Fisiología respiratoria: el pulmón al momento de nacer / Respiratory Physiology - the lung at the moment of birth

La adaptación fisiológica de los recién nacidos de la vida intrauterina a la extrauterina incluye cambios fisiológicos complejos. Para que se complete con éxito la transición fetal a neonatal, los recién nacidos deben lograr el aclaramiento de líquido pulmonar, la generación de CRF e inicio de la respiración, para permitir el intercambio de gases y la oxigenación de los tejidos. En este artículo se describen estos mecanismos, algunas bases del desarrollo pulmonar y de la circulación fetal; y las medidas que se requieren para asistir al recién nacido cuando no logran completar esta transición espontáneamente, lo que ocurre en el 5 al 10 % de los casos.

The physiological adaptation of newborns from intrauterine to extrauterine life includes complex physiological changes. For the fetal to neonatal transition to be successfully completed, neonates must achieve lung fluid clearance, FRC generation, and initiation of respiration to allow gas exchange and tissue oxygenation. This article describes these mechanisms, some bases of lung development and fetal circulation; and the measures required to assist the newborn, when they fail to complete this transition spontaneously, which occurs in the 5 to 10% of cases.

Index of microcirculatory resistance: state-of-the-art and potential applications in computational simulation of coronary artery disease / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The dysfunction of coronary microcirculation is an important cause of coronary artery disease (CAD). The index of microcirculatory resistance (IMR) is a quantitative evaluation of coronary microcirculatory function, which provides a significant reference for the prediction, diagnosis, treatment, and prognosis of CAD. IMR also plays a key role in investigating the interaction between epicardial and microcirculatory dysfunctions, and is closely associated with coronary hemodynamic parameters such as flow rate, distal coronary pressure, and aortic pressure, which have been widely applied in computational studies of CAD. However, there is currently a lack of consensus across studies on the normal and pathological ranges of IMR. The relationships between IMR and coronary hemodynamic parameters have not been accurately quantified, which limits the application of IMR in computational CAD studies. In this paper, we discuss the research gaps between IMR and its potential applications in the computational simulation of CAD. Computational simulation based on the combination of IMR and other hemodynamic parameters is a promising technology to improve the diagnosis and guide clinical trials of CAD.

Denervação simpática renal no tratamento da hipertensão arterial resistente: relato de caso / Renal sympathetic denervation in the treatment of resistant arterial hypertension: case report

Introdução: A hipertensão arterial sistêmica (HAS) pode levar a consequências cardiovasculares graves quando não tratadas adequadamente. No entanto, alguns indivíduos, mesmo realizando tratamento recomendado, a pressão arterial (PA) se mantém elevada, passando a ser chamada de hipertensão arterial refratária (HAR). A denervação simpática renal (DSR) é uma terapia amplamente estuda e com resultados promissores que surgiu como alternativa para controlar a PA em pacientes resistentes ao tratamento convencional. Relato de caso: Participante da pesquisa, sexo masculino, 67 anos, com queixa de cefaleia e elevação dos níveis pressóricos. Avaliação cardíaca com alteração apenas da PA (182x113 mmHg), demais sistemas sem variações. Diagnosticado com HAS estágio 3, realizou todas as etapas do tratamento medicamentoso, porém resistente as terapias propostas. Diante do caso, foi diagnosticado com HAR. Sendo realizado DSR que mostrou resultados satisfatórios de redução progressiva da pressão arterial central e periférica. Conclusão: A DSR mostrou-se eficaz no controle gradual e sustentado da PA do participante da pesquisa. Contudo, somente através de estudos clínicos mais amplos e rigorosos será capaz de comprovar a eficácia da DSR no tratamento da PA alta persistente (AU).

Introduction: Systemic arterial hypertension (SHT) can lead to severe cardiovascular outcomes when not properly treated. However, in some individuals, even with recommended treatment, blood pressure (BP) remains high, and is now referred to as Resistant hypertension (RHTN). Renal sympathetic denervation (RDn) is a widely studied and promising therapy that has emerged as an alternative to control BP in patients resistant to conventional treatment. Case report: Research participant, male, 67 years old, complaining of headache and elevated blood pressure. Cardiac assessment with only BP alteration (182x113 mmHg), other systems without variations. Diagnosed with stage 3 hypertension, performed all stages of drug treatment, but resistant to the proposed therapies. Given the case, was diagnosed with RHTN. Being performed RDn that showed satisfactory results of progressive reduction of central and peripheral blood pressure. Discussion: Sympathetic hyperactivity of the renal nervous system releases catecholamines that raise BP. Based on this, the RDn uses a catheter connected to the radiofrequency device that through the femoral artery goes to the two renal arteries and emits energy in the sympathetic fibers attached to the walls of these arteries, destroying them. RDn has been the target of several clinical studies, the best-known being Simplicity HTN-1, 2 and 3 which brought significant and questionable results regarding the efficacy of the procedure. Conclusion: RDn proved to be effective in gradually and sustained BP control of the research participant. However, only through broader and more rigorous clinical studies will it be able to prove the efficacy of RDn in combating persistent high BP (AU).

Fisiología respiratoria: circulación pulmonar / Respiratory physiology: pulmonary circulation

El pulmón recibe sangre desde la circulación bronquial y pulmonar. La circulación pulmonar presenta importantes diferencias con la sistémica, sus vasos sanguíneos poseen características únicas que le permiten cumplir sus diferentes funciones, siendo la más importante el intercambio gaseoso. Existen múltiples factores, activos y pasivos, que están involucrados en la regulación de la resistencia vascular y flujo sanguíneo pulmonar.

The lung receives blood from the bronchial and the pulmonary circulation. The pulmonary circulation presents important differences with the systemic circulation, its blood vessels have unique characteristics that allow them to fulfill their different functions, the most important being gas exchange. There are multiple factors, active and passive, that are involved in the regulation of vascular resistance and pulmonary blood flow.

Uterine vascular resistance and other maternal factors associated with the risk of developing hypertension during pregnancy

Gestational hypertension and pre-eclampsia are important causes of perinatal morbidity. The objective of the present study was to determine the increase in relative risk for developing hypertensive disorders of pregnancy based on the evaluation of pregnant women between 20 and 25 weeks of gestation, and to correlate the findings at this period with the outcome of pregnancy. We conducted a prospective cohort study, with a convenience sample of 1417 patients evaluated at this gestational age, of which 1306 were contacted at childbirth. We detected an increased relative risk of 2.69 (95%CI: 1.86 to 3.89) associated with pulsatility index of the uterine arteries, a 2.8 increase (95%CI: 1.58 to 5.03) in relative risk attributed to maternal age above 35 years, a 1.68 increase (95%CI: 1.17 to 2.40) attributed to parity greater than or equal to 3, and a 5.35 increase (95%CI: 4.18 to 6.85) attributed to chronic hypertension and obesity, with a progressive increase in relative risk according to the degree of overweight, i.e., grades 1, 2, 3, and morbid obesity (2.58, 3.06, 5.84, and 7.28, respectively).

Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy / 中国当代儿科杂志

OBJECTIVE@#To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously.@*RESULTS@#The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (@*CONCLUSIONS@#The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

Fístula arteriovenosa como tratamento adjunto na revascularização arterial do membro em risco / Arteriovenous fistula as adjuvant treatment in arterial revascularization of an at-risk limb

Resumo A oclusão arterial aguda do membro inferior continua sendo um grande desafio para o cirurgião vascular. A abordagem cirúrgica depende principalmente da gravidade da lesão tecidual e da duração dos sintomas. Diversas técnicas estão disponíveis no arsenal terapêutico atual; porém, independentemente da técnica escolhida, fatores pós-operatórios, como o escoamento arterial limitado e o baixo fluxo nos substitutos arteriais, podem contribuir negativamente no resultado da revascularização. Descrevemos um caso de oclusão arterial aguda de membro inferior, no pós-operatório de uma derivação femorotibial, que se encontrava ocluída devido a limitação de escoamento e a alta resistência vascular periférica. Foi submetido a nova revascularização femorotibial, associada à confecção de uma fístula arteriovenosa, seguido de amputação de antepé e enxerto parcial de pele. O investimento enérgico no membro em risco possibilita reduzir os desfechos desfavoráveis, como amputação e óbito, e acelera a recuperação dos tecidos acometidos pela isquemia aguda.

Abstract Acute arterial occlusion remains a major challenge for the vascular surgeon. The therapeutic approach depends mostly upon the severity of the tissue injury and the duration of symptoms. Several techniques are available in the current therapeutic arsenal, however, regardless of the technique chosen, postoperative factors frequently observed, such as poor outflow status, or even low graft flow, can contribute negatively to the outcome of revascularization. We describe a case of acute limb ischemia, in the postoperative period of a femoral-tibial bypass, which was occluded due to outflow limitation and high peripheral vascular resistance. The patient underwent a second tibial revascularization combined with construction of an arteriovenous fistula, followed by forefoot amputation and partial skin graft. An energetic approach to the at-risk limb makes it possible to reduce unfavorable outcomes, such as amputation and death, and accelerates recovery of tissues affected by acute ischemia.

Valores ecobiométricos e índice de resistividade da artéria oftálmica externa em catetos (Tayassu tajacu, Linnaeus, 1758) / [Ecobiometric values and resistivity index of the external ophthalmic artery in collared peccaries (Tayassu tajacu Linnaeus, 1758)]

Foram avaliados ultrassonograficamente, pela via transpalpebral, 28 bulbos oculares de 14 catetos adultos, através de técnica padronizada pelo operador. Adicionalmente foi realizado o estudo hemodinâmico da artéria oftálmica externa pela técnica de Doppler colorido. Os dados coletados foram analisados estatisticamente pelo programa Bioestat 5.0 for Windows, adotando-se 5% de significância. Com a metodologia empregada, obtiveram-se os seguintes valores para os globos oculares direito e esquerdo, respectivamente D1: 1,72 ± 0,29mm e 1,76 ± 0,40mm; D2: 9,95 ± 1,08mm e 10,6 ± 0,99mm; D3: 7,42 ± 0,93mm e 7,45 ± 0,72mm e D4: 17,6 ± 0,78mm e 17,8 ± 0,59mm. Os valores médios do índice de resistividade da artéria oftálmica externa foram 0,435 ± 0,02 e 0,448 ± 0,02 (globos oculares direito e esquerdo, respectivamente). Não houve diferença estatística quanto aos antímeros oculares em nenhum dos parâmetros estudados. Conclui-se que a ecobiometria ocular e a Dopplerfluxometria da artéria oftálmica na espécie Tayassu tajacu é executável e reprodutível, desde que haja domínio do examinador em relação à anatomia e à técnica adequada. Os valores inferidos neste estudo servem de referência para médicos veterinários no diagnóstico de doenças oculares.(AU)

Twenty-eight ocular bulbs of fourteen adult catheters were evaluated through ultrasound with the transpalpebral approach, using a standardized technique by the operator. Additionally, the hemodynamic study of the external ophthalmic artery was performed using the color Doppler technique. The collected data were statistically analyzed by the Bioestat 5.0 for Windows program, adopting 5% of significance. With the methodology employed, the following values were obtained for the right and left eyeballs, respectively D1: 1.72 ± 0.29mm and 1.76 ± 0.40mm; D2: 9.95 ± 1.08mm and 10.6 ± 0.99mm; D3: 7.42 ± 0.93mm and 7.45 ± 0.72mm and D4: 17.6 ± 0.78mm and 17.8 ± 0.59mm. The mean resistivity index values of the external ophthalmic artery were 0.435 ± 0.02 and 0.448 ± 0.02 (right and left eyeball respectively). There was no statistical difference regarding ocular antimers in any of the studied parameters. We concluded that ocular echobiometry and ophthalmic artery Doppler flowmetry in Tayassu tajacu species is executable and reproducible, provided there is an examiner's domain regarding the anatomy and proper technique. The values inferred in this study serve as a reference for veterinarians in the diagnosis of eye diseases.(AU)

Prevalencia de disfunción diastólica de acuerdo con las guías diagnósticas de 2009 y 2016. Relación con la valoración hemodinámica no invasiva / Prevalence of diastolic dysfunction (DD) according to the diagnostic guidelines of 2009 and 2016. Relationship with non-invasive hemodynamic assessment

Resumen Objetivos: Evaluar la prevalencia de DD de acuerdo con los criterios de las guías del 2009 y 2016, y su relación con la distensibilidad arterial sistémica (DAS) y la resistencia vascular periférica (RVP). Material y métodos: Se analizó a 306 pacientes ≥ 40 años de edad, con fracción de expulsión ≥ 50%. Se calcularon en todos DAS y RVP. Resultados: La prevalencia de DD fue de 32.7% y 22.9% según las guías de 2009 y 2016, respectivamente (p = < 0.0001). De acuerdo con las guías del 2009, los pacientes con DD presentaron una media de DAS menor que aquéllos con función normal (p = 0.0001), de modo similar a las guías del 2016 (p = 0.0007). La DD, según las guías de 2009 y 2016, mostró valores más altos de RVP que los normales (p = 0.005 y p = 0.018, respectivamente). Asimismo, la DD fue predictora, en el análisis univariado, de DAS < 0.60 ml.mm Hg-1 y RVP > 1,400 mmHg.min.l-1 según ambas guías. En el análisis multivariado, la DD, de acuerdo con las guías del 2009, persistió como predictor independiente de RVP > 1,400 mmHg.min.l-1. Conclusión: Las guías del 2016 reducen la prevalencia de DD. Ésta, tanto en las guías del 2009 como en las del 2106, fue predictor univariado de DAS < 0.60 ml.mmHg-1 y RVP > 1,400 mmHg.min.l-1. La DD, de acuerdo con las guías de 2009, resultó predictora independiente de RVP > 1,400 mmHg.min.l-1.

Abstract Objectives: To assess the prevalence of developmental disabilities (DD) according to the criteria of the 2009 and 2016 guidelines, and its association with systemic arterial compliance (DAS) and peripheral vascular resistance (RVP). Material and methods: 306 patients aged ≥ 40 years, with ejection fraction ≥ 50% were analyzed. It was estimated in all DAS and RVP. Results: The prevalence of DD was 32.7% and 22.9% according to the 2009 and 2016 guidelines, respectively (p ≤ 0.0001). Patients with DD according to the 2009 guideline had a lower average of DAS than those with normal function (p = 0.0001). Similar with the 2016 guide (p = 0.0007). The presence of DD according to the 2009 and 2016 guideline showed higher RVP values than normal values (p = 0.005 and p = 0.018, respectively). The DD according to both guidelines was a predictor, in the univariate analysis, of DAS < 0.60 ml.mmHg−1 and RVP > 1400 mmHg.min.l−1. The DD according to the 2009 guideline persisted as an independent predictor, in the multivariate analysis, of RVP > 1400 mmHg.min.l−1. Conclusion: The 2016 guide decreases the prevalence of DD. The DD, both from the 2009 and 2106 guidelines, were univariate predictors of DAS <0.60 ml.mmHg−1 and RVP > 1400 mmHg.min.l−1. The DD according to the 2009 guide, was an independent predictor of RVP > 1400 mmHg.min.l−1.

Valoración de ecuaciones derivadas del flujo pulmonar y regurgitación tricuspídea: utilidad en el test de vasoreactividad pulmonar / Valuation of equations derived from Pulmonary Flow and Tricuspid Regurgitation: usefulness in Pulmonary Vasoreactivity Testing

RESUMEN: Antecedentes: La presión media arterial pulmonar (PMAP) es una variable hemodinámica indispensable para el diagnóstico, clasificación y pronóstico de la Hipertensión Pulmonar (HP). Su cuantificación se realiza en forma invasiva por cateterismo cardíaco derecho (CCD) y no invasivamente por ecocardiografía Doppler. Masuyama propuso su medición mediante el gradiente transvalvular pulmonar diastólico derivado de la velocidad máxima inicial de la regurgitación pulmonar (∆RPi2) correspondiendo cercanamente a la medición invasiva. Objetivos: Revalidar 3 métodos ecocardiográficos que estiman la PMAP y valorar la utilidad del método de Chemla en el Test de Reactividad Vascular Pulmonar (TRVP). Métodos: Estudio prospectivo, observacional, doble ciego divido en dos etapas. A) o I) 30 pacientes se realizó ecocardiografía Doppler diagnóstica en nuestro centro. Se midieron regurgitación tricuspídea (RT) y tiempo de aceleración pulmonar (TAP) para derivar las siguientes ecuaciones: 1) 0.61xPSAP+1.95 (Chemla) 2) Gradiente presión media RT (∆PmRT) +PAD (presión-aurícula derecha) (Aduen) y 3) 79-0.45xTAP o 90-0.60xTAP, según sea el valor del TAP. B) o II) 10 pacientes enrolados para realizar el TRVP comparando la medición ecocardiográfica (Chemla) con CCD. Resultados: En la primera parte del estudio se encontró alta correlación entre las 3 ecuaciones: ChemlaAduen, R2=0.91; Chemla-Kitabatake, R2=0.87; Aduen-Kitabatake, R2=0,91. En la segunda parte comparando la PMAP-Chemla y Cateterismo derecho (CD) obtuvimos alta correlación: en tiempo 0, 30 min y recuperación:(R2=0.87, 0.99, 0.98, respectivamente). Ambas partes del estudio mostraron límites de concordancia satisfactoria con valor medio de la diferencia entre los métodos cercano a 1 en el t30 y tR del TRVP. Conclusión: los métodos dependientes de la medición de la RT son efectivos y confiables para estimar la PMAP. El método de Chemla es útil en el TRVP.

ABSTRACTS: Background: Mean Pulmonary arterial pressure (PMAP)is an indispensable hemodynamic variable for the diagnosis, classification and prognosis of Pulmonary Hypertension (PH). Its quantification is performed invasively by cardiac catheterization and non-invasively by Doppler echocardiography. Masuyama proposed its measurement by the transvalvular diastolic pulmonary gradient derived from the initial maximum velocity of pulmonary regurgitation(ΔPRi2) corresponding closely to the invasive measurement. Objectives: to compare 3 known echocardiographic methods to estimate MPAP and demonstrate the usefulness of the Chemla method in the Pulmonary Vascular Reactivity Test (PVRT). Methods: prospective, observational, double-blind study divided into two stages. A) 30 patients underwent diagnostic Doppler echocardiography. Tricuspid regurgitation (TR) and pulmonary acceleration time (PAT) were measured to derive the equations: 1) 0.61xSPAP + 1.95 (Chemla) 2) Gradient mean pressure TR (ΔPmTR) + RAP (right atrium pressure) (Aduen).3) 79-0.45xPAT o 90-0.60xPAT depending on the value of PAT. B) 10 patients enrolled to PVRT comparing the echocardiographic measurement (Chemla) with right catheterization. Results: in the first part of the study a high correlation between the 3 equations was found : ChemlaAduen, R2 = 0.91; Chemla-Kitabatake, R2=0.87; Aduen-Kitabatake, R2=0.91. In the second part comparing the MPAP-Chemla and RHC we obtained a high correlation in time 0, 30 min and recovery: (R2=0.87,0,99,0.98, respectively). Both parts of the study showed satisfactory limits concordance with mean value of the difference between the methods close to 1 in the t30 and tR of the TRVP. Conclusion: the methods dependent on the measurement of the TR are effective and reliable for estimating MPAP. The Chemla method is useful in the PVRT.

Comparison of the immediate hemodynamic changes induced by unilateral and bilateral spinal anesthesia in hypertensive elderly patients

BACKGROUND: The objective of this study was to compare the frequency of hypotension and immediate hemodynamic changes induced by unilateral and bilateral spinal anesthesia in hypertensive elderly patients. METHODS: Forty hypertensive elderly patients undergoing lower leg surgery were randomly allocated into unilateral (group US) and bilateral spinal anesthesia (group BS). After intrathecal bupivacaine injection, patients in group US were kept in the lateral position for 10 min while patients in group BS were immediately placed in the supine position. Hemodynamic parameters were measured for 20 min by non-invasive cardiac output monitor based on bioreactance. RESULTS: In both groups, mean arterial pressure was significantly decreased after spinal anesthesia compared to the baseline value. However, frequency of hypotension requiring vasoactive drug was significantly lower in group US (5%) than in group BS (35%) (P = 0.044). The dermatom of sensory block on the operated limb was significantly lower in group US [T10 (10–10)] than in group BS [T8 (7.5–10)] (P = 0.013). In comparison within the group, changes of cardiac index were similar as the baseline value in both groups, although total peripheral resistance index was constant in group US but significantly decreased in group BS. CONCLUSIONS: Unilateral spinal anesthesia effectively reduced the frequency of hypotension requiring vasoactive drug and affected hemodynamic performance less than bilateral spinal anesthesia.

Acute Hemodynamic Changes after Single Administration of Udenafil in Pulmonary Arterial Hypertension: a Phase IIa Study

BACKGROUND AND OBJECTIVES: Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single udenafil administration to determine the appropriate therapeutic dose. METHODS: Eighteen patients were randomly allocated into one of 3 groups: placebo, udenafil 50 mg (U50), and udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration. RESULTS: The mPAP significantly decreased in both the U50 and U100 (−11 mmHg and −8 mmHg from baseline, respectively, p < 0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=−8.5 mmHg and Δ=−14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events. CONCLUSIONS: This is the first demonstration of the acute hemodynamic changes induced by udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01553721.

Use of methylene blue in vasoplegic syndrome that developed during non-cardiac surgery: A case report

BACKGROUND: Vasoplegic syndrome is an increasingly recognized disease in perioperative medicine and is characterized by severe hypotension, normal or elevated cardiac output, and decreased systemic vascular resistance. It occurs commonly after cardiopulmonary bypass but may also occur after other types of surgery.CASE: Vasoplegic syndrome developed in our patient during posterior lumbar interbody fusion because of administering nicardipine after phenylephrine. However, the blood pressure did not increase as expected despite simultaneous use of norepinephrine and vasopressin to increase the reduced systemic vascular resistance.CONCLUSIONS: We present a case of vasoplegic syndrome that developed during posterior lumbar interbody fusion and was treated successfully with methylene blue.

Anxiety increases the blood pressure response during exercise

Aim: The hypothesis that higher levels of anxiety promote greater blood pressure (BP) responses during physical exercise is tested. The hypothesis that metaborreflex response is increased in an anxious individual is tested as well. Methods: There were 43 volunteers divided by anxiety level: 12 volunteers with mild, moderate and severe symptoms (anxious-group) and 31 volunteers with a minimum level of anxiety (control-group). Arterial BP, heart rate, and forearm blood flow were measured simultaneously during handgrip exercise and post-exercise ischemia, and forearm vascular resistance (FVR) was calculated. Results: Anxious group present higher systolic, diastolic and mean BP at rest when compared with control group (130±11 vs. 122±12 mmHg, p=0.048; 70±6 vs. 65±8 mmHg, p=0.033; 90±7 vs. 84±9 mmHg, p=0.033, respectively) and higher response of systolic, diastolic and mean BP and FVR during exercise when compared with control group (20±9 vs. 13±7 mmHg, p=0.009; 17±8 vs. 11±6 mmHg, p=0.006; 18±8 vs. 11±6 mmHg, p=0.005; and 0±13 vs. -7±9 units, p=0,003, respectively). During post-exercise ischemia, the anxious group also present higher response of diastolic BP, mean BP and FVR when compared with a control group (11±12 vs. 3±4 mmHg, p=0,001, 10±8 vs. 3±5 mmHg, p=0,002; 9±11 vs. -2± 8 units, p=0,03, respectively). Conclusion: Anxious individuals present higher BP responses during physical exercise when compared with those with minimal anxiety symptoms. This increased response may be explained, in part, by increased peripheral vascular resistance due to the greater metaborreflex response.(AU)

Uso de ecocardiografia junto ao leito para medir índices cardíaco e de resistência vascular sistêmica em pacientes pediátricos com choque séptico / The use of bedside echocardiography for measuring cardiac index and systemic vascular resistance in pediatric patients with septic shock

RESUMO Objetivo: Acompanhar o índice cardíaco e o índice de resistência vascular sistêmica até a ressuscitação. Métodos: Por meio de ecocardiografia junto ao leito, obteve-se um conjunto de parâmetros hemodinâmicos, inclusive débito cardíaco, volume sistólico, índice cardíaco, índice de resistência vascular sistêmica, integral velocidade-tempo, índice de desempenho miocárdico, tempo de reenchimento capilar e frequência cardíaca no momento zero após infusão de fluidos em bolo, e início e utilização de fármacos inotrópicos, com seguimento até 6 horas e 24 horas. Resultados: Incluíram-se 45 pacientes com choque séptico adquirido na comunidade. Os focos de infecção foram gastrenterite (24%), perfuração intestinal com necessidade de cirurgia emergencial (24%), pneumonia (20%), infecção do sistema nervoso central (22%) e infecção de tecidos moles (8%). Os isolados mais frequentes foram de Klebsiella e Enterobacter. Estimamos os fatores que afetaram o índice cardíaco: pressão venosa central elevada no momento zero (r = 0,33; p = 0,024) e persistência de frequência cardíaca elevada após 6 horas (r = 0,33; p = 0,03). O índice de resistência vascular sistêmica foi alto na maioria dos pacientes no momento zero e após 24 horas, e por ocasião da ressuscitação, afetando inversamente o índice cardíaco, assim como a integral velocidade-tempo (r = -0,416; -0,61; 0,55 e -0,295). O tempo de reenchimento capilar aumentado foi preditor clínico de valores baixos de integral velocidade-tempo após 24 horas (r = -0,4). O índice de mortalidade foi de 27%. Nos pacientes que não sobreviveram, observaram-se índices de resistência vascular sistêmica mais baixos e débitos cardíacos mais altos. Conclusão: O índice de resistência vascular sistêmica esteve persistentemente elevado em pacientes com choque frio, o que influenciou no índice de volume sistólico, no índice cardíaco e na integral velocidade-tempo. O uso de ecocardiografia para obtenção de mensurações hemodinâmicas é importante em pacientes pediátricos com choque séptico, para que se possam ajustar as doses de vasodilatadores e vasopressores, e obter os objetivos da ressuscitação em tempo apropriado.

ABSTRACT Objective: Follow-up of cardiac index and systemic vascular resistance index by bedside echocardiography until resuscitation. Methods: A set of hemodynamic parameters was obtained, including cardiac output, stroke volume, cardiac index, systemic vascular resistance index, velocity time integral, myocardial performance index, capillary refill time, and heart rate at 0 hours after fluid boluses before the start of inotropes, and followed up after 6 hours and 24 hours. Results: Included were 45 patients with community-acquired septic shock. Septic foci were gastroenteritis (24%), intestinal perforation requiring emergency surgery (24%), pneumonia (20%), central nervous system infection (22%) and soft tissue infection (8%). Klebsiella and Enterobacter were the most frequent isolates. We estimated the factors affecting the cardiac index: high central venous pressure at zero time (r = 0.33, p = 0.024) and persistently high heart rate at hour 6 (r = 0.33, p = 0.03). The systemic vascular resistance index was high in most patients at 0 and 24 hours and at the time of resuscitation and inversely affected the cardiac index as well as affecting the velocity time integral (r = -0.416, -0.61, 0.55 and -0.295). Prolonged capillary refill time was a clinical predictor of the low velocity time integral at 24 hours (r = -0.4). The mortality was 27%. Lower systemic vascular resistance index and higher cardiac output were observed in nonsurviving patients. Conclusion: There was a persistently high systemic vascular resistance index in cold shock patients that influenced the stroke volume index, cardiac index, and velocity time integral. The use of echocardiograms for hemodynamic measurements is important in pediatric septic shock patients to adjust dilators, and vasopressor doses and achieve resuscitation targets in a timely manner.

Comparison of Cardiac and Vascular Parameters in Powerlifters and Long-Distance Runners: Comparative Cross-Sectional Study / Comparação de Parâmetros Cardíacos e Vasculares em Powerlifters e Corredores de Longa Distância: Um Estudo Transversal Comparativo

Abstract Background: Cardiac remodeling is a specific response to exercise training and time exposure. We hypothesized that athletes engaging for long periods in high-intensity strength training show heart and/or vascular damage. Objective: To compare cardiac characteristics (structure and function) and vascular function (flow-mediated dilation [FMD] and peripheral vascular resistance [PVR]) in powerlifters and long-distance runners. Methods: We evaluated 40 high-performance athletes (powerlifters [PG], n = 16; runners [RG], n = 24) and assessed heart structure and function (echocardiography), systolic and diastolic blood pressure (SBP/DBP), FMD, PVR, maximum force (squat, bench press, and deadlift), and maximal oxygen uptake (spirometry). A Student's t Test for independent samples and Pearson's linear correlation were used (p < 0.05). Results: PG showed higher SBP/DBP (p < 0.001); greater interventricular septum thickness (p < 0.001), posterior wall thickness (p < 0.001) and LV mass (p < 0.001). After adjusting LV mass by body surface area (BSA), no difference was observed. As for diastolic function, LV diastolic volume, wave E, wave e', and E/e' ratio were similar for both groups. However, LA volume (p = 0.016) and BSA-adjusted LA volume were lower in PG (p < 0.001). Systolic function (end-systolic volume and ejection fraction), and FMD were similar in both groups. However, higher PVR in PG was observed (p = 0.014). We found a correlation between the main cardiovascular changes and total weight lifted in PG. Conclusions: Cardiovascular adaptations are dependent on training modality and the borderline structural cardiac changes are not accompanied by impaired function in powerlifters. However, a mild increase in blood pressure seems to be related to PVR rather than endothelial function.

Resumo Fundamento: Remodelamento cardíaco é uma resposta específica ao tempo e modalidade de treinamento. Nós hipotetizamos que atletas de treinamento de força de alta intensidade, por longo tempo, mostram dano à estrutura cardíaca e/ou vascular. Objetivo: Comparar as características cardíacas (estrutura e funcionalidade) e função vascular (dilatação fluxo-mediada, FMD e resistência vascular periférica, PVR) em powerlifters e corredores. Métodos: Nós avaliamos 40 atletas de alto-desempenho (powerlifters [PG], n = 16; corredores [RG], n = 24). Mensuramos estrutura e funcionalidade cardíaca (ecocardiografia), pressão arterial (SBP/DBP), FMD, PVR, força máxima (agachamento, supino e levantamento terra) e consumo máximo de oxigênio (ergoespirometria). Foi utilizado teste T de Student e correlação linear de Pearson (p < 0,05). Resultados: PG mostrou maior SBP/DBP (p < 0,001), espessura de septo interventricular (p < 0,001), parede posterior (p < 0,001) e massa do VE (p < 0,001); após ajuste pela superfície corporal (BSA), não houve diferença na massa do VE. O volume do VE, onda E, onda e', e a razão E/e' foram similares entre os grupos. O volume do AE (p = 0,016), mesmo ajustado pela BSA (p < 0,001) foi menor no PG. A função sistólica (volume sistólico final e fração de ejeção) e FMD foram similares nos grupos. Contudo, foi observada maior PVR no PG (p = 0,014). Houve uma correlação direta entre as alterações cardíacas e a carga total levantada no PG. Conclusões: As adaptações cardiovasculares são dependentes da modalidade e os valores encontrados na estrutura do coração não são acompanhados por prejuízo na funcionalidade. Entretanto, um leve aumento na pressão arterial pode estar associado com maior PVR e não com a função endotelial.

Lidocaine and pinacidil added to blood versus crystalloid cardioplegic solutions: study in isolated hearts

Abstract Objective: The present study aimed the functional recovery evaluation after long term of cardiac arrest induced by Custodiol (crystalloid-based) versus del Nido (blood-based) solutions, both added lidocaine and pinacidil as cardioplegic agents. Experiments were performed in isolated rat heart perfusion models. Methods: Male rat heart perfusions, according to Langendorff technique, were induced to cause 3 hours of cardiac arrest with a single dose. The hearts were assigned to one of the following three groups: (I) control; (II) Custodiol-LP; and (III) del Nido-LP. They were evaluated after ischemia throughout 90 minutes of reperfusion. Left ventricular contractility function was reported as percentage of recovery, expressed by developed pressure, maximum dP/dt, minimum dP/dt, and rate pressure product variables. In addition, coronary resistance and myocardial injury marker by alpha-fodrin degradation were also evaluated. Results: At 90 minutes of reperfusion, both solutions had superior left ventricular contractile recovery function than the control group. Del Nido-LP was superior to Custodiol-LP in maximum dP/dt (46%±8 vs. 67%±7, P<0.05) and minimum dP/dt (31%±4 vs. 51%±9, P<0.05) variables. Coronary resistance was lower in del Nido-LP group than in Custodiol-LP (395%±50 vs. 307%±13, P<0.05), as well as alpha-fodrin degradation, with lower levels in del Nido-LP group (P<0.05). Conclusion: Del Nido-LP cardioplegia showed higher functional recovery after 3 hours of ischemia. The analysis of alpha-fodrin degradation showed del Nido-LP solution provided greater protection against myocardial ischemia and reperfusion (IR) in this experimental model.

Exercise Training Attenuates Sympathetic Activity and Improves Morphometry of Splenic Arterioles in Spontaneously Hipertensive Rats / Treinamento Físico Atenua a Atividade Simpática e Melhora a Morfometria das Arteríolas Esplênicas em Ratos Espontaneamente Hipertensos

Abstract Background: Alterations in the structure of resistance vessels contribute to elevated systemic vascular resistance in hypertension and are linked to sympathetic hyperactivity and related lesions in target organs. Objective: To assess the effects of exercise training on hemodynamic and autonomic parameters, as well as splenic arteriolar damages in male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Methods: Normotensive sedentary (WKYS) and trained (WKYT) rats, and hypertensive sedentary (SHRS) and trained (SHRT) rats were included in this study. After 9 weeks of experimental protocol (swimming training or sedentary control), arterial pressure (AP) and heart rate (HR) were recorded in freely moving rats. We assessed the autonomic control of the heart by sympathetic and vagal autonomic blockade. Morphometric analyses of arterioles were performed in spleen tissues. The statistical significance level was set at p < 0.05. Results: Resting bradycardia was observed in both trained groups (WKYT: 328.0 ± 7.3 bpm; SHRT: 337.0 ± 5.2 bpm) compared with their respective sedentary groups (WKYS: 353.2 ± 8.5 bpm; SHRS: 412.1 ± 10.4 bpm; p < 0.001). Exercise training attenuated mean AP only in SHRT (125.9 ± 6.2 mmHg) vs. SHRS (182.5 ± 4.2 mmHg, p < 0.001). The WKYT showed a higher vagal effect (∆HR: 79.0 ± 2.3 bpm) compared with WKYS (∆HR: 67.4 ± 1.7 bpm; p < 0.05). Chronic exercise decreased sympathetic effects on SHRT (∆HR: -62.8 ± 2.8 bpm) in comparison with SHRS (∆HR: -99.8 ± 9.2 bpm; p = 0.005). The wall thickness of splenic arterioles in SHR was reduced by training (332.1 ± 16.0 µm2 in SHRT vs. 502.7 ± 36.3 µm2 in SHRS; p < 0.05). Conclusions: Exercise training attenuates sympathetic activity and AP in SHR, which may be contributing to the morphological improvement of the splenic arterioles.

Resumo Fundamento: Alterações na estrutura dos vasos de resistência contribuem para elevar a resistência vascular sistêmica na hipertensão, estando ligadas à hiperatividade simpática e lesões em órgãos-alvo. Objetivo: Avaliar os efeitos do treinamento físico nos parâmetros hemodinâmicos e autônomos, assim como as lesões arteriolares esplênica em ratos machos Wistar Kyoto (WKY) e espontaneamente hipertensos (SHR). Métodos: Ratos normotensos sedentários (WKYS) e treinados (WKYT), e ratos hipertensos sedentários (SHRS) e treinados (SHRT) foram incluídos neste estudo. Após nove semanas de aplicação do protocolo experimental (treinamento de natação ou controle sedentário), registraram-se a pressão arterial (PA) e a frequência cardíaca (FC) dos ratos em movimento livre. Avaliamos o controle autônomo do coração através de bloqueio autônomo simpático e vagal. Análises morfométricas das arteríolas esplênicas foram realizadas. Adotou-se o nível de significado estatístico de p < 0,05. Resultados: Observou-se bradicardia de repouso nos dois grupos treinados (WKYT: 328,0 ± 7,3 bpm; SHRT: 337,0 ± 5,2 bpm) em comparação aos seus respectivos grupos sedentários (WKYS: 353,2 ± 8,5 bpm; SHRS: 412,1 ± 10,4 bpm; p < 0,001). O treinamento físico atenuou a PA média apenas no grupo SHRT (125,9 ± 6,2 mmHg vs. 182,5 ± 4,2 mmHg no SHRS; p < 0,001). O grupo WKYT mostrou maior efeito vagal (∆FC: 79,0 ± 2,3 bpm) em comparação ao grupo WKYS (∆FC: 67,4 ± 1,7 bpm; p < 0,05). Exercício crônico diminuiu os efeitos simpáticos em SHRT (∆FC: -62.8 ± 2.8 bpm) em comparação a SHRS (∆FC: -99,8 ± 9,2 bpm; p = 0,005). A espessura da parede das arteríolas esplênicas nos SHR foi reduzida pelo treinamento (332,1 ± 16,0 µm2 nos SHRT vs. 502,7 ± 36,3 µm2 nos SHRS; p < 0,05). Conclusões: O treinamento físico atenua a atividade simpática e a PA em SHR, o que pode contribuir para melhorar a morfologia das arteríolas esplênicas.

Autonomic and Vascular Control in Prehypertensive Subjects with a Family History of Arterial Hypertension / Controle Autonômico e Vascular em Pré-Hipertensos com Histórico Familiar de Hipertensão Arterial

Abstract Background: Individuals with a family history of systemic arterial hypertension (FHSAH) and / or prehypertension have a higher risk of developing this pathology. Objective: To evaluate the autonomic and vascular functions of prehypertensive patients with FHSAH. Methods: Twenty-five young volunteers with FHSAH, 14 normotensive and 11 prehypertensive subjects were submitted to vascular function evaluation by forearm vascular conductance(VC) during resting and reactive hyperemia (Hokanson®) and cardiac and peripheral autonomic modulation, quantified, respectively, by spectral analysis of heart rate (ECG) and systolic blood pressure (SBP) (FinometerPRO®). The transfer function analysis was used to measure the gain and response time of baroreflex. The statistical significance adopted was p ≤ 0.05. Results: Pre-hypertensive individuals, in relation to normotensive individuals, have higher VC both at rest (3.48 ± 1.26 vs. 2.67 ± 0.72 units, p = 0.05) and peak reactive hyperemia (25, 02 ± 8.18 vs. 18.66 ± 6.07 units, p = 0.04). The indices of cardiac autonomic modulation were similar between the groups. However, in the peripheral autonomic modulation, greater variability was observed in prehypertensive patients compared to normotensive individuals (9.4 [4.9-12.7] vs. 18.3 [14.8-26.7] mmHg2; p < 0.01) and higher spectral components of very low (6.9 [2.0-11.1] vs. 13.5 [10.7-22.4] mmHg2, p = 0.01) and low frequencies (1.7 [1.0-3.0] vs. 3.0 [2.0-4.0] mmHg2, p = 0.04) of SBP. Additionally, we observed a lower gain of baroreflex control in prehypertensive patients compared to normotensive patients (12.16 ± 4.18 vs. 18.23 ± 7.11 ms/mmHg, p = 0.03), but similar delay time (-1.55 ± 0.66 vs. -1.58 ± 0.72 s, p = 0.90). Conclusion: Prehypertensive patients with FHSAH have autonomic dysfunction and increased vascular conductance when compared to normotensive patients with the same risk factor.

Resumo Fundamento: Indivíduos com histórico familiar de hipertensão arterial sistêmica (HFHAS) e/ou pré-hipertensão apresentam maior risco de desenvolver essa patologia. Objetivo: Avaliar as funções autonômica e vascular de pré-hipertensos com HFHAS. Métodos: Vinte e cinco voluntários jovens com HFHAS, sendo 14 normotensos e 11 pré-hipertensos foram submetidos à avaliação da função vascular, por meio da condutância vascular do antebraço (CV) durante repouso e hiperemia reativa (Hokanson®), e da modulação autonômica cardíaca e periférica, quantificada, respectivamente, por meio da análise espectral da frequência cardíaca (ECG) e da pressão arterial sistólica (PAS) (FinometerPRO®). A análise da função de transferência foi utilizada para mensurar o ganho e o tempo de resposta do barorreflexo. A significância estatística adotada foi p ≤ 0,05. Resultados: Pré-hipertensos, em relação aos normotensos, tem maior CV tanto em repouso (3,48 ± 1,26 vs. 2,67 ± 0,72 unidades; p = 0,05) quanto no pico hiperemia reativa (25,02 ± 8,18 vs. 18,66 ± 6,07 unidades; p = 0,04). Os índices da modulação autonômica cardíaca foram semelhantes entre os grupos. Entretanto, na modulação autonômica periférica, foi observado, nos pré-hipertensos em relação aos normotensos, maior variabilidade (9,4 [4,9-12,7] vs. 18,3 [14,8-26,7] mmHg2; p < 0,01) e maiores componentes espectrais de muito baixa (6,9 [2,0-11,1] vs. 13,5 [10,7-22,4] mmHg2; p = 0,01) e baixa frequências (1,7 [1,0-3,0] vs. 3,0 [2,0-4,0] mmHg2; p = 0,04) da PAS. Adicionalmente, observamos menor ganho do controle barorreflexo nos pré-hipertensos em relação aos normotensos (12,16 ± 4,18 vs. 18,23 ± 7,11 ms/mmHg; p = 0,03), porém, tempo de retardo semelhante (-1,55 ± 0,66 vs. -1,58 ± 0.72 s; p = 0,90). Conclusão: Pré-hipertensos com HFHAS tem disfunção autonômica e condutância vascular aumentada quando comparados a normotensos com o mesmo fator de risco.

Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system / 亚洲男科学杂志(英文版)

Testosterone deficiency is common in men with cardiovascular disease (CVD), and randomized placebo-controlled trials (RCTs) have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise (VO2max) and muscle strength in chronic heart failure (CHF), shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade (L-calcium channel) and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2maxand vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the insulin receptor, glucose transporters, and expression on regulatory enzymes of key metabolic pathways. The effect on high-density lipoprotein-cholesterol (HDL-C) differs between studies in that it has been found to fall, rise, or have no change in levels. Testosterone replacement can suppress the levels of circulating pro-inflammatory cytokines and stimulate the production of interleukin-10 (IL-10) which has anti-inflammatory and anti-atherogenic actions in men with CVD. No effect on C-reactive protein has been detected. No adverse effects on clotting factors have been detected. RCTs have not clearly demonstrated any significant evidence that testosterone improves or adversely affects the surrogate markers of atherosclerosis such as reduction in carotid intima thickness or coronary calcium deposition. Any effect of testosterone on prevention or amelioration of atherosclerosis is likely to occur over years as shown in statin therapy trials and not months as used in testosterone RCTs. The weight of evidence from long-term epidemiological studies supports a protective effect as evidenced by a reduction in major adverse CV events (MACEs) and mortality in studies which have treated men with testosterone deficiency. No RCT where testosterone has been replaced to the normal healthy range has reported a significant benefit or adverse effect on MACE nor has any recent meta-analysis.