Postocclusive Reactive Hyperemia Response Research Articles

Effects of sensory nerve blockade on cutaneous microvascular responses to ischemia-reperfusion injury.

Examine the effects of sensory nerve blockade on cutaneous post-occlusive reactive hyperemia (PORH) and local thermal hyperemia (LTH) following prolonged upper limb ischemia. In nine males [28years (standard deviation:6)], volar forearm skin blood flux normalized to maximum vasodilation (%SkBFmax) was assessed at control (CTRL) and sensory nerve blockade (EMLA) treated sites during the PORH response following 20-min of complete arm ischemia and during rapid LTH (33-42°C, 1°C·20s-1, held for ~30-min+20-min at 44°C) before and after ischemia-reperfusion (IR) injury. EMLA increased mean [95% confidence-interval] PORH amplitude by 21%SkBFmax ([9,33]; p=0.003), delayed time to peak by 111s ([40,182]; p=0.007) and increased area under the curve by 19,462%SkBFmax·s ([11,346,27,579]; p<0.001) compared to CTRL. For LTH, EMLA delayed onset time by 76s ([46,106]; p<0.001) Pre-IR and by 46s ([27,65]; p<0.001) Post-IR compared to CTRL. Post-IR onset time was delayed for CTRL by 26s ([8,43]; p=0.007), but was not different for EMLA (p>0.050) compared to Pre-IR. EMLA delayed time to initial peak by 24s ([4,43]; p=0.022, Main time effect) and it attenuated the initial peak by 27%SkBFmax ([12,43]; p=0.002) Pre-IR and by 16%SkBFmax ([3,29]; p=0.020) post-IR compared to CTRL. Post-IR, the initial peak was not different for CTRL (p>0.050), but it was increased by 16%SkBFmax ([5,26]; p=0.005) for EMLA compared to Pre-IR. Neither EMLA nor IR altered the steady-state heating plateau (all p>0.050). For the current model of IR injury, sensory nerves appear to have a negligible influence on the LTH response in non-glabrous forearm skin once vasodilation has been initiated.

Two Weeks Of Remote Ischemic Preconditioning Improved Cutaneous Microvascular Responses To Post-occlusive Reactive Hyperemia

PURPOSE: Repeated remote ischemic preconditioning (RIPC), induced by intermittent periods of ischemia and reperfusion in a limb body, improves non-nitric oxide (NO)-mediated endothelial-dependent cutaneous vasodilation. Post-occlusive reactive hyperemia (PORH) occurs following the release of a brief arterial occlusion and is principally mediated by non-NO mediated vasodilatory factors such as prostaglandins, sensory nerve axon reflex, and endothelium-derived hyperpolarizing factors (EDHFs). However, the role of repeated bouts of RIPC on the PORH response is unknown. The purpose of this study was to test whether two weeks of RIPC improves PORH elicited cutaneous microvascular hyperemia responses. METHODS: The study was conducted with twenty-one participants (Control; 24 ± 5 yr old, 4 M/4F, n = 8, RIPC; 22 ± 2 yr old, 7 M/6F, n = 13). The RIPC group received RIPC daily sessions over a two-week period (3 intervals of 4 days with RIPC followed by a 1 day break). Each RIPC session consisted of 4 repetitions of 5-minute arm blood flow occlusion interspersed by 5-minute reperfusion. PORH was elicited by brachial artery occlusion for 5 minutes by inflating an arm cuff to 200 mmHg, and the cutaneous hyperemic response was measured after cuff release. Skin blood flow measurements were collected with laser speckle contrast image (LSCI) before and after the repeated RIPC intervention. The control group did not receive RIPC but underwent repeated PORH measurements two weeks later. RESULTS: Both Time to Peak (Tp) and max/time improved after two weeks of RIPC (Tp; 16.5 ± 2.1 vs.15.2 ± 2.9 s, Pre vs. Post, p < 0.05, max/time; 0.11 ± 0.03 vs. 0.13 ± 0.04 CVC/s, Pre vs. Post, p < 0.05). The control group did not change after 2 weeks. CONCLUSIONS: These data suggest that non-NO mediated vasodilator responses in the skin microvasculature may be affected with 2 weeks of repeated RIPC.

HIGH MOBILITY GROUP BOX-1 IS INCREASED IN NEWLY DIAGNOSED ESSENTIAL HYPERTENSIVES AND CORRELATES WITH HYPERTENSION-MEDIATED TARGET ORGAN DAMAGE

Objective: Chronic immune-mediated inflammation is increasingly recognized as an important contributor to target organ damage (TOD) in essential hypertension (EH). High mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule which stimulates innate immunity, hence exerting significant proinflammatory properties including vascular inflammation and thrombosis. So far, no clinical data exist regarding the role of HMGB1 in EH and its association with vascular damage. Our objective was to measure HMGB1 levels in newly diagnosed, untreated patients with EH (UHTs) compared to normotensive controls (NTs) and correlate them with indices of macro- and microvascular dysfunction, which play a core role in the pathogenesis of TOD in EH. Design and method: HMGB1 was measured in serum with ELISA. Ambulatory and central blood pressure (BP) parameters, and pulse wave velocity (PWV), were measured by using the Mobil-O-Graph device. Skin microcirculation was assessed with Laser Speckle Contrast Imaging (LSCI) coupled with post-occlusive reactive hyperemia (PORH). Results are expressed as a percentage increase between peak and baseline perfusion (%), and the amplitude of PORH response defined as peak Cutaneous Vascular Conductance (CVC) minus baseline CVC. The CVC was calculated as the flux in each period divided by mean arterial pressure [(PUs)/mmHg]. Results: We consecutively enrolled 55 UHTs and 25 NTs matched for age and sex. HMGB1 levels were significantly higher in UHTs compared to NTs. HMGB1 showed a significant positive association with measures of macrocirculation including 24 h central systolic (0.325, p &lt; 0.01) and diastolic BP (0.371, p &lt; 0.01), day central systolic (0.353, p &lt; 0.01) and diastolic BP (0.402, p &lt; 0.01), and 24 h PWV (0.224, p &lt; 0.05) and day PWV (0.230, p &lt; 0.05) in the total study population. In addition, HMGB1 presented a significant negative association with skin microvascular parameters including base to peak flux (-0.247, p &lt; 0.05) and PORH amplitude (-0.225, p &lt; 0.01). Conclusions: HMGB1 is significantly increased in UHTs compared to NTs and correlates with indices of macro- and microvascular damage. These results reinforce the concept that immune system activation contributes to hypertension-mediated TOD from the very early stages and point towards intense research in order to investigate novel potential therapeutic targets related to EH.

Effects of regular physical exercise on skin blood flow and cardiovascular risk factors in overweight and obese subjects

Objective: it is well known that low omentin levels and reduced bioavailability of nitric oxide (NO) are outgrowth of obesity. Besides, in obese subjects, microvascular dysfunction can be an initial stage of cardiovascular diseases. This situation can be evaluated with skin laser–Doppler flowmetry (LDF).Methods: in this study we investigated the effects of 12 weeks moderate physical exercise on microvascular reactivity and plasma levels of omentin and NO in 25 overweight and obese subjects. Control group was composed of 28 sedentary participants who were neither obese nor overweight. Microvascular reactivity was handled by measurement of skin blood flow from the ring finger of the right hand with LDF, which is a non–invasive method for evaluation. With this method, it was aimed to examine the post–occlusive reactive hyperemia response of the patients. None of the participants in both groups have never followed a regular exercise schedule in their life span.Results: with regular exercise, there was a statistically significant decrease in glucose (p=0.008), cholesterol (p=0.05), and triglyceride (p=0.048) levels, while body mass index, high–density lipoprotein, and low–density lipoprotein levels did not change significantly in overweight/obese group. Also, the omentin level significantly increased (p=0.01), but NO level did not change significantly. Moreover, the amount of change in omentin and NO levels measured before and after the physical exercise were significantly correlated (r=0.57). Considering the microcirculation, rest flow (p=0.001) and peak flow value of LDF (p=0.001) increased after the physical exercise.Conclusion: our study shows that moderate physical exercise affects microvascular reactivity and plasma levels of omentin in overweight and obese subjects.

Oral Glucose Load and Human Cutaneous Microcirculation: An Insight into Flowmotion Assessed by Wavelet Transform.

Simple SummaryThere is increasing evidence to suggest that microcirculation becomes dysfunctional earlier than large blood vessels or the heart in several diseases. In diabetes mellitus, a disease characterized by chronic hyperglycemia, microvascular impairment is well-established; on the contrary, the effect of acute hyperglycemia in microcirculation remains unclarified. Our aim was to investigate the microvascular effect of an oral glucose load (OGL) using laser Doppler flowmetry (LDF) as a perfusion quantification technique, coupled with wavelet transform (WT) to perform a spectral decomposition of the LDF signal. On two distinct occasions (pre-load and post-load), sixteen healthy subjects drank either a standard glucose solution or water. Perfusion was assessed by LDF and WT while resting and during post-occlusive reactive hyperemia (PORH), evoked by a transient three-min occlusion of the brachial artery, in the forearm and the finger pulp. The OGL affected microcirculation in both sites compared to water, significantly blunting the PORH response in the forearm. The WT revealed significant differences in the cardiac and sympathetic components after OGL between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system.Microcirculation in vivo has been assessed using non-invasive technologies such as laser Doppler flowmetry (LDF). In contrast to chronic hyperglycemia, known to induce microvascular dysfunction, the effects of short-term elevations in blood glucose on microcirculation are controversial. We aimed to assess the impact of an oral glucose load (OGL) on the cutaneous microcirculation of healthy subjects, quantified by LDF and coupled with wavelet transform (WT) as an interpretation tool. On two separate occasions, sixteen subjects drank either a glucose solution (75 g in 250 mL water) or water (equal volume). LDF signals were obtained in two anatomical sites (forearm and finger pulp) before and after each load (pre-load and post-load, respectively), in resting conditions and during post-occlusive reactive hyperemia (PORH). The WT allowed decomposition of the LDF signals into their spectral components (cardiac, respiratory, myogenic, sympathetic, endothelial NO-dependent). The OGL blunted the PORH response in the forearm, which was not observed with the water load. Significant differences were found for the cardiac and sympathetic components in the glucose and water groups between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system.

HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS HAVE SEVERELY IMPAIRED ENDOTHELIAL POST-OCCLUSIVE FOREARM VASODILATORY RESPONSE ASSESSED WITH LASER SPECKLE CONTRAST IMAGING

Abstract Objective: Endothelial dysfunction is associated with cardiovascular events and mortality in various disease states, including end-stage-renal-disease (ESRD). Novel technological approaches have emerged for real-time assessment of endothelial reactivity. This study examined forearm skin microcirculation using Laser Speckle Contrast Imaging (LSCI) before and after arterial occlusion in ESRD patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Design and method: Thirty-eight patients undergoing HD were matched in a 1:1 ratio with 38 PD patients (for age, sex and dialysis vintage) and 38 controls (for age and sex). Skin microvascular reactivity parameters assessed with LSCI included baseline perfusion, occlusion perfusion, and peak perfusion during post-occlusive reactive hyperemia (PORH); time to peak perfusion; proportional change from baseline to peak perfusion; baseline and peak cutaneous vascular conductance (CVC); proportional change from baseline to peak CVC; and the amplitude of the PORH response (calculated as the difference between peak and baseline CVC). Results: Baseline perfusion [HD: 46.97 ± 14.6; PD: 49.32 ± 18.07; controls: 42.02 ± 11.94 Laser-Specle-Perfusion-Units (LSPU), p = 0.097] and peak post-occlusion perfusion (104.77 ± 28.68 vs 109.04 ± 40.77 vs 116.96 ± 30.96 LSPU, p = 0.238) did not differ between groups. However, the post-occlusive vascular response was completely different, since time to peak response (HD: 7.24 ± 6.99; PD: 10.68 ± 9.45; controls: 11.11 ± 5.1 sec, p = 0.003) and the (%) increase from baseline to peak perfusion (HD: 133% ± 66; PD: 149% ± 125; controls: 187% ± 61, p = 0.001) was significantly lower in ESRD patients. ESRD patients had also lower levels of peak CVC, indicating the maximum capillary recruitment (HD: 1.05 ± 0.3; PD: 1.07 ± 0.44; controls: 1.57 ± 0.52 LSPU/mmHg, p &lt; 0.001), lower % increase of CVC at peak (p = 0.001), and lower amplitude of the PORH response (p = 0.001) (a measure of the difference between baseline and maximum capillary recruitment). Conclusions: Using this novel non-invasive technology endothelial post-occlusive skin vasodilatory response was found to be similar between HD and PD patients and significantly impaired compared to controls. Future studies are needed to assess the prognostic implications of this microcirculatory functional defect.

MASKED HYPERTENSIVES AS ASSESSED WITH LASER SPECKLE CONTRAST IMAGING EXHIBIT IMPAIRED SKIN MICROVASCULAR REACTIVITY SIMILAR TO ESSENTIAL HYPERTENSIVE INDIVIDUALS

Objective: Laser Speckle Contrast Imaging (LSCI) is a novel method to dynamically assess skin microcirculation with very high resolution and reproducibility compared to other laser methods. Skin microcirculation has been proposed as a model of generalized microvascular function and a potential biomarker in cardiovascular prognosis. Masked hypertension is considered a hypertension phenotype of substantial cardiovascular risk similar to essential hypertension (EH). In this study we evaluated skin microvascular reactivity in masked hypertensives as compared to hypertensives and healthy, normotensive individuals using LSCI coupled with post-occlusive reactive hyperemia (PORH) test. Design and method: We included 20 newly diagnosed masked hypertensives aged 50.0 ± 9.0 and compared them to 70 never treated, newly diagnosed patients with EH aged 49.5 ± 8.7 and 40 healthy, normotensive individuals aged 48.5 ± 8.5 years. Hypertension phenotypes were defined according to standard office and ambulatory blood pressure monitoring (ABPM) criteria. The Mobil-O-Graph-NG (IEM, Stolberg, Germany) device was used for ABPM. All subjects underwent forearm skin perfusion recording under standardized conditions using a LSCI device (PeriCam PSI NR System, Perimed, Järfälla, Sweden) coupled with PORH. Data were analyzed by manufacturer's software (PIMSoft, Perimed). Results were expressed as i) the percentage increase of perfusion from baseline to peak condition (%), and ii) the amplitude of PORH response expressed as the peak cutaneous vascular conductance (CVC) minus baseline CVC. The CVC was calculated as the flux of each time interval divided by mean arterial pressure (perfusion units [PU]/mmHg). Results: Masked hypertensives showed significantly lower percentage increase of perfusion from baseline to peak condition as compared to controls (155.4 ± 48.11 vs 190.54 ± 45.88, p = 0.013) but not compared to hypertensives (155.4 ± 48.11 vs 150.6 ± 41.93, p = NS), respectively. In addition, PORH amplitude was significantly lower in masked hypertensives as compared to controls (0.62 ± 0.2 vs 0.76 ± 0.2, p = 0.02) but no difference was found compared to hypertensives (0.62 ± 0.2 vs 0.52 ± 0.1, p = NS), respectively. Conclusions: Masked hypertensives, when assessed with LSCI coupled with PORH, present impaired skin microvascular reactivity as compared to healthy controls. However, their skin microvascular responses were similar to those of hypertensives, highlighting a state of increased microvascular damage in this hypertension phenotype.

Reproducibility and normalization of reactive hyperemia using laser speckle contrast imaging.

BackgroundImpaired perfusion indices signal potential microvascular dysfunction preceding atherosclerosis and other cardiometabolic pathologies. Post-occlusive reactive hyperemia (PORH), a vasodilatory response following a mechanically induced ischemia, is a transient increase in perfusion and can assess microvascular function. The greatest blood flow change corresponding to the first minute of hyperemia (represented by time-to-peak, hyperemic velocity, AUC within 1st min) has been shown to indicate microvascular dysfunction. However, the reproducibility of these temporal kinetic indices of the PORH response is unknown. Our aim was to examine the inter- and intra-day reproducibility and standardization of reactive hyperemia, with emphasis on the kinetic indices of PORH, using laser speckle contrast imaging (LSCI) technique.Methods and resultsSeventeen healthy adults (age = 24 ± 3 years) completed three PORH bouts over two lab visits. LSCI region of interest was a standardized 10 cm region on the dominant ventral forearm. A 5-min brachial artery occlusion period induced by inflating an arm cuff to 200 mmHg, preceded a 4-min hyperemic period. Inter- and intra-day reliability and reproducibility of cutaneous vascular conductance (LSCI flux / mean arterial pressure) were determined using intraclass correlation (ICC) and coefficient of variation (CV%). Maximal flow and area under the curve standardized to zero perfusion showed intra- and inter-day reliability (ICC > 0.70). Time to maximal flow (TMF) was not reproducible (inter-day CV = 18%). However, alternative kinetic indices such as 1-min AUC and overshoot rate-of-change (ORC), represented as a piecewise function (at 5s, 10s, 15s, and 20s into hyperemia), were reproducible (CV< 11%). Biological zero was a reliable normalization point.ConclusionPORH measured with LSCI is a reliable assessment of microvascular function. However, TMF or its derived hyperemic velocity are not recommended for longitudinal assessment. Piecewise ORC and 1-min AUC are reliable alternatives to assess the kinetic response of PORH.

Haemodialysis and peritoneal dialysis patients have severely impaired post-occlusive skin forearm vasodilatory response assessed with laser speckle contrast imaging.

BackgroundEndothelial dysfunction is associated with cardiovascular events and mortality in various disease states, including end-stage renal disease (ESRD). Novel technological approaches have emerged for real-time assessment of endothelial reactivity. This study examined skin microcirculation using laser speckle contrast imaging (LSCI) before and after arterial occlusion in ESRD patients undergoing haemodialysis (HD) or peritoneal dialysis (PD).MethodsThe 38 HD patients were matched in a 1:1 ratio with 38 PD patients (for age, sex and dialysis vintage) and 38 controls (for age and sex). Skin microvascular reactivity parameters assessed with LSCI included baseline perfusion, occlusion perfusion and peak perfusion during post-occlusive reactive hyperaemia (PORH); time to peak perfusion; proportional change from baseline to peak perfusion; baseline and peak cutaneous vascular conductance (CVC); proportional change from baseline to peak CVC and amplitude of the PORH response (i.e. the difference between peak and baseline CVC).ResultsBaseline perfusion [HD: 46.97 ± 14.6; PD: 49.32 ± 18.07; controls: 42.02 ± 11.94 laser specle perfusion units (LSPU), P = 0.097] and peak post-occlusion perfusion (104.77 ± 28.68 versus 109.04 ± 40.77 versus 116.96 ± 30.96 LSPU, P = 0.238) did not differ significantly between groups. However, the post-occlusive vascular response was completely different since the proportional increase from baseline to peak perfusion (HD: 133 ± 66; PD: 149 ± 125; controls: 187 ± 61%, P = 0.001) was significantly lower in ESRD patients and time to peak response was lower in HD but similar in PD patients compared with controls (HD: 7.24 ± 6.99; PD: 10.68 ± 9.45; controls: 11.11 ± 5.1 s, Kruskal–Wallis P = 0.003; pairwise comparisons: HD versus controls, P = 0.002; HD versus PD, P = 0.154; PD versus controls, P = 0.406). ESRD patients also had lower levels of peak CVC, indicating the maximum capillary recruitment (HD: 1.05 ± 0.3; PD: 1.07 ± 0.44; controls: 1.57 ± 0.52 LSPU/mmHg, P < 0.001), lower proportional increase of CVC at peak (P < 0.001) and lower amplitude of the PORH response, a measure of the difference between baseline and maximum capillary recruitment (P = 0.001).ConclusionsUsing this novel non-invasive technology, endothelial post-occlusive forearm skin vasodilatory response was found to be similar between HD and PD patients and significantly impaired compared with controls. Future studies are needed to assess the prognostic implications of this microcirculatory functional defect.

P0162HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS HAVE SEVERELY IMPAIRED ENDOTHELIAL POST-OCCLUSIVE FOREARM VASODILATORY RESPONSE ASSESSED WITH LASER SPECKLE CONTRAST IMAGING

Abstract Background and Aims Endothelial dysfunction is associated with cardiovascular events and mortality in various disease states, including end-stage-renal-disease (ESRD). Novel technological approaches have emerged for real-time assessment of endothelial reactivity. This study examined forearm skin microcirculation using Laser Speckle Contrast Imaging (LSCi) before and after arterial occlusion in ESRD patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) Method 38 patients undergoing HD were matched in a 1:1 ratio with 38 PD patients (for age, sex and dialysis vintage) and 38 controls (for age and sex). Skin microvascular reactivity parameters assessed with LSCI included baseline perfusion, occlusion perfusion, and peak perfusion during post-occlusive reactive hyperemia (PORH); time to peak perfusion; proportional change from baseline to peak perfusion; baseline and peak cutaneous vascular conductance (CVC); proportional change from baseline to peak CVC; and the amplitude of the PORH response (calculated as the difference between peak and baseline CVC). Results Baseline perfusion [HD: 46.97±14.6; PD: 49.32±18.07; controls: 42.02±11.94 Laser-Specle-Perfusion-Units (LSPU), p=0.097] and peak post-occlusion perfusion (104.77±28.68 vs 109.04±40.77 vs 116.96±30.96 LSPU, p=0.238) did not differ between groups. However, the post-occlusive vascular response was completely different, since time to peak response (HD: 7.24±6.99; PD: 10.68±9.45; controls: 11.11±5.1 sec, p=0.003) and the (%) increase from baseline to peak perfusion (HD: 133%±66; PD: 149%±125; controls: 187%±61, p=0.001) was significantly lower in ESRD patients. ESRD patients had also lower levels of peak CVC, indicating the maximum capillary recruitment (HD: 1.05±0.3; PD: 1.07±0.44; controls: 1.57±0.52 LSPU/mmHg, p&amp;lt;0.001), lower % increase of CVC at peak (p=0.001), and lower amplitude of the PORH response (p=0.001) (a measure of the difference between baseline and maximum capillary recruitment). Conclusion Using this novel non-invasive technology endothelial post-occlusive skin vasodilatory response was found to be similar between HD and PD patients and significantly impaired compared to controls. Future studies are needed to assess the prognostic implications of this microcirculatory functional defect.

Assessment of tissue perfusion and vascular function in mice by scanning laser Doppler perfusion imaging

Post-occlusive reactive hyperemia (PORH) is a key feature of physiological vasomotion to appropriately match the supply/demand ratio of tissues. This adaptive mechanism is severely disturbed in endothelial dysfunction with a reduced flow-mediated dilation (FMD). Reduced PORH and FMD are powerful prognostic risk factors in cardiovascular diseases. While these parameters are frequently determined in human beings, comparable methods applicable to mouse models are sparse. We aimed to evaluate the applicability and accuracy of scanning laser Doppler perfusion imaging (LDPI) to measure PORH in the mouse hindlimb. Changes in mean perfusion in response to vasoactive drugs and PORH (assessed by scanning LDPI) were compared with changes in diameter and blood flow in the femoral artery, as assessed by high-resolution ultrasound. We found that the measured LDPI signal significantly correlated with changes of inflow into the femoral artery. Vasodilation induced by administration of nitroglycerine and acetylcholine increased vessel diameter, blood flow and mean perfusion, while vasoconstriction following administration of epinephrine decreased all three parameters. PORH was induced by temporal occlusion of the femoral artery with an external cuff. During occlusion, mean perfusion decreased to a condition of zero-perfusion and release of the cuff induced an immediate increase in blood flow that was followed by femoral artery dilation driving PORH/perfusion. Surgical removal of the femoral artery decreased mean perfusion to a zero-perfusion level and fully abolished PORH. Importantly, the measurement of the PORH response by scanning LDPI is highly reproducible as determined by repeated measurements and intra/interobserver variation analysis. Last, we found that the PORH response was dependent on nitric oxide synthase and cyclooxygenase and declined with age. Thus, we here provide novel and robust non-invasive methods to serially measure tissue perfusion at baseline and during physiological and pharmacological modulation of vasomotor tone in the hindlimb of mice. The application of these LDPI scanning and ultrasound-based methods may be useful for testing the effects of drugs affecting vasomotor function or future elucidation of mechanisms leading to vasomotor dysfunction in mice in vivo.

The Effect of High Intensity Interval Training Versus Steady State Aerobic Training on Skin Microvascular Reactivity in Moderately Active Young Adults: A Pilot Study

A sedentary lifestyle is associated with endothelial dysfunction, leading to vascular pathology and impaired microvascular reactivity (MVR). Enhanced endothelial functioning has been seen in aerobically trained individuals. The purpose of this study was to determine if there was a differential training response of skin MVR in response to high intensity aerobic interval training (HIAIT) as compared to steady state aerobic training (SSAT). The study involved 16 moderately active male students (age: 20.93 &amp;plusmn; 5.05 yrs). They were randomly assigned to one of three groups; HIAIT, SSAT, and control group (CG). Baseline testing was performed to determine the VO2max, lactate threshold, blood pressure, body composition and a post-occlusive reactive hyperemia response (PORH) test was used to assess microvascular reactivity on the right palmer forearm using a moorVMS-Laser Doppler Flowmetry (LDF) These parameters were reassessed after three weeks (mid-point) and six-weeks (post intervention) weeks. Statistical significance was set at p&amp;le;0.05. There were no significant interactions between the variables measured in the three groups over time. There was a positive linear relationship in the SSAT group for PORHmax/time to peak (Tp) at baseline (r = 0.998, p = 0.039), midpoint (r = 0.992, p = 0.083), and the post intervention (r = 0.987, p = 0.103). Training in the SSAT group had improved PORHpeak at midpoint and post intervention time points (r = 0.999, p = 0.22; r = 1, p = 0.006; r = 1, p = 0.011). Training in either the HIAIT or the SSAT group had no significant effect on skin MVR in moderately active young adults. SSAT did display a positive linear relationship with PORHmax/Tp, and PORHpeak, which are variables influencing skin MVR.

Application of cmOCT and continuous wavelet transform analysis to the assessment of skin microcirculation dynamics.

Correlation mapping optical coherence tomography (cmOCT) is a powerful technique for the imaging of skin microvessels structure, based on the discrimination of the static and dynamic regions of the tissue. Although the suitability of cmOCT to visualize the microcirculation has been proved in humans and animal models, less evidence has been provided about its application to examine functional dynamics. Therefore, the goal of this research was validating the cmOCT method for the investigation into microvascular function and vasomotion. A spectral domain optical coherence tomography (SD-OCT) device was employed to image 90 sequential three-dimensional (3-D) OCT volumes from the forearm of 12 volunteers during a 25-min postocclusive reactive hyperemia (PORH) test. The volumes were processed using cmOCT to generate blood flow maps at selected cutaneous depths. The maps clearly trace flow variations during the PORH response for both capillaries and arterioles/venules microvascular layers. Continuous blood flow signals were reconstructed from cmOCT maps to study vasomotion by applying wavelet transform spectral analysis, which revealed fluctuations of flow during PORH, reflecting the regulation of microvascular tone mediated by endothelial cells and sympathetic nerves. The results clearly demonstrate that cmOCT allows the generation of functional information that may be used for diagnostic applications.

The effect of repeated bouts of hyperaemia on sensory nerve-mediated cutaneous vasodilatation in humans

PurposeTo investigate cutaneous sensory nerve contribution to hyperaemia following chronic shear stress training. MethodsEleven males underwent a shear stress intervention (forearm occlusion 5 s, rest 10 s) for 30 min, 5 times·week−1 for 6 weeks on one arm, the other was an untreated control. Skin blood flow was measured using laser-Doppler flowmetry, and sensory nerve function was assessed with and without blockade with EMLA cream in response to 3 levels of local heating (39, 42, and 44 °C) and post-occlusive reactive hyperaemia (PORH). ResultsIn response to local heating, EMLA treatment significantly delayed the onset of vasodilatation (p < 0.001), time-to-peak (p < 0.001), time to 39 °C (p < 0.02), time to 42 °C (p < 0.006), but not time to 44 °C (p > 0.2). EMLA treatment also increased time-to-peak for PORH (p ≤ 0.01). In the experimental limb after 6 weeks, both onset time and time to peak were shorter in response to local heating at the untreated and EMLA-treated sites (all p < 0.001). There were no changes in time-to-peak for PORH at the untreated and EMLA-treated sites (p ≥ 0.4); however, the peak PORH response was reduced with EMLA treatment (p ≤ 0.03). The 6-week intervention increased the peak PORH at the untreated sites (p < 0.001) but not at EMLA-treated (p > 0.05) sites. Comparing the control limb before and after 6 weeks, no differences in responses occurred at either the untreated skin sites (p ≥ 0.9) or the EMLA-treated sites (p ≥ 0.9). ConclusionsSensory nerve blockade attenuated the improvements in cutaneous vascular responses to thermal hyperaemia and PORH following chronic exposure to shear stress. These data demonstrate an important role for sensory nerve function in the initiation of vasodilatation to both PORH and thermal hyperaemia, in both the time to onset and the magnitude of vasodilatation.

Acute exhaustive rowing exercise reduces skin microvascular dilator function in young adult rowing athletes.

The effect of acute exhaustive exercise session on skin microvascular reactivity was assessed in professional rowers and sedentary subjects. A potential involvement of altered hemodynamic parameters and/or oxidative stress level in the regulation of skin microvascular blood flow by acute exercise were determined. Anthropometric, biochemical, and hemodynamic parameters were measured in 18 young healthy sedentary men and 20 professional rowers who underwent a single acute exercise session. Post-occlusive reactive hyperemia (PORH), endothelium-dependent acetylcholine (ACh), and endothelium-independent sodium nitroprusside (SNP) microvascular responses were assessed by laser Doppler flowmetry in skin microcirculation before and after acute exercise. Serum lipid peroxidation products and plasma antioxidant capacity were measured using spectrophotometry. At baseline, rowers had significantly lower diastolic blood pressure (DBP) and heart rate (HR), and higher stroke volume (SV), PORH, and endothelium-dependent vasodilation than sedentary. Acute exercise caused a significant increase in systolic blood pressure, DBP, HR, and SV and a decrease in total peripheral resistance in both groups. Acute exercise induced a significant impairment in PORH and ACh-induced response in rowers, but not in sedentary, whereas the SNP-induced vasodilation was not affected by acute exercise in any group. Antioxidant capacity significantly increased only in sedentary after acute exercise. Single acute exercise session impaired microvascular reactivity and endothelial function in rowers but not in sedentary, possibly due to (1) more rowing grades and higher exercise intensity achieved by rowers; (2) a higher increase in arterial pressure in rowers than in sedentary men; and (3) a lower antioxidant capacity in rowers.

PulseCam: high-resolution blood perfusion imaging using a camera and a pulse oximeter.

Measuring blood perfusion is important in medical care as an indicator of injury and disease. However, currently available devices to measure blood perfusion like laser Doppler flowmetry are bulky, expensive, and cumbersome to use. An alternative low-cost and portable camera-based blood perfusion measurement system has recently been proposed, but such camera-only system produces noisy low-resolution blood perfusion maps. In this paper, we propose a new multi-sensor modality, named PulseCam, for measuring blood perfusion by combining a traditional pulse oximeter with a video camera in a unique way to provide low noise and high-resolution blood perfusion maps. Our proposed multi-sensor modality improves per pixel signal to noise ratio of measured perfusion map by up to 3 dB and improves the spatial resolution by 2 - 3 times compared to best known camera-only methods. Blood perfusion measured in the palm using our PulseCam setup during a post-occlusive reactive hyperemia (PORH) test replicates standard PORH response curve measured using laser Doppler flowmetry device but with much lower cost and a portable setup making it suitable for further development as a clinical device.

Microcirculation in healing and healthy Achilles tendon assessed with invasive laser doppler flowmetry.

Achilles tendon (AT) rupture exhibits a prolonged healing process with varying clinical outcome. Reduced blood flow to the AT has been considered an underlying factor to AT rupture (ATR) and impaired healing. In vivo measurements using laser Doppler flowmetry (LDF) may be a viable method to assess blood flow in healthy and healing AT. 29 persons were included in the study; 9 being ATR patients and 20 healthy subjects without any prior symptoms from the AT. Invasive LDF was used to determine the post-occlusive reactive hyperemia (PORH) in the paratenon after 15 minutes of occlusion of the lower extremities. ATR patients were examined two weeks post-operatively. LDF-assessments demonstrated a significantly different (p < 0.001) PORH response in the healing- versus intact- and control AT. In the healing AT, a slow, flattened PORH was observed compared to a fast, high peak PORH in intact, healthy AT. in vivo LDF appears to be a feasible method to assess alterations in blood flow in healing and intact AT. The healing ATs capability to react to an ischemic period is clearly impaired, which may be due to the trauma at injury and/or surgery or degenerative changes in the tendon.

Skin Microvascular Reactivity in Young Adults in Relation to Maximal and Submaximal Indices of Cardiorespiratory Fitness

Low cardiorespiratory fitness (CRF) is associated with endothelial dysfunction and decreased microvascular reactivity that increases risk for cardiovascular disease. Enhanced endothelial functioning is associated with CRF, specifically maximal aerobic capacity. However, the effect of submaximal indices of CRF, such as ventilatory threshold (VT) and respiratory compensation point (RCP), on microvascular reactivity is unclear. PURPOSE: To determine the association between maximal and submaximal indices of CRF and skin microvascular reactivity in physically active, untrained young adults. METHODS: Twenty-six physically active, untrained, young adults (21.6 ±1.9 yrs, 73.3 ±10.5 kg, BMI 23.7 ±2.9 kg.m2) were recruited. An incremental bicycle ergometer test was then performed to determine VO2peak, VT and RCP. One week later, a post-occlusive reactive hyperemia response (PORH) test was used to assess microvascular reactivity on the subject’s right palmer forearm using a moorVMS-Laser Doppler Fluxmeter (LDF). Defined flux and time parameters were calculated from the PORH test including PORHmax (maximum increase in hyperemia perfusion above resting flux), PORHpeak (amplitude of peak perfusion), time-to-peak perfusion (Tp) and the ratio of PORHmax/Tp. Multiple linear regression (backward method) was used to determine the association between variables. Significance was set at P<0.05. RESULTS: The results for VO2peak (46.65 ± 7.48 ml/kg.min-1), VT (34.67 ± 12.62 % of VO2peak) and RCP (74.88 ± 19 % of VO2peak) indicated a moderate maximal aerobic capacity but low submaximal endurance capacity for the participants. Maximal and submaximal CRF indices were shown to be strongly associated with microvascular reactivity. Specifically, VO2peak was shown to be the best predictor of PORHmax (r2 = 0.18; p=0.03). VT was shown to be the best predictor of PORHpeak (r2 = 0.17; p=0.04), TP (r2 = 0.11; P=0.04) and PORHmax/ TP (r2 = 0.18; P=0.02). RCP together with VT predicted 28% of the variance in PORHmax/ TP (r2 = 0.28; P=0.02) CONCLUSION: Maximal and submaximal indices of cardiorespiratory fitness, specifically VO2 peak and VT are independent predictors of microvascular reactivity. The finding that VT, a submaximal index of cardiorespiratory fitness, predicts most microvascular reactivity parameters has implications for exercise interventions aimed at improving microvascular health and reducing cardiovascular risk.

Post‐Occlusive Reactive Hyperemia: Effects on Skeletal Muscle Capillary Hemodynamics

Post‐occlusive reactive hyperemia (PORH) is the commonly accepted non‐invasive diagnostic test used for evaluating endothelial function in humans. In contrast to conduit brachial artery blood flow, little is known regarding capillary hemodynamics during PORH. An understanding of microcirculatory behavior post occlusion is fundamental to interpreting the PORH response. Based on previous results found in humans we tested the hypothesis that mechanically induced ischemia of the spinotrapezius muscle would increase the percentage of capillaries supporting red blood cell (RBC) flux during reperfusion. Capillary hemodynamics were measured via intravital microscopy in young male Sprague‐Dawley rats at baseline (BL), during mechanical feed artery occlusion (OCC, 1 min and 5 min) and subsequent reperfusion. Mean arterial pressure and heart rate were not altered (both P &gt; 0.05). As expected, the percentage of capillaries supporting RBC flux was reduced during 1 min OCC (BL: 90 ± 3, OCC: 2 ± 2%, P &lt; 0.05) and 5 min OCC (BL: 87 ± 3, OCC: 0 ± 0%, P &lt;0.05). At 30 s reperfusion the percentage of capillaries supporting RBC flux decreased relative to BL following 1 min OCC (BL: 90 ± 3%, reperfusion: 85 ± 3%, P &lt; 0.05) and 5 min OCC (BL: 87 ± 3, reperfusion: 29 ± 3%, P &lt; 0.05). Thus during reperfusion the percentage of capillaries supporting RBC flux neither exceeded nor even returned to BL levels up to 5 min post OCC thereby demonstrating impaired capillary function and thus blood‐myocyte O2 and substrate flux. Consequently, the PORH state in the spinotrapezius muscle of the rat differs markedly from physiological contraction‐induced hyperemia found in humans.Grants: NIH HL‐108328 NIH T32OD011169

Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms.

Cardiovascular benefits from estradiol activation of nitric oxide endothelial production may depend on vascular wall and on estrogen receptor alpha (ESR1) and nitric oxide synthase (NOS3) polymorphisms. We have evaluated the microcirculation in vivo through nailfold videocapillaroscopy, before and after acute nasal estradiol administration at baseline and after increased sheer stress (postocclusive reactive hyperemia response) in 100 postmenopausal women, being 70 controls (healthy) and 30 simultaneously hypertensive and diabetic (HD), correlating their responses to PvuII and XbaI ESR1 polymorphisms and to VNTR, T-786C and G894T NOS3 variants. In HD women, C variant allele of ESR1 Pvull was associated to higher vasodilatation after estradiol (1.72 vs 1.64 mm/s, p = 0.01 compared to TT homozygotes) while G894T and T-786C NOS3 polymorphisms were connected to lower increment after shear stress (15% among wild type and 10% among variant alleles, p = 0.02 and 0.04). The G variant allele of ESR1 XbaI polymorphism was associated to higher HOMA-IR (3.54 vs. 1.64, p = 0.01) in HD and higher glucose levels in healthy women (91.8 vs. 87.1 mg/dl, p = 0.01), in which increased waist and HOMA-IR were also related to the G allele in NOS3 G894T (waist 93.5 vs 88.2 cm, p = 0.02; HOMA-IR 2.89 vs 1.48, p = 0.05). ESR1 Pvull, NOS3 G894T and T-786C polymorphism analysis may be considered in HD postmenopausal women for endothelial response prediction following estrogen therapy but were not discriminatory for endothelial response in healthy women. ESR1 XbaI and G894T NOS3 polymorphisms may be useful in accessing insulin resistance and type 2 diabetes risks in all women, even before menopause and occurrence of metabolic disease.