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% 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%), 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%. 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

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

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%. 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

Does Resistance Training with Blood Flow Restriction Affect Blood Pressure and Cardiac Autonomic Modulation in Older Adults?

International Journal of Exercise Science 14(3): 410-422, 2021. Resistance training (RT) with blood flow restriction (BFR) appears to accelerate muscle hypertrophy and strength gains in older populations. However, the training-related effects of RT with BFR upon blood pressure (BP) and cardiac autonomic modulation in the elderly remains unclear. The objective of this study is to compare the chronic effects of low-intensity RT performed with soft BFR (BFR) vs. high-intensity (HI) and low-intensity RT (CON) without BFR on BP and heart rate variability (HRV) indices in older adults. Thirty-two physically inactive participants (72 ± 7 yrs) performed RT for upper and lower limbs (50-min sessions, 3 times/week) for 12 weeks, being assigned into three groups: a) BFR; 30% of 1 repetition maximum (RM) with BFR corresponding to 50% of arterial occlusion pressure; b) HI; 70% of 1RM without BFR; c) CON; 30% of 1 RM without BFR. Resting BP and HRV were assessed at rest in the supine position, before and after exercise interventions. Systolic BP (Δ = -7.9 ± 8.0 mmHg; p = 0.002; effect size = 0.62), diastolic BP (Δ = -5.0 ± 6.0 mmHg; p = 0.007; effect size = 0.67) and mean arterial pressure (Δ = -6.3 ± 6.5 mmHg; p = 0.003/effect size = 0.77) reduced after BFR, remaining unaltered in HI and CON. HRV indices of sympathetic and vagal modulation did not change in all groups (p ≥ 0.07 for all comparisons). 12-wk RT with low intensity and relatively soft BFR substantially reduced BP at rest in older adults vs. traditional RT performed with either low or high intensity. Those reductions were not parallel to changes in autonomic modulation

Acute effects of exercise with blood flow restriction on endothelial function in healthy young and older populations: a systematic review

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 &gt; 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 &ge; 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.</

Acute effects of physical exercise with different levels of blood flow restriction on vascular reactivity and biomarkers of muscle hypertrophy, endothelial function and oxidative stress in young and elderly subjects – A randomized controlled protocol

Background: Gains in muscle mass and strength have been documented in exercise training with blood flow restriction (BFR). However, the impact of retrograde blood flow during BFR training on vascular health remains unclear. The present study designed a protocol to evaluate the acute effects of exercise performed with different levels of BFR on vascular reactivity and biomarkers of endothelial function, oxidative stress, and muscle hypertrophy in young and older individuals. Methods and study design: Sixty-eight physically inactive eutrophic men [34 young (18–25-yrs old) and 34 elderly (≥65-yrs old)] will be included in the study. Subjects will undergo three experimental protocols: a) control (ExCON) – handgrip exercise with intensity of 30% of the maximum voluntary contraction (MVC); b) blood flow restriction (ExBFR) – handgrip exercise with a resistance of 30% of the MVC with low level of BFR [80% of arterial occlusion pressure at rest (rAOP)]; and c) arterial occlusion pressure (ExAOP) – handgrip exercise with a resistance of 30% of the MVC with high level of BFR (120% of rAOP). Primary outcomes will be: a) vascular reactivity assessed by venous occlusion plethysmography; b) endothelial function (nitric oxide and apoptotic endothelial micro particles; c) oxidative stress (thiobarbituric acid reactive substances). Growth hormone and lactate concentration will be measured as secondary outcomes reflecting the hypertrophic drive and metabolic stress, respectively. Discussion: The findings of the present study may help to elucidate the age-related impacts of BFR training on the vascular health

Increment of body mass index is positively correlated with worsening of endothelium-dependent and independent changes in forearm blood flow

Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. We have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls, Overweight, Obese class I, Obese class II, and Obese class III. Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Our data suggests that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow