Systemic vasoconstriction and mortality in patients with heart failure and reduced ejection fraction: A cohort of patients who underwent non-invasive hemodynamic monitoring.

Advanced heart failure primarily manifests during and after hospitalization for decompensation. Identifying prognostic factors is crucial for distinguishing patients who may benefit from drug therapy from those with end-stage disease. This study aimed to evaluate the prognostic significance of systemic vasoconstriction in patients with decompensated heart failure with a reduced ejection fraction. We evaluated patients hospitalized for decompensated heart failure with a left ventricular ejection fraction of < 40% who underwent non-invasive hemodynamic monitoring using the Modelflow method. The primary endpoint was all-cause mortality, and the data were analyzed using logistic regression. This study included 58 patients (71% men) with a mean age of 58.9 years, an ejection fraction of 23.4%, a median B-type natriuretic peptide of 1,005.0 pg/mL (interquartile range = 1,498.0), and 43% with Chagas disease. The cardiac index was 2.7 L∙min-1∙m-2, and the systemic vascular resistance index was 2,403.9 dyn∙s∙cm-5∙m-2. Over an average follow-up of 29.0 months, 51 (87.9%) patients died. Assessing three-year mortality, high systemic vascular resistance indices were predictive of events with a relative risk of 3.9 (95% confidence interval = 1.1-13.9; P-value = 0.037). In conclusion, non-invasive hemodynamic monitoring identifies systemic vasoconstriction, which is associated with poor prognosis in patients with advanced heart failure and reduced ejection fraction.

Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats.

BACKGROUND: Apigenin (4',5,7-trihydroxyflavone), a flavonoid with potential cardiovascular benefits, has unclear mechanisms of action. This study investigates its effects on vascular function in Spontaneously Hypertensive Rats (SHRs). METHODS: Mesenteric vascular beds (MVBs) were isolated from SHRs and perfused with increasing doses of apigenin after pre-contraction with phenylephrine. To explore the mechanisms, different MVBs were pre-perfused with antagonists and inhibitors, including indomethacin, L-NAME, and potassium channel blockers (tetraethylammonium, a non-specific potassium channel blocker; glibenclamide, an ATP-sensitive potassium channel blocker; 4-aminopyridine, a voltage-gated potassium channel blocker; charybdotoxin a selective intermediate-conductance calcium-activated potassium channel blocker; and apamin, a selective small-conductance calcium-activated potassium channel blocker). RESULTS: Apigenin induced a dose-dependent reduction in perfusion pressure in MVBs with intact endothelium, an effect abolished by endothelium removal. L-NAME reduced apigenin-induced vasodilation by approximately 40%. The vasodilatory effect was blocked by potassium chloride and tetraethylammonium. The inhibition of small and intermediate calcium-activated potassium channels with charybdotoxin and apamin reduced apigenin-induced vasodilation by 50%, and a combination of these blockers with L-NAME completely inhibited the effect. CONCLUSIONS: Apigenin promotes vasodilation in resistance arteries through endothelial nitric oxide and calcium-activated potassium channels. These findings suggest that apigenin could have therapeutic potential in cardiovascular disease, warranting further clinical research.

Low Caloric Intake Confers Cardiovascular Protection and Improves Functional Capacity Without Affecting Immunological Response in Sedentary Older Adults.

BACKGROUND: Aging is characterized by a decline in the cardiovascular hemodynamic response, which may be aggravated by undernutrition. However, no study has evaluated whether low caloric intake may affect cardiovascular hemodynamics and its possible relation with functional capacity and immune response in older adults. METHODS: Sixty-one older adults of both genders were enrolled in this study and were classified as normocaloric (n = 18) and hypocaloric (n = 43). All volunteers were evaluated for cardiovascular hemodynamics using impedance cardiography (PhysioFlow®); functional capacity by the 1' sit-to-stand test with SpO2 monitoring; whole-blood analysis using an automated hematocytometer (Sysmex®); and levels of IL-6, TNF-alpha, IL-10, and Klotho by ELISA. RESULTS: The hypocaloric group presented impaired functional capacity, measured by a reduced number of sit-to-stand repetitions (p < 0.0251) and impaired delta of SpO2 (p < 0.0307). In contrast, the hypocaloric group presented an improved stroke volume (p < 0.0352), systemic vascular resistance (p < 0.0075), and systemic vascular resistance index (p < 0.0184). In addition, no changes were observed in the whole-blood analysis (p > 0.05) or for IL-6 (p > 0.05), TNF-alpha (p < 0.05), IL-10 (p < 0.05), and Klotho (p > 0.05). CONCLUSIONS: A long-term hypocaloric diet in eutrophic older adults' resulted in an enhanced cardiovascular hemodynamic response but was associated with reduced functional capacity without changes in the immune response.

Prognostic value of angiographic microvascular resistance in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The Angiographic Microvascular Resistance (AMR), derived from a solitary angiographic view, has emerged as a viable substitute for the Index of Microcirculatory Resistance (IMR). However, the prognostic significance in ST-Segment Elevation Myocardial Infarction (STEMI) patients is yet to be established. This research endeavors to explore the prognostic capabilities of AMR in patients diagnosed with STEMI. METHODS: In this single-center, retrospective study, 232 patients diagnosed with STEMI who received primary Percutaneous Coronary Intervention (PCI) were recruited from January 1, 2018, to June 30, 2022. Utilizing the maximally selected log-rank statistics analysis, participants were divided into two cohorts according to an AMR threshold of 2.55 mmHg*s/cm. The endpoint evaluated was a composite of all-cause mortality or hospital readmission due to heart failure. RESULTS: At a median follow-up of 1.74 (1.07, 3.65) years, the composite endpoint event was observed in 28 patients within the higher AMR group and 8 patients within the lower AMR group. The higher AMR group showed a significantly higher risk for composite outcome compared to those within the low-AMR group (HRadj: 3.33; 95% CI 1.30‒8.52; p = 0.03). AMR ≥ 2.55 mmHg*s/cm was an independent predictor of the composite endpoint (HR = 2.33; 95% CI 1.04‒5.21; p = 0.04). Furthermore, a nomogram containing age, sex, left ventricle ejection fraction, post-PCI Quantitative Flow Ratio (QFR), and AMR was developed and indicated a poorer prognosis in the high-risk group for STEMI patients at 3 years. (HR=4.60; 95% CI 1.91‒11.07; p < 0.01). CONCLUSIONS: AMR measured after PCI can predict the risk of all-cause death or readmission for heart failure in patients with STEMI. AMR-involved nomograms improved predictive performance over variables alone.

Hyperaemia during dynamic handgrip exercise is preserved in healthy young subjects after recovery from COVID-19.

We sought to investigate possible impaired hyperaemia during dynamic handgrip exercise (HGE) in young healthy individuals who had recovered from COVID-19. We tested the vascular function in individuals recovered from COVID-19 using a nitric oxide donor (i.e., sodium nitroprusside; SNP), which could revert a possible impaired endothelial function during HGE. Further, we tested whether individuals who recovered from COVID-19 would present exaggerated brachial vascular resistance under an adrenergic agonist (i.e., phenylephrine; PHE) stimuli during HGE. Participants were distributed into two groups: healthy controls (Control; men: n = 6, 30 ± 3 years, 26 ± 1 kg/m2; and women: n = 5, 25 ± 1 years, 25 ± 1 kg/m2) and subjects recovered from COVID-19 (post-COVID; men: n = 6, 29 ± 3 years, 25 ± 1 kg/m2; and women: n = 10, 32 ± 4 years, 22 ± 1 kg/m2). Participants in the post-COVID group tested positive (RT-PCR) 12-14 weeks before the protocol. Heart rate (HR), brachial blood pressure (BP), brachial blood flow (BBF) and vascular conductance (BVC) at rest were not different between groups. The HGE increased HR (Control: Δ9 ± 0.4 bpm; and post-COVID: Δ11 ± 0.4 bpm) and BP (Control: Δ6 ± 1 mmHg; and post-COVID: Δ12 ± 0.6 mmHg) in both groups. Likewise, BBF (Control: Δ632 ± 38 ml/min; and post-COVID: Δ620 ± 27 ml/min) and BVC (Control: Δ6.6 ± 0.4 ml/min/mmHg; and post-COVID: Δ6.1 ± 0.3 ml/min/mmHg) increased during HGE. SNP did not change HGE-induced hyperaemia but did decrease BP, which induced a reflex-related increase in HR. PHE infusion also did not change the HGE-induced hyperaemia but raised BP and reduced HR. In conclusion, exercise-induced hyperaemia is preserved in healthy young subjects 12-14 weeks after recovery from COVID-19 infection.

Distinct Hemodynamic Responses That Culminate With Postural Orthostatic Tachycardia Syndrome.

It is of paramount importance to characterize the individual hemodynamic response of patients with postural orthostatic tachycardia syndrome (POTS) to select the best therapeutic intervention. Our aim in this study was to describe the hemodynamic changes in 40 patients with POTS during the head-up tilt test and compare them with 48 healthy patients. Hemodynamic parameters were obtained by cardiac bioimpedance. Patients were compared in supine position and after 5, 10, 15, and 20 minutes of orthostatic position. Patients with POTS demonstrated higher heart rate (74 beats per minute [64 to 80] vs 67 [62 to 72], p <0.001) and lower stroke volume (SV) (83.0 ml [72 to 94] vs 90 [79 to 112], p <0.001) at supine position. The response to orthostatic challenge was characterized by a decrease in SV index (SVI) in both groups (ΔSVI in ml/m2: -16 [-25 to -7.] vs -11 [-17 to -6.1], p = NS). Peripheral vascular resistance (PVR) was reduced only in POTS (ΔPVR in dyne.seg/cm5:-52 [-279 to 163] vs 326 [58 to 535], p <0.001). According to the best cut-off points obtained using the receiver operating characteristic analysis for the variation of SVI (-15.5%) and PVR index (PVRI) (-5.5%), we observed 4 distinct groups of POTS: 10% presented an increase in both SVI and PVRI after the orthostatic challenge, 35% presented a PVRI decrease with SVI maintenance or increase, 37.5% presented an SVI decrease with PVRI maintenance or elevation, and 17.5% presented a reduction in both variables. Body mass index, ΔSVI, and ΔPVRI were strongly correlated with POTS (area under the curve = 0.86 [95% confidence interval 0.77 to 0.92], p <0.0001). In conclusion, the use of appropriate cut-off points for hemodynamic parameters using bioimpedance cardiography during the head-up tilt test could be a useful strategy to identify the main mechanism involved and to select the best individual therapeutic strategy in POTS.

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.

Meta-Analysis of Pulmonary Artery Denervation for Treatment of Pulmonary Hypertension.

INTRODUCTION: Pulmonary artery denervation (PADN) can reduce the sympathetic nervous system (SNS) activity, reduce pulmonary artery pressure (PAP), and improve the quality of life in patients with pulmonary hypertension (PH). We conducted a systematic meta-analysis of the effectiveness of PADN in the treatment of PH patients. METHODS: This is a comprehensive literature search including all public clinical trials investigating the effects of PADN on PH. Outcomes were mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), right ventricular (RV) Tei index, 6-minute walk distance (6MWD), and New York Heart Association (NYHA) cardiac function grading. RESULTS: A total of eight clinical studies with 213 PH patients who underwent PADN were included. Meta-analysis showed that after PADN, mPAP (mean difference [] -12.51, 95% confidence interval [CI] -17.74 to -7.27, P<0.00001) (mmHg) and PVR ( -5.17, 95% CI -7.70 to -2.65, P<0.0001) (Wood unit) decreased significantly, CO ( 0.59, 95% CI 0.32 to 0.86, P<0.0001) (L/min) and 6MWD ( 107.75, 95% CI 65.64 to 149.86, P<0.00001) (meter) increased significantly, and RV Tei index ( -0.05, 95% CI -0.28 to 0.17, P=0.63) did not change significantly. Also after PADN, the proportion of NYHA cardiac function grading (risk ratio 0.23, 95% CI 0.14 to 0.37, P<0.00001) III and IV decreased significantly. CONCLUSION: This meta-analysis supports PADN as a potential new treatment for PH. Further high-quality randomized controlled studies are needed.

Changes of operative performance of pulse pressure variation as a predictor of fluid responsiveness in endotoxin shock.

Several limitations regarding pulse pressure variation (PPV) use have been reported. Our aim was to describe changes in the PPV operative performance as a predictor of fluid responsiveness during the development of a swine endotoxin shock model and to assess hemodynamic variables associated with PPV changes. A swine porcine endotoxin shock model was established (Escherichia Coli 055:B5 endotoxin) in 7 pigs, and 3 pigs were included in the control group. The endotoxin was infused until the mean arterial pressure (MAP) dropped below 50 mmHg (TH0); then, the model animal was reanimated with fluids and vasopressors. We performed fluid challenges every hour for 6 h. ROC curve analysis and a linear mixed model were performed. The area under the curve of PPV decreased from 0.95 (0.81-1.00) to 0.60 (0.17-1.00) at TH0. Its cutoff increased from 10.5 to 22.00% at TH0. PPV showed an inverse relationship with stroke volume, mean systemic filling pressure, MAP, and systemic vascular resistance (SVR) (p < 0.001, AIC = 111.85). The PPV operative performance as a predictor of fluid responsiveness decreased with the progression of shock. This could lead to an inverse association between PPV and the following variables: MAP and SVR.

Etiopathogenic features of severe epistaxis in histological samples from individuals with or without arterial hypertension.

There is a consensus that arterial hypertension (AH) is associated with stroke. Therefore, this study aimed to evaluate the histology of the microvasculature associated with the mucosa of the posterior nasal cavity to identify possible factors related to vascular weakening and rupture. Histological sections were obtained from hypertensive and normotensive individuals, regardless of epistaxis. Our results showed that the group with AH had: (a) smaller median diameter of the lumen of arteries and arterioles; (b) increased thickness of the intimal arteries and arterioles, slight inflammatory infiltrate, and rupture of internal elastic lamina; (c) greater thickness of the middle tunica in arterioles; (d) lower percentage of histological sections with non-injured intimal layers in capillaries, arterioles, and small arteries; (e) lower percentage of histological sections with intact media tunic and/or myocytes juxtaposed in arteries and arterioles; (f) no difference between the diameters of small arteries or arterioles. The intima was thicker in individuals with severe epistaxis than in the normotensive group, but it did not differ from the AH group. Thus, hypertension may cause structural lesions in the vascular layers, and in the absence of tissue repair and the persistence of AH, these lesions may favour vascular rupture, especially during hypertensive peaks.

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.

Hemodynamic phenotyping of transgenic rats with ubiquitous expression of an angiotensin-(1-7)-producing fusion protein.

Activation of the angiotensin (Ang)-converting enzyme (ACE) 2/Ang-(1-7)/MAS receptor pathway of the renin-angiotensin system (RAS) induces protective mechanisms in different diseases. Herein, we describe the cardiovascular phenotype of a new transgenic rat line (TG7371) that expresses an Ang-(1-7)-producing fusion protein. The transgene-specific mRNA and the corresponding protein were shown to be present in all evaluated tissues of TG7371 with the highest expression in aorta and brain. Plasma Ang-(1-7) levels, measured by radioimmunoassay (RIA) were similar to control Sprague-Dawley (SD) rats, however high Ang-(1-7) levels were found in the hypothalamus. TG7371 showed lower baseline mean arterial pressure (MAP), assessed in conscious or anesthetized rats by telemetry or short-term recordings, associated with increased plasma atrial natriuretic peptide (ANP) and higher urinary sodium concentration. Moreover, evaluation of regional blood flow and hemodynamic parameters with fluorescent microspheres showed a significant increase in blood flow in different tissues (kidneys, mesentery, muscle, spleen, brown fat, heart and skin), with a resulting decrease in total peripheral resistance (TPR). TG7371 rats, on the other hand, also presented increased cardiac and global sympathetic tone, increased plasma vasopressin (AVP) levels and decreased free water clearance. Altogether, our data show that expression of an Ang-(1-7)-producing fusion protein induced a hypotensive phenotype due to widespread vasodilation and consequent fall in peripheral resistance. This phenotype was associated with an increase in ANP together with an increase in AVP and sympathetic drive, which did not fully compensate the lower blood pressure (BP). Here we present the hemodynamic impact of long-term increase in tissue expression of an Ang-(1-7)-fusion protein and provide a new tool to investigate this peptide in different pathophysiological conditions.

Redox Switches Controlling Nitric Oxide Signaling in the Resistance Vasculature and Implications for Blood Pressure Regulation: Mid-Career Award for Research Excellence 2020.

The arterial resistance vasculature modulates blood pressure and flow to match oxygen delivery to tissue metabolic demand. As such, resistance arteries and arterioles have evolved a series of highly orchestrated cell-cell communication mechanisms between endothelial cells and vascular smooth muscle cells to regulate vascular tone. In response to neurohormonal agonists, release of several intracellular molecules, including nitric oxide, evokes changes in vascular tone. We and others have uncovered novel redox switches in the walls of resistance arteries that govern nitric oxide compartmentalization and diffusion. In this review, we discuss our current understanding of redox switches controlling nitric oxide signaling in endothelial and vascular smooth muscle cells, focusing on new mechanistic insights, physiological and pathophysiological implications, and advances in therapeutic strategies for hypertension and other diseases.

Pulmonary hypertension in systemic sclerosis: diagnosis by systematic screening and prognosis after three years follow-up.

BACKGROUND: Systemic sclerosis (SSc) is a rare disease, and the presence of pulmonary hypertension can be a determining factor in prognosis. The aim of this study was to evaluate the diagnosis, profile, and prognosis of systemic sclerosis pulmonary hypertension (SSc-PH) diagnosed by systematic screening in a Brazilian population. METHODS: A cohort of SSc patients underwent systematic screening for SSc-PH. Patients were referred for right heart catheterization (RHC) according to transthoracic echocardiogram or a combination of diagnostic tools. The clinical, immunological, and hemodynamic features and prognosis after 3 years were evaluated. RESULTS: Twenty patients underwent RHC. SSc pulmonary arterial hypertension (SSc-PAH) was the most common group of SSc-PH. These patients had long disease duration, high urate levels and highly elevated mean pulmonary arterial pressure (mPAP) and peripheral vascular resistance (PVR) on hemodynamics. Patients with mPAP > 20- < 25 mmHg had hemodynamic features of intermediate disease. Patients with SSc-PH associated to interstitial lung disease (SSc-ILD-PH) had signs of vasculopathy on hemodynamics. In patients with no-SSc-PH, the survival at 1, 2, and 3 years was 96%, 92% and 92%, respectively and in patients with SSc-PH it was 86.7%, 60% and 53.3%, respectively. CONCLUSIONS: Patients identified with SSc-PAH and SSc-ILD-PH in our screening had severe clinical and hemodynamic features. Mortality remains high in SSc-PH but was more related to Bo-PAH and SSc-ILD-PH, while in SSc-PAH, the prognosis was better. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 72968188, July 8th, 2021. Retrospectively registered.

Testicular shape, scrotal skin thickness and testicular artery blood flow changes in bulls of different ages.

The aim of this study was to compare the biometric testicular characteristics, skin thickness and haemodynamics of the testicular artery of 12- and 24-month-old bulls using Doppler ultrasonography, the study was conducted using 48 indicus-taurus animals. The scrotal circumference (SC) and biometry characteristics of the bulls were measured to calculate the testicular volume. Doppler ultrasonography was used to obtain the haemodynamic values of the testicular artery. The skin thickness and volume were lower (p<.01) in the younger bulls (12 months:4.68 ± 0.68 mm; 168.76 ± 47.96 cm3 ) versus 24 months (5.05 ± 0.89; 499.73 ± 129.24 cm3 ) animals (p<.01). During diastole, mean velocity was lower in the 12 months (7.98 ± 3.83) than in the 24 months (11.37 ± 4.15) animals (p <.05). The 12-month-old animals had higher pulsatility and resistivity indices (0.49 ± 0.02; 0.51 ± 0.20) compared to the 24-month-old animals (0.32 ± 0.16; 0.40 ± 0.15) (p < .05). The final testicular end velocity was lower in animals with long/moderate-shaped (L/M) (7.31 ± 2.91) than in those moderate/oval-shaped (M/O) (11.48 ± 3.88) testicles (p < .05). Animals with L/M testes presented higher pulsatility values and resistivity indices (0.51 ± 0.05; 0.55 ± 0.04) compared to animals with M/O shape (0.29 ± 0.20; 0.36 ± 0.15). We showed that the blood flow of the supra testicular artery between the two evaluated ages differed, and that 24-month-old bulls presented better thermoregulation capacity. Animals with a long/moderate testicular format presented a greater vascular resistance, which was imposed on the blood flow due to the anatomical differences in the testicular artery, resulting in lower velocity, and indicating better heat dissipation in this format.

Normative Echocardiographic Values for Right and Left Ventricular Function in Extremely Premature Neonates.

OBJECTIVE: To identify the measures of biventricular function and surrogates of pulmonary vascular resistance that can be expected in relatively stable extremely premature neonates, and evaluate maturational changes in myocardial performance in this patient population. STUDY DESIGN: This was a prospective observational study. Clinically stable extremely preterm newborns were divided into 3 cohorts based on gestational age: cohort 1 (240/7-256/7 weeks), cohort 2 (260/7-276/7 weeks), and cohort 3 (280/7-296/7 weeks). Serial echocardiograms were obtained on day of life 3-5, 7-10, and just prior to discharge. RESULTS: In total, 46 subjects met the criteria aimed at capturing only the most clinically healthy and stable newborns less than 296/7 weeks of gestational age. Myocardial performance was reliably assessed by echocardiography with high inter-reader correlation. Normative values were identified for right ventricular function, left ventricular function, and surrogates of pulmonary vascular resistance. CONCLUSIONS: Biventricular systolic performance is significantly different in the clinically stable extremely premature neonate when compared with healthy full-term newborns. All participants had evidence of poor biventricular compliance at birth which improved with maturation. Extreme prematurity does not appear to adversely affect myocardial functional maturation at the time of term corrected age and/or discharge.

Time-Dependent Effects of Individual and Combined Treatments With Nebivolol, Lisinopril, and Valsartan on Blood Pressure and Vascular Reactivity to Angiotensin II and Norepinephrine.

Clinical guidelines suggest the combination of 2 drugs as a strategy to treat hypertension. However, some antihypertensive combinations have been shown to be ineffective. Therefore, it is necessary to determine whether differences exist between the results of monotherapy and combination therapy by temporal monitoring of the responses to angiotensin II and norepinephrine, which are vasoconstrictors involved in the development of hypertension. Thus, the purpose of this work was to determine the vascular reactivity to angiotensin II and norepinephrine in spontaneously hypertensive rat (SHR) aortic rings after treatment with valsartan, lisinopril, nebivolol, nebivolol-lisinopril, and nebivolol-valsartan for different periods of time. In this study, male SHR and Wistar Kyoto normotensive (WKY) rats were divided into 7 groups treated for 1, 2, and 4 weeks: (1) WKY + vehicle, (2) SHR + vehicle; (3) SHR + nebivolol; (4) SHR + lisinopril; (5) SHR + valsartan; (6) SHR + nebivolol-lisinopril; and (7) SHR + nebivolol-valsartan. Blood pressure was measured by the tail-cuff method, and vascular reactivity was determined from the concentration-response curve to angiotensin II and norepinephrine in aortic rings. The results showed that the combined and individual treatments reduced mean blood pressure at all times evaluated. All treatments decreased vascular reactivity to angiotensin II; however, in the case of lisinopril and nebivolol-lisinopril, the effect observed was significant up to 2 weeks. All treatments decreased the reactivity to norepinephrine up to week 4. These results show a time-dependent difference in vascular reactivity between the pharmacological treatments, with nebivolol-valsartan and nebivolol-lisinopril being both effective combinations. Additionally, the results suggest crosstalk between the renin-angiotensin and sympathetic nervous systems to reduce blood pressure and to improve treatment efficacy.

Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation.

Deletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca2+]i of endothelial cells. Changes in NO-mediated vasodilation, membrane potential, superoxide anion (O2 ·-) formation, and endothelial cell [Ca2+]i were analyzed in rat isolated mesenteric arterial beds and primary cultures of mesenteric endothelial cells. Inhibition of Panx-1 channels with probenecid (1 mM) or the Panx-1 blocking peptide 10Panx (60 µM) evoked an increase in the ACh (100 nM)-induced vasodilation of KCl-contracted mesenteries and in the phosphorylation level of endothelial NO synthase (eNOS) at serine 1177 (P-eNOSS1177) and Akt at serine 473 (P-AktS473). In addition, probenecid or 10Panx application activated a rapid, tetrodotoxin (TTX, 300 nM)-sensitive, membrane potential depolarization and [Ca2+]i increase in endothelial cells. Interestingly, the endothelial cell depolarization was converted into a transient spike after removing Ca2+ ions from the buffer solution and in the presence of 100 µM mibefradil or 10 µM Ni2+. As expected, Ni2+ also abolished the increment in [Ca2+]i. Expression of Nav1.2, Nav1.6, and Cav3.2 isoforms of voltage-dependent Na+ and Ca2+ channels was confirmed by immunocytochemistry. Furthermore, the Panx-1 channel blockade was associated with an increase in O2 ·- production. Treatment with 10 µM TEMPOL or 100 µM apocynin prevented the increase in O2 ·- formation, ACh-induced vasodilation, P-eNOSS1177, and P-AktS473 observed in response to Panx-1 inhibition. These findings indicate that the Panx-1 channel blockade triggers a novel complex signaling pathway initiated by the sequential activation of TTX-sensitive Nav channels and Cav3.2 channels, leading to an increase in NO-mediated vasodilation through a NADPH oxidase-dependent P-eNOSS1177, which suggests that Panx-1 may be involved in the endothelium-dependent control of arterial blood pressure.