Marcelo Custódio Rubira

Cardiovascular effects of partial sleep deprivation in healthy volunteers

Sleep deprivation is common in Western societies and is associated with increased cardiovascular morbidity and mortality in epidemiological studies. However, the effects of partial sleep deprivation on the cardiovascular system are poorly understood. In the present study, we evaluated 13 healthy male volunteers (age: 31 ± 2 yr) monitoring sleep diary and wrist actigraphy during their daily routine for 12 nights. The subjects were randomized and crossover to 5 nights of control sleep (>7 h) or 5 nights of partial sleep deprivation (<5 h), interposed by 2 nights of unrestricted sleep. At the end of control and partial sleep deprivation periods, heart rate variability (HRV), blood pressure variability (BPV), serum norepinephrine, and venous endothelial function (dorsal hand vein technique) were measured at rest in a supine position. The subjects slept 8.0 ± 0.5 and 4.5 ± 0.3 h during control and partial sleep deprivation periods, respectively (P < 0.01). Compared with control, sleep deprivation caused significant increase in sympathetic activity as evidenced by increase in percent low-frequency (50 ± 15 vs. 59 ± 8) and a decrease in percent high-frequency (50 ± 10 vs. 41 ± 8) components of HRV, increase in low-frequency band of BPV, and increase in serum norepinephrine (119 ± 46 vs. 162 ± 58 ng/ml), as well as a reduction in maximum endothelial dependent venodilatation (100 ± 22 vs. 41 ± 20%; P < 0.05 for all comparisons). In conclusion, 5 nights of partial sleep deprivation is sufficient to cause significant increase in sympathetic activity and venous endothelial dysfunction. These results may help to explain the association between short sleep and increased cardiovascular risk in epidemiological studies.

Ascorbic acid improves impaired venous and arterial endothelium-dependent dilation in smokers

AbstractAim:To compare the acute effects of ascorbic acid on vasodilation of veins and arteries in vivo.Methods:Twenty-six healthy non-smokers and 23 healthy moderate smokers were recruited in this study. The dorsal hand vein compliance technique and flow-mediated dilation were used. Dose-response curves to bradykinin and sodium nitroprusside were constructed to test the endothelium-dependent and -independent relaxation before and after acute infusion of ascorbic acid.Results:Smokers had an impaired venodilation with bradykinin compared with non-smokers (68.3%±13.2% vs 93.7%±20.1%, respectively; P<0.05). Ascorbic acid administration in the dorsal hand vein significantly increased the venodilation with bradykinin in smokers (68.3%± 13.2% vs 89.5%±6.3% before and after infusion, respectively; P<0.05) but not in non-smokers (93.7%±20.1% vs 86.4%±12.4% before and after infusion, respectively). Similarly, the arterial response in smokers had an impaired endothelium-dependent dilation compared with that in non-smokers (8.8%±2.7% vs 15.2%±2.3%, respectively; P<0.05) and ascorbic acid restored this response in smokers (8.8%±2.7% vs 18.7%±6.5% before and after infusion, respectively; P<0.05), but no difference was seen in non-smokers (15.2%±2.3% vs 14.0%±4.4% before and after infusion, respectively). The endothelium-independent dilation did not differ in both the groups studied. No important hemodynamic change was detected using the Portapress device.Conclusion:Smokers had impaired endothelium-dependent vasodilation responsiveness in both arterial and venous systems. Ascorbic acid restores this responsiveness in smokers.

Increased Sympathetic Nerve Activity Correlates With Neurovascular Compression at the Rostral Ventrolateral Medulla

We used microneurography to measure muscle sympathetic nerve activity (MSNA) in 25 hypertensive subjects and correlated these results with the presence or absence of signs of neurovascular compression (NVC) at the rostral ventrolateral (RVL) medulla on MRI. Subjects were divided into 3 groups based on MRI findings: NVC−, no MRI evidence of NVC (N=9); NVC+contact, image showing artery in contact but not compressing the RVL medulla (N=8); and NVC+compression, image showing arterial compression of the RVL medulla (N=8). The MSNA measurements were performed at rest, after a hypothermic stimulus, and during isometric exercise. The MSNA during rest in the NVC+compression group was significantly higher than that in the NVC+contact and NVC− groups (30.4±3.4 versus 17.5±1.1 and 21.4±3.2 spikes per minute, respectively). However, the blood pressure in the NVC+compression group was slightly but not significantly higher than that in the other 2 groups (183±7/115±8, 174±6/108±7, and 171±5/110±5 mm Hg, respectively). The increases in MSNA, blood pressure, and heart rate during the cold pressor and isometric exercise tests were similar. Our results show that, although resting MSNA is elevated in patients with true NVC of the RVL medulla, patients without NVC or with arterial contact but not overt compression of the RVL medulla have similar MSNA. These findings are important for identifying, among hypertensive patients with NVC, individuals who may have associated physiological repercussions, such as increased sympathetic activity.

Disfunção endotelial venosa em pacientes com doença de Chagas sem insuficiência cardíaca

ETODOSO grupo Chagas (G1) foi composto por quatorze mulheres e dois homens com idade de 46 ± 2,7 anos, e o grupo controle (G0), por sete mulheres e um homem, pareados em idade, peso, altura. A Tecnica de Complacencia da Veia Dorsal da Mao foi utilizada para avaliacao da funcao endotelial venosa. Foram infundidas doses crescentes de fenilefrina para se obter pre-constricao de 70% do basal; a seguir, foram administradas acetilcolina e nitroprussiato de sodio para avaliar as respostas de venodilatacao, respectivamente, dependentes e independentes do endotelio.

Effect of a low-dose oral contraceptive on venous endothelial function in healthy young women: preliminary results

BACKGROUND A possible increase in the incidence of venous thromboembolic events has been reported among users of third generation oral contraceptives. The objective of this study was to evaluate the effect of a low dose oral contraceptive (15 microg ethinyl estradiol/60 microg gestodene) on the venous endothelial function of healthy young women. METHODS Prospective case control study using the dorsal hand vein technique. Venous endothelial function was evaluated at baseline and after 4 months in the oral contraceptive users group (11 women) and in a control group (9 women). After preconstriction of the vein with phenylephrine, dose-response curves for acetylcholine and sodium nitroprusside were constructed. RESULTS In the contraceptive users group, a reduction occurred in the maximum venodilation response to acetylcholine and sodium nitroprusside after 4 months of oral contraceptive use, but this difference was not statistically significant (P > 0.05). No significant changes were detected in maximum venodilation responses to acetylcholine and sodium nitroprusside at the 4-month time point in the control group. CONCLUSION This study found no significant impairment of endothelium-dependent or independent venodilation in healthy young women following oral contraceptive use. Further studies are necessary using the same methodology in a larger sample over a longer follow-up period.

Androgenicity and venous endothelial function in post-menopausal women.

Background: Endothelial dysfunction is one of the early signs of cardiovascular damage. High androgen levels have been related to inflammatory endothelial markers in pre- and post-menopausal women. Aim: This cross-sectional study aimed at investigating whether free androgen index (FAI) [estimated by dividing total testosterone (nmol/l) by SHBG (nmol/l) × 100] is related to endothelial function during post-menopause. Subjects and methods: Twenty-six post-menopausal women were assessed with the dorsal hand vein compliance technique. Acetylcholine (Ach) and sodium nitroprusside (SNP) dose-response curves were constructed to test endothelium-dependent and independent relaxation, respectively. Results: Mean age was 54 yr (±4) and median time since menopause was 6 yr (interquartile range: 3–9). Patients were stratified according to FAI levels into two groups: FAI greater than or less than the group median of 2.5. Waist-to-hip ratio (WHR) was significantly higher in the group with FAI>2.5, as well as median dose of Ach for maximal vasodilation [720 (360–3600) ng/min with FAI>2.5 vs 36 (0.36–360) ng/min with FAI≤2.5; p=0.005]. Maximal vasodilation with SNP was similar in both groups. Positive correlations were observed between Ach doses and maximal vasodilation and FAI (r=0.473, p=0.015), waist (r=0.510, p= 0.011), and WHR (r=0.479, p=0.021). SHBG was negatively correlated with Ach doses (rs=−0.400, p=0.043). Conclusions: This study suggests that FAI, even within normal limits, is related to early changes in endothelial function in healthy post-menopausal women. Longitudinal studies are required to determine the clinical relevance of these findings.

Bradykinin or Acetylcholine as Vasodilators to Test Endothelial Venous Function in Healthy Subjects

INTRODUCTION The evaluation of endothelial function has been performed in the arterial bed, but recently evaluation within the venous system has also been explored. Endothelial function studies employ different drugs that act as endothelium-dependent vasodilatory response inductors. OBJECTIVES The aim of this study is to compare the endothelium-dependent venous vasodilator response mediated by either acetylcholine or bradykinin in healthy volunteers. METHODS AND RESULTS Changes in vein diameter after phenylephrine-induced venoconstriction were measured to compare venodilation induced by acetylcholine or bradykinin (linear variable differential transformer dorsal hand vein technique). We studied 23 healthy volunteers; 31% were male, and the subject had a mean age of 33 ± 8 years and a mean body mass index of 23 ± 2 kg/m2. The maximum endothelium-dependent venodilation was similar for both drugs (p = 0.13), as well as the mean responses for each dose of both drugs (r = 0.96). The maximum responses to acetylcholine and bradykinin also had good agreement. CONCLUSION There were no differences between acetylcholine and bradykinin as venodilators in this endothelial venous function investigation.

Venous endothelial dysfunction in patients with chronic heart failure

Venous Endothelial Dysfunction in Patients with Chronic Heart Failure Eneida R. Rabelo, Maria C. Irigoyen, Heitor Moreno, Fernanda C.C. Colombo, Marcelo Rubira, Karen R, Luis E. Rohde2—Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Servico de Cardiologia, Hospital de Clinicas de Porto Alegre, Brazil; Unidade de Hipertensao, Instituto do Coracao, Sao Paulo, Brazil; Faculdade de Enfermagem, Pontificia Universidade Catolica do Rio Grande do Sul, Brazil