the first to discover that the final diastolic volume regulates the work of the heart, their participation for this famous physiological eponym is indisputable, enduring their names for more than a century in the environment of physiology, cardiology and intensive care, among other disciplines. The biography of Otto Frank (1865-1944) is reviewed, who was an exceptional German physiologist with extensive knowledge in physics, mathematics and natural sciences who formulated theoretical principles for muscular and cardiovascular physiology, in addition to many other methodological contributions in instrumentals. Also examined the life of the great English physician and physiologist Ernest Henry Starling (1866-1927), who produced various and relevant scientific contributions, beyond his famous publications on circulatory function. Finally, this article briefly comments on its main and most important contributions, as well as less known aspects of its scientific achievements.

How experiments on single capillaries help us to understand the circulation as a whole.

After a brief summary of the discovery of the microcirculation, this review looks at two classical series of papers published during the first 30 years of the 20th century by Krogh and Landis, and then discusses how, over the last 30 years of the century, some of these ideas have been developed by experiments on single microvessels. The topics covered include the recruitment of capillaries during functional hyperaemia, the identification of pressure gradients in the circulation and hence the sites of vascular resistance, the confirmation of Starling’s principle of fluid exchange and the development of new ideas about microvascular fluid exchange and, how the phenomenon of flow sensitive permeability to small diffusible molecules has been discovered.

El centenario de las hormonas: Un recuerdo de Ernest H. Starling y William M. Bayliss / On the centennial of hormones: A tribute to Ernest H. Starling and William M. Bayliss

En junio de 2005 se cumplió el primer centenario de la introducción de la palabra hormona para definir al mensajero químico que originado en un tejido viaja a través de la circulación para alcanzar otro tejido distante y ejercer un efecto específico. Ernest H. Starling presentó en junio de 1905 las Conferencias Croone en las que desarrolló la teoría del control químico del organismo como una culminación de sus previas investigaciones que había realizado en colaboración con el fisiólogo William M. Bayliss sobre la fisiología del corazón, el intercambio capilar, la reabsorción tubular del glomérulo renal y el peristaltismo intestinal. La primera hormona recibió el nombre de secretina y su descubrimiento desencadenó un incontable número de investigaciones multidisciplinarías que han permitido el avance en el conocimiento de la biología molecular y particularmente en el área de la endocrinología.

Ernest H. Starling introduced the term hormone 100 years ago in his Croonian Lectures to the Royal College of Physicians in June 1905. It was demonstrated for the first time that one part of the body could influence the function of another distant part. Starling for the first time suggested the word hormone. This review attempts to trace the development of studies in endocrinology, beginning in the middle of the nineteenth century. Starling discovered secretin, the first hormone, in collaboration with William M. Bayliss, and they introduced the hormone concept with recognition of chemical regulation. Thus the name hormone sparked multidisciplinary research in endocrinology and molecular biology, which shed light on the chemical communication within the organism.

Influência da elevação sustentada da pressão arterial sobre a dP/dt do ventrículo esquerdo mantendo-se constante a pressão diastólica do ventriículo esquerdo / Influence of Sustained Elevations of Arterial Pressure on the Left Ventricular dP/dt Keeping Constant the Left Ventricular end Diastolic Pressure

PURPOSE: To evaluate the influence of sustained elevations of arterial pressure on dP/dt values, while the left ventricular end diastolic pressure was kept constant. METHODS: Thirteen anesthetized dogs, mechanically ventilated and submitted to thoracotomy and pharmacological autonomic block (atropine-0.5 mg/kg i.v. + oxprenolol-3 mg/kg i.v.) were studied. The arterial pressure elevation was obtained by mechanical constriction of the descending thoracic aorta. Analyses were made in control (C) situation and after two successive increments of arterial pressure, sustained for 10 min, called hypertension 1 (H1) and hypertension 2 (H2), respectively. The end diastolic left ventricular pressure was kept constant by utilization of a perfusion system connected to the left atria. RESULTS: Heart rate did not change (C: 125 +/- 13.9 bpm; H1: 125 +/- 13.5 bpm; H2: 123 +/- 14.1 bpm; p > 0.05); the LVSP increased (C: 119 +/- 8.1 mmHg; H1: 142 +/- 7.9 mmHg; H2: 166 +/- 7.7 mmHg; p < 0.01); the AoDP increased (C: 89 +/- 11.6 mmHg; H1: 99 +/- 9.5 mmHg; H2: 120 +/- 11.8 mmHg; p < 0.01); the LVEDP (C: 6.2 +/- 2.48 mmHg; H1: 6.3 +/- 2.43 mmHg; H2:6.1 +/- 2.51 mmHg; p > 0.05) and the dP/dt (C: 3068 +/- 1057.1 mmHg/s; H1: 3112 +/- 995.7 mmHg/s; H2: 3086 +/- 979.5 mmHg/s; p > 0.05) did not change. CONCLUSION: dP/dt values are not influenced by a sustained elevation of arterial pressure, when the end diastolic left ventricular pressure is kept constant.

Influência da elevaçäo transitória e da elevaçäo sustentada da pressäo arterial sobre a primeira derivada temporal da pressäo ventricular / Influence of transient and sustained elevations of arteri al pressure on the left ventricular rate of pressure rise

Objetivo - Avaliar a influência de elevaçöes transitórias e de elevaçöes sustentadas da pressäo arterial (PA) sobre a primeira derivada temporal da pressäo ventricular esquerda (dp/dt). Objetivo - Foram estudados 13 cäes anestesiados, toracotomizados, ventilados mecanicamente e submetidos a bloqueio autonômico (oxprenolol 3,0 mg/Kg + atropina 0,5 mg/Kg). A elevaçäo da PA foi obtida por constriçäo mecânica da aorta torácica descendente. Em todos animais estudados foram aplicados dois protocolos: Hipertensäo Arterial Transitória (HAT) e Hipertensäo Arterial Sustentada (HAS). Nas diversas condiçöes dos dois protocolos foram analisadas as seguintes variáveis: freqüência cardíaca (FC); pressäo sistólica (PSVE) e diastólica final (PdVE) do ventrículo esquerdo e a primeira derivada temporal da pressäo ventricular (dp/dt). No protocolo HAT as variáveis foram analisadas na condiçäo basal (To) e no momento em que a PA atingia valor máximo (Tm) durante elevaçäo pressárica fugaz. No protocolo HAS as variáveis foram estudadas na condiçäo basal (Ho) e após duas elevaçöes pressóricas sucessivas sustentadas durante 10 minutos: Hipertenso 1 (H1) e Hipertenso 2 (H2). Resultados - Näo houve variaçäo significante da FC durante todo o experimento. Em HAT a PSVE foi elevada de 133 ñ 22 mmHg para 180 ñ 27 mmHg. Durante HAS os valores da PSVE foram: Ho = 129 ñ 25 mmHg; H1 = 152 ñ 23 mmHg; H2 = 182 ñ 24 mmHg. As elevaçöes pressóricas se acompanharam de elevaçäo da PDFVE. Em HAT a PDFVE elevou-se de 7 ñ 2 mmHg para 13 ñ 2 mmHg (p < 0,05); durante a HAS a PDFVE aumentou (p < 0,05) de 7 ñ 2 mmHg em H1 e para 14 ñ 3 mmHg em H2. Näo houve variaçäo significante da dp/dt durante a HAT (3.303 ñ 598 mmHg/s para 3.350 ñ 653 mmHg/s; p > 0,05) enquanto que em HAS ocorreu aumento significante da dp/dt (Ho = 3.233 ñ 576 mmHg; H1 = 3.831 ñ 667 mmHg/s; H2 = 4.594 ñ 833 mmHg/s; p , 0,05). Conclusäo - Elevaçöes sustentadas da PA resultam em aumento significantes da dp/dt, à medida que se acentua a carga cardíaca. As sobrecargas pressóricas sustentadas desencadeiam ajustes cardíacos, tempo-dependentes, que resultam em estimulaçäo inotrópica, provavelmente, por interferência do mecanismo de Frank-Starling