Acute effects of exercise with blood flow restriction on endothelial function in healthy young and older populations: a systematic review / Efeitos agudos do exercício com restrição do fluxo sanguíneo na função endotelial de jovens e idosos saudáveis: uma revisão sistemática

The objective of this review is to identify the acute effects of blood flow restriction (BFR) with vs without exercise on endothelial function in healthy individuals and the changes in endothelial function in young and older adults following different levels of exclusive BFR vs free flow. Systematic searches were performed in the following databases: PubMed, Web of Science, Scopus, and Cochrane Library, from inception to July 17, 2021. The studies included healthy individuals who underwent assessments of endothelial function before and after experimental protocols through endothelium-dependent flow-mediated dilatation. In total, 4890 studies were screened, and 6 studies of moderate-to-high methodological quality (Physiotherapy Evidence Database scores 6 ­ 10) including 82 subjects (aged 24 ­ 68 years) were eligible. Overall, flow-mediated dilatation increased in the non-cuffed arm immediately and 15 minutes after exercise, with no change in the cuffed arm (BFR of 60 ­ 80 mmHg). In protocols without exercise, cuff pressures of 25 ­ 30 mmHg applied for 30 minutes did not promote changes in the endothelial function, while those > 50 mmHg induced a dose-dependent attenuation of flow-mediated dilatation only in young individuals. A moderate level of BFR appears to have no effect on endothelial function after acute exercise. In non-exercise conditions, reductions in flow-mediated dilatation seem to result from increased retrograde shear provoked by cuff pressures ≥ 50 mmHg in young but not in older adults. An exercise-related increase in antegrade shear rate leads to a greater nitric oxide-mediated vasodilator response. However, BFR appears to attenuate this effect in young but not in older individuals. (AU)

O objetivo desta revisão foi identificar os efeitos agudos da restrição do fluxo sanguíneo (RFS) com vs. sem exercício na função endotelial de indivíduos saudáveis, bem como as alterações na função endotelial em jovens e idosos após diferentes níveis de RFS vs. fluxo livre. Pesquisas sistemáticas foram realizadas nas bases United States National Library of Medicine (PubMed), Web of Science, Scopus e Cochrane Library até 17 de julho de 2021. Os estudos incluíram indivíduos saudáveis que avaliaram a função endotelial antes e após protocolos experimentais, por meio da dilatação mediada por fluxo. Foi selecionado o total de 4.890 estudos, e foram elegíveis seis de moderada a alta qualidade metodológica (Physioterapy Evidence Database 6 ­ 10 pontos), incluindo 82 indivíduos (24 ­ 68 anos). No geral, a dilatação mediada por fluxo aumentou no braço sem manguito, imediatamente e 15 minutos após o exercício, sem alteração no braço com manguito (RFS de 60 ­ 80 mmHg). Em protocolos sem exercício, pressões do manguito de 25 ­ 30 mmHg aplicadas por 30 minutos não promoveram alterações na função endotelial, enquanto aquelas > 50 mmHg induziram uma atenuação dose-dependente da dilatação mediada por fluxo em indivíduos jovens. Um nível moderado de RFS parece não ter efeito na função endotelial após uma sessão de exercício. Em condições sem exercício, as reduções na dilatação mediada por fluxo parecem resultar do aumento do cisalhamento retrógrado provocado por pressões do manguito ≥ 50 mmHg em jovens, mas não em idosos. O aumento da taxa de cisalhamento anterógrado relacionada ao exercício leva a maior resposta vasodilatadora mediada pelo óxido nítrico. No entanto, a RFS parece atenuar esse efeito em jovens, mas não em . (AU)

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

OBJECTIVE: Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion. METHOD: Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW= 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch. RESULTS: Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia. CONCLUSION: Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamineinduced macromolecular permeability.

Metabolic disturbances linked to obesity: the role of impaired tissue perfusion / Alterações metabólicas associadas à obesidade: o papel da disfunção da microcirculação tecidual

Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 µm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and rennin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.

Associada ao aumento do risco de eventos cardiovasculares e ao câncer, a obesidade é um problema mundial, que atinge tanto países desenvolvidos quanto em desenvolvimento. A microcirculação é composta por arteríolas, capilares e vênulas (diâmetro interno médio < 100 µm) e é o local onde ocorrem a oferta de nutrientes e as trocas entre o tecido e o sangue. A disfunção microcirculatória é um evento precoce na obesidade e este pode ser secundário à disfunção endotelial ou à redução no número de capilares (rarefação capilar). Novas técnicas em pesquisa permitem a avaliação da microcirculação em diferentes leitos vasculares em humanos. Estudos sugerem uma correlação entre disfunção endotelial e obesidade visceral. Acredita-se que o estresse oxidativo, a inflamação e a atividade aumentada do sistema renina-angiotensina estão entre os fatores envolvidos nessa associação. O comprometimento microcirculatório presente na obesidade sugere que esse pode ser um fator causal importante nas desordens relacionadas com a obesidade, como resistência insulínica e hipertensão.

Effects of buflomedil and pentoxifylline on hamster skin-flap microcirculation: prediction of flap viability using orthogonal polarization spectral imaging

OBJECTIVE: This study investigated the effects of buflomedil and pentoxifylline, both of which are used in reconstructive surgery of hamster skin flap microcirculation, and evaluated the skin flap survival rate by orthogonal polarization spectral imaging. METHOD: Twenty-four adult male Syrian golden hamsters were divided into three groups: a control (C, 0.1 ml 0.9 percent saline), buflomedil (B, 3 mg/kg/day), and pentoxifylline group (P, 14.5 mg/kg/day). Treatments administered intraperitoneally were initiated 1 hour before skin flap preparation and continued for 7 days post-operatively at 12-hour intervals. Preparations (skin flaps) were divided into 12 fields, which were organized into six bands. Functional capillary density (FCD, in mm/mm²), distance from the skin flap base to blood flow cessation (Dist with flow, in cm), percentage of viable skin (VA, in percent), and qualitative analysis of blood flow by orthogonal polarization spectral imaging were performed at 1 and 24 hours and on the seventh post-operative day. RESULT: Bands IV, V, and VI presented no flow independent of time. The functional capillary density group B was higher than that of groups C and P, primarily after 24 hours. All groups showed an increase in D with time but reached similar final distances (C = 2.73, B = 2.78 and P = 2.70 cm). Moreover, the percentage of viable areas remained at approximately 50 percent. The orthogonal polarization spectral imaging was useful to assess viability by counting fields with and without blood flow. CONCLUSIONS: Functional capillary density values were higher in the buflomedil group compared to the control and pentoxifylline groups in this model. Functional capillary density did not influence D or the percentage of VA, and the technique showed favorable potential to assess/predict the viability of skin flaps within 1 h after surgery.

Treatment of essential hypertension does not normalize capillary rarefaction

OBJECTIVES: To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS: We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS: Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1±1.4 vs. 33.9±1.9 cap/mm², p<0.01), during post-occlusive reactive hyperemia (29.3±1.9 vs. 38.2±2.2 cap/mm², p<0.01) and during venous congestion responses (31.4±1.9 vs. 41.1±2.3 cap/mm², p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1 percent. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98±0.05 vs. 1.17±0.04 mm/s, p<0.05). CONCLUSIONS: Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension.