Suprasystolic Occlusion Research Articles

Mechanisms maintaining cerebral perfusion during systemic hypotension are impaired in elderly adults.

Postural hypotension abruptly lowers cerebral perfusion, producing unsteadiness which worsens with aging. This study addressed the hypothesis that maintenance of cerebral perfusion weakens in the elderly due to less effective cerebrovascular autoregulation and systemic cardiovascular responses to hypotension. In healthy elderly (n = 13, 68 ± 1 years) and young (n = 13, 26 ± 1 years) adults, systemic hypotension was induced by rapid deflation of bilateral thigh cuffs after 3-min suprasystolic occlusion, while heart rate (HR), mean arterial pressure (MAP), and blood flow velocity of the middle cerebral artery (VMCA) were recorded. VMCA/MAP indexed cerebrovascular conductance (CVC). Durations and rates of recovery of MAP and VMCA from their respective postdeflation nadirs were compared between the groups. Thigh-cuff deflation elicited similar hypotension and cerebral hypoperfusion in the elderly and young adults. However, the time elapsed (TΔ) from cuff deflation to the nadirs of MAP and VMCA, and the time for full recovery (TR) from nadirs to baselines were significantly prolonged in the elderly subjects. The response rates of HR (ΔHR, i.e. cardiac factor), MAP (ΔMAP, i.e. vasomotor factor), and CVC following cuff deflation were significantly slower in the elderly. Collectively, the response rates of the cardiac, vasomotor, and CVC factors largely explained TRVMCA. However, the TRVMCA/ΔMAP slope (-3.0 ± 0.9) was steeper (P = 0.046) than the TRVMCA/ΔHR slope (-1.1 ± 0.4). The TRVMCA/ΔCVC slope (-2.4 ± 0.6) was greater (P = 0.072) than the TRVMCA/ΔHR slope, but did not differ from the TRVMCA/ΔMAP slope (P = 0.52). Both cerebrovascular autoregulatory and systemic mechanisms contributed to cerebral perfusion recovery during systemic hypotension, and the vasomotor factor was predominant over the cardiac factor. Recovery from cerebral hypoperfusion was slower in the elderly adults because of the age-diminished rates of the CVC response and cardiovascular reflex regulation. Systemic vasoconstriction predominated over increased HR for restoring cerebral perfusion after abrupt onset of systemic hypotension.

Optoacoustic Imaging Offers New Insights into In Vivo Human Skin Vascular Physiology.

Functional imaging with new photoacoustic tomography (PAT) offers improved spatial and temporal resolution quality in in vivo human skin vascular assessments. In the present study, we followed a suprasystolic reactive hyperemia (RH) maneuver with a multi-spectral optoacoustic tomography (MSOT) system. A convenience sample of ten participants, both sexes, mean age of 35.8 ± 13.3 years old, was selected. All procedures were in accordance with the principles of good clinical practice and approved by the institutional ethics committee. Images were obtained at baseline (resting), during occlusion, and immediately after pressure release. Observations of the RH by PAT identified superficial and deeper vascular structures parallel to the skin surface as part of the human skin vascular plexus. Furthermore, PAT revealed that the suprasystolic occlusion impacts both plexus differently, practically obliterating the superficial smaller vessels and evoking stasis at the deeper, larger structures in real-time (live) conditions. This dual effect of RH on the skin plexus has not been explored and is not considered in clinical settings. Thus, RH seems to represent much more than the local microvascular reperfusion as typically described, and PAT offers a vast potential for vascular clinical and preclinical research.

Autoantibody Subtype does not Impact Peripheral Endothelial Function and Hemodynamics in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular dysfunction that leads to vasculopathy and fibrosis. Autoantibody assessment is included as part of the diagnostic criteria and has implications for organ‐involvement and disease. The purpose of this study was to assess peripheral endothelial function and hemodynamics across a range of autoantibody subtypes among patients with SSc. We hypothesized that endothelial function would differ between autoantibody subtypes, with greater dysfunction in the more severe autoantibody subtype (i.e., topoisomerase; SCL70). To our knowledge, this is the first study with an adequate sample size with endothelial function measurements in several autoantibody subtypes. Patients that met ACR/EULAR SSc classification criteria were enrolled at a single center. Endothelial function was assessed in study subjects with the flow‐mediated dilation (FMD) technique using a 5‐min suprasystolic occlusion period and following published guidelines. A blood pressure cuff was placed on the right arm, distal to the ultrasound Doppler probe on the brachial artery. Simultaneous measurements of brachial artery vessel diameter and blood velocity were performed using a linear array transducer operating in duplex mode. The brachial artery was insonated approximately midway between the antecubital and axillary regions, and measurements of diameter and blood velocity were obtained continuously at rest and for 2 minutes after cuff deflation. To determine autoantibody status, patient blood samples were collected, and an antigen‐specific enzyme‐linked immunosorbent assay (ELISA) was performed. One‐way ANOVA was used to determine the variance between groups. Patients with SSc (n=139) were matched for age and disease duration, then grouped by autoantibody status (centromere, topoisomerase, RNA polymerase III, other SSc‐associated autoantibodies, and anti‐nuclear antibody positive, but with no known autoantibody present). In this cohort of patients with SSc, basic clinical characteristics did not differ between autoantibody groups (p>0.05). Baseline brachial artery diameter and blood flow were similar across autoantibody groups (p=0.43 and p=0.82, respectively). Post‐ischemic peak reactive hyperemia and total hyperemia were not different between autoantibody groups (p=0.84 and p=0.99, respectively). There was no difference in absolute % FMD (p=0.11), and this similarity persisted with normalization to the shear rate at peak dilation (p=0.34). We observed no difference in peripheral endothelial function or hemodynamics (i.e., hyperemia and shear) based on autoantibody status. Thus, these data suggest that autoantibody status does not differentially affect peripheral endothelial function and hemodynamics in patients with SSc.Support or Funding InformationFunding Information: Funded in part by NIH R01 AG048366, R01 AG050238, R01 AG060395, K99 AT010017, US Department of Veteran Affairs I01 CX001183

Noninvasive assessment of cardiac output by brachial occlusion-cuff technique: comparison with the open-circuit acetylene washin method.

Cardiac output (CO) assessment as a basic hemodynamic parameter has been of interest in exercise physiology, cardiology, and anesthesiology. Noninvasive techniques available are technically challenging, and thus difficult to use outside of a clinical or laboratory setting. We propose a novel method of noninvasive CO assessment using a single, upper-arm cuff. The method uses the arterial pressure pulse wave signal acquired from the brachial artery during 20-s intervals of suprasystolic occlusion. This method was evaluated in a cohort of 12 healthy individuals (age, 27.7 ± 5.4 yr, 50% men) and compared with an established method for noninvasive CO assessment, the open-circuit acetylene method (OpCirc) at rest, and during low- to moderate-intensity exercise. CO increased from rest to exercise (rest, 7.4 ± 0.8 vs. 7.2 ± 0.8; low, 9.8 ± 1.8 vs. 9.9 ± 2.0; moderate, 14.1 ± 2.8 vs. 14.8 ± 3.2 l/min) as assessed by the cuff-occlusion and OpCirc techniques, respectively. The average error of experimental technique compared with OpCirc was -0.25 ± 1.02 l/min, Pearson's correlation coefficient of 0.96 (rest + exercise), and 0.21 ± 0.42 l/min with Pearson's correlation coefficient of 0.87 (rest only). Bland-Altman analysis demonstrated good agreement between methods (within 95% boundaries); the reproducibility coefficient (RPC) = 0.84 l/min with R2 = 0.75 at rest and RPC = 2 l/min with R2 = 0.92 at rest and during exercise, respectively. In comparison with an established method to quantify CO, the cuff-occlusion method provides similar measures at rest and with light to moderate exercise. Thus, we believe this method has the potential to be used as a new, noninvasive method for assessing CO during exercise.

Regarding the quantification of peripheral microcirculation — Comparing responses evoked in the in vivo human lower limb by postural changes, suprasystolic occlusion and oxygen breathing

The human skin is an interesting model to explore microcirculation, particularly if using noninvasive technologies such as LDF (Laser Doppler Flowmetry) and tc (transcutaneous) gasimetry and methods as near as possible from the normal physiological state. In this study, we combined those technologies with three classical approaches — leg raising from supine, suprasystolic occlusion (in the ankle), and normobaric oxygen breathing to explore distal peripheral circulation in the foot. These methods are often cited, but a comparative assessment has not been done. The goal of this study was to identify relevant flow related descriptors, method-related advantages and pitfalls, and eventually, to find the best experimental approach. Volunteers (both genders, 22.1±3.7years old) were subjected to these methods and variables registered during basal, challenge and stabilization phases. Descriptive and comparative statistics were obtained, adopting a 95% confidence level. All flow-related quantitative descriptors potentially useful for the analysis were identified and compared. As expected, male patients consistently showed higher LDF levels and transepidermal water loss (TEWL) and lower tcpO2 values. However, lower results were recorded in the supine position, suggesting a postural dependence. Both leg raising and suprasystolic occlusion produced a hyperemic response after provocation, although different in magnitude, significantly reducing LDF and tcpO2 during provocation. The oxygen breathing method provided the most patient-friendly protocol, consistently reducing LDF (potentially by the inhibition of production of local vasodilators). TEWL increased during the provocation phase in all protocols, although not significantly. Baseline tcpO2 was found to correlate positively with the peak tcpO2 during oxygen breathing and basal LDF with peak flow during leg raising and suprasystolic occlusion. No statistical correlation between TEWL and LDF could be demonstrated under the current experimental conditions. We conclude that although equally useful considering the purpose, these methods involve very different practicalities and do not provide the same information. Also noteworthy, LDF is a highly sensitive indicator that could be further explored to look deeper into blood flow regulating mechanisms.

Abstract 505: Young Adults With Juvenile Dermatomyositis Have Endothelial Dysfunction: Studies of Brachial Artery Reactivity and Oxidized Lipids

Objective: Older patients with Juvenile Dermatomyositis (JDM) have increased carotid wall thickness and decreased nailfold capillary end row loops (ERL). This study tested young adults with JDM and decreased ERL for brachial artery reactivity (BAR) and HDL antioxidant function. Methods: 20 adults, 14 F, mean age 21.8± 4.2 yrs; mean age at JDM onset 7.6 ± 3.7 years, mean duration of untreated disease (DUD) at diagnosis 5.4 ± 4.8 months, and mean total duration of disease 14.2 ±3.9 years. JDM adults had a mean Total Disease Activity Score (DAS) 1.9 ± 2.5 and were medication free. They were matched by age, race, sex and BMI with 20 healthy controls (mean age 23.8 ± 4.2 years). All subjects were tested for: BAR, ERL number, height and weight. The antioxidant function of HDL was evaluated by the change in fluorescence intensity caused by oxidation of dichlorfluorescein-diacetate by oxidized LDL ±HDL was measured (mean HDL function in healthy controls ranges from 0.44 - 0.66).For BAR, individuals were fasting and rested supine for 10 minutes before ultrasound imaging. Brachial artery diameter was measured at rest and one minute after 4.5 minutes of supra-systolic forearm occlusion. BAR was expressed as the percent diameter change from baseline in response to increased sheer stress [(post-deflation - baseline diameter)/baseline diameter] x100. Results: The # of ERL were significantly lower in the JDM group, 6.35 ± 1.29 vs the controls, 7.4±0.58, p=0.003. The TNF-α -308A allele in the JDM group was 40% vs. 15% in controls. JDM were shorter than their controls, for JDM women, 159.7 ±8.8cm vs. 165.6 ±5.4cm, p=0.048, and for JDM men, 172.7±3.6cm compared to controls, 181.5 ±4.6cm, p=0.0046, perhaps a consequence of steroid administration. BAR in JDM was 3.35±3.06%, and 5.22±3.07% in normal controls (p=0.068). After adjusting for height, age, sex, and BA diameter, the BAR in JDM adults was significantly lower than controls by 2.31% (p=0.04). There were no associations of BAR with ERL, DUD, or DAS or oxidized lipids. Conclusion: BAR is decreased in young adults off medication for JDM, indicating endothelial cell dysfunction. Larger studies in young adults with JDM are needed to validate this finding

Familial hypercholesterolemia affects microvascular autoregulation in children

ObjectiveFamilial hypercholesterolemia (FH) impairs macrovascular endothelial function in childhood and causes an increase of cardiovascular risk in later life. Whether microvascular function is affected in children with FH is unknown. The aim of this study was to investigate the impact of FH on microvascular autoregulation in children by post occlusive reactive hyperemia (PORH). MethodsPORH of the skin was assessed using laser Doppler fluxmetry. Baseline perfusion, biological zero, defined as no-flow laser Doppler signal during suprasystolic occlusion, peak perfusion after release of suprasystolic occlusion, as well as time to peak perfusion and recovery time, defined as time until baseline perfusion is resumed, were measured in 16 children, who were diagnosed with FH according to current guidelines, and in 91 healthy controls. ResultsIn children with FH, peak perfusion was higher (FH: 1.60±0.68 vs. controls: 1.26±0.50AU [arbitrary units], p=0.02), recovery time was longer (110±42.61 vs. 83.18±35.08s, p=0.01) and biological zero was lower than in controls (0.12±0.04 vs. 0.18±0.05AU, p<0.001). Baseline perfusion and time to peak were not different between children with FH and controls (baseline perfusion: 0.43±0.21 vs. 0.38±0.15AU, p=0.18; time to peak: 15.44±12.25 vs. 18.18±17.79s, p=0.56). ConclusionFor the first time the present study reveals an impact of FH on microvascular autoregulation in children: the differences of PORH between children with FH and controls indicate an affected autoregulation of microvascular blood flow in FH, which has its onset in childhood.

Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus

Deterioration of microvascular function may have an early onset in individuals with type 1 diabetes mellitus. We hypothesised that microvascular autoregulation is impaired in children with type 1 diabetes and can be detected non-invasively by postocclusive reactive hyperaemia (PORH). Microvascular autoregulation was assessed in 58 children with type 1 diabetes and 58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry. Baseline perfusion, biological zero (defined as a 'no flow' laser Doppler signal during suprasystolic occlusion), peak perfusion following occlusion, time to peak and recovery time (time until baseline perfusion is resumed) were recorded and compared between the groups. Peak perfusion was higher in children with type 1 diabetes than in healthy controls (1.7 ± 0.93 AU [arbitrary units] vs 1.29 ± 0.46 AU; p = 0.004), and biological zero was lower in children with type 1 diabetes vs controls (0.14 ± 0.04 AU vs 0.19 ± 0.04 AU; p < 0.0001). No differences were seen between the groups in baseline perfusion, time to peak during PORH and recovery time following PORH. PORH reveals impaired microvascular autoregulation in children with type 1 diabetes. The higher peak perfusion might reflect a decline in the vasoconstrictive ability of arteriolar smooth muscle cells upstream of capillary beds in children with type 1 diabetes.

Microvascular function is impaired in children with morbid obesity

Children's obesity is a growing problem in Western societies. We hypothesized that morbid obesity (body mass index [BMI] > 99.5th percentile) might affect microvascular function at an early stage. Therefore, we assessed the microvascular function of 41 obese children (13.2 ± 2.8 years, BMI 32.9 ± 6.6) in comparison to 91 healthy controls (12.7 ± 2.1 years, BMI 18.2 ± 2.5) by post-occlusive reactive hyperemia measured by a laser Doppler: baseline perfusion, biological zero (defined as 'no-flow' laser Doppler signal during supracystolic occlusion), peak perfusion (following occlusion), time to peak perfusion and recovery time (time until resuming baseline perfusion) were recorded and compared between both groups. Peak perfusion was higher in children with morbid obesity than in controls (1.67 ± 0.76 AU [arbitrary units] vs 1.26 ± 0.5 AU, p < 0.001). Consecutively, recovery time was longer in children with morbid obesity (118.21 ± 34.64 seconds) than in healthy children (83.18 ± 35.08 seconds, p < 0.001). In conclusion, higher peak perfusion and prolonged recovery time in children with morbid obesity seem to reflect microvascular dysfunction due to an impaired vasoconstrictive ability of precapillary sphincters.

Maximal exercise, limb ischemia, and endothelial progenitor cells

The concept of neovascularization in response to tissue ischemia was recently extended by the finding of postnatal vasculogenesis through circulating endothelial progenitor cells (EPCs). The aim of this study was to assess the role of acute ischemia for EPC mobilization in patients with peripheral arterial occlusive disease (PAOD) and in healthy volunteers. The number of circulating EPCs was analyzed by flow cytometry in PAOD patients (n = 23) with exercise-induced limb ischemia for up to 72 h after a maximal treadmill test and in healthy volunteers (n = 17) who underwent a 15-min suprasystolic occlusion of one lower extremity to induce limb ischemia. Plasma concentrations of vascular endothelial growth factor, basic fibroblast growth factor, tumor necrosis factor-α, and granulocyte macrophage-colony stimulating factor were determined by ELISA. EPCs (CD 34 pos/KDRpos) increased significantly in both PAOD patients from 82 ± 20 to 256 ± 52 (P < 0.05) and healthy volunteers from 144 ± 39 to 590 ± 61 cells per 1 million events (P < 0.05) in response to induced ischemia, with a maximum after 24 h and returned to baseline within 72 h. The relative increase in EPC numbers was significantly lower in patients with PAOD as compared with healthy volunteers (P < 0.05). Plasma levels of vascular endothelial growth factor increased from 27.4 ± 3.1 to 126.4 ± 12 pg/ml in patients with PAOD (P < 0.05) and from 30.7 ± 6.1 to 134.1 ± 12.4 pg/ml in healthy volunteers (P < 0.05). Both patients with symptomatic PAOD and healthy volunteers respond to a single episode of limb ischemia with a time-dependent increase in circulating EPCs. The increase of EPC numbers in response to ischemia is reduced when vascular disease is present, underlining the reduced vasculogenic potential of patients with PAOD.

The Effect Of Atropine On Cerebral Perfusion During Systemic Hypotension

PURPOSE: The aim of this study was to seek the importance of reflex control of heart rate (HR) in maintaining cerebral perfusion during systemic hypotension. METHODS: Eight healthy subjects (28.4±1.9 yr) gave the written consent to participate in the study that was approved by IRB at UNTHSC. Systemic hypotension was elicited by cuff deflation (CD) following 3-min bilateral supra-systolic occlusion at rest and during lower-body negative pressure (LBNP). RESULTS: Atropine increased baseline HR from 63±2 to 103±3 bpm. However, neither middle cerebral arterial blood flow velocity (VMCA, Doppler) nor mean arterial pressure (MAP, Tonometry) was significantly altered by atropine (before vs after: 66.3±4.0 vs 70.1±4.8 cm/s and 84±4 vs 87±4 mmHg). Though CD elicited hypotension was greater after atropine, the decreases in VMCA were not different (see Table 1). Nonetheless, MAP recovery time following CD was not different before and after atropine despite significant diminution of the tachycardiac response. VMCA recovery time had a trend (P = 0.10) to be longer after atropine.Table 1: Response to cuff deflation after 3-min supra-systolic occlusionCONCLUSION: MAP recovery remained fully compensated after atropine, whereas VMCA recovery was partially dependent on HR reflex.

Abstract 5813: Vascular Function Measured By Digital Thermal Monitoring Strongly Correlates with the Severity of Coronary Artery Disease Diagnosed by 64 Slice Multidetector Computed Tomography

Background: Digital Thermal Monitoring (DTM) of vascular reactivity is a new test of vascular function that correlates well with the Framingham Risk Score and subclinical coronary artery disease measured by the coronary calcium score. This study evaluates whether DTM correlates with the severity of coronary artery disease (CAD) measured by 64 slice multidetector computed tomography (MDCT). Methods: 151 patients, mean age 64±9 years, 69% male, were studied. Each underwent DTM during a 5 minute supra systolic arm-cuff occlusion and MDCT. Post-cuff deflation fingertip temperature rebound (TR) was correlated with CAD severity assessed by MDCT. Results: After adjusting for age, gender and CAD risk factors using logistic regression analysis, the odds ratio for TR in the lowest tertile vs. upper 2 tertiles was 1.3 (95% CI 0.89 –1.6, p=0.4) for mild CAC (luminal stenosis&lt;30%), 2.7 (95% CI 1.2–3.9, p=0.0001) for moderate CAD (30 –70% luminal stenosis) and 6.94 (95% CI 2.2–10.7, p=0.0001) for severe CAD (luminal stenosis&gt;70%) compared to normal coronaries. Additionally, TR was lower in coronary segments with mixed plaque compared to calcified plaque (0.43±0.17 vs. 0.91±0.19, p=0.001). Conclusions: Vascular dysfunction measured by DTM strongly correlates with the severity and characteristics of coronary plaques measured by MDCT, independent of age, gender and cardiac risk factors. DTM may be a useful tool for the identification of high risk patients, additional studies are warranted.

Vascular Reactivity: Evaluation of an acute suprasystolic occlusion with impedance plethysmography

In the clinical set, the evaluation of endothelium- dependent vasodilator response of large vessels is carried out using ultrasound equipment for vascular flow determinations and during administration of vasoactive drugs. This work proposes to use a substantially cheaper technique and a sustained cuff arterial occlusion in order to cause vasodilation. Impedance plethysmography is used to detect the arterial pulse wave over radial artery while the forearm is occluded by above the recording site. From these plethysmographic waves, three indexes and their changes -between control and maximal response post-occlusion- were calculated. 33 complete records obtained from healthy low-risk volunteers were analyzed. Between control and post-occlusion maximal response, "average percentual change of pulse wave amplitude" were (35±13)%, "stiffness index" did not show significant differences (6,38±0,98 vs 6,38±0,94 and "reflection index" was significant lower (58±15 vs 35±16)%. These results indicate that: 1- cuff occlusion maneuver was effective to cause endothelium-dependent vasodilation, 2-changes of pulse wave amplitude and reflection index could be used as markers of athero-arteriosclerotic damage in the vascular bed, even in sub-clinical conditions.

Abnormal microvascular response is localized to the digits in patients with systemic sclerosis

To investigate the hypothesis that cutaneous microvascular perfusion of the dorsum of the hand (in response to local heating) and distal phalanx (in response to occlusion) is impaired in patients with systemic sclerosis (SSc) compared with healthy controls. Twenty-nine patients with SSc and 29 control subjects were recruited. Perfusion was monitored using novel dual-wavelength laser Doppler imaging, allowing measurement of both smaller (capillaries) and larger (thermoregulatory) vessels. Postacclimatization, a baseline dorsum scan (red or green wavelength) was performed. A heating pad was placed on the dorsum (total stimulus time 6 minutes at 34-40 degrees C), and following removal of the pad, baseline wavelength scans were performed until perfusion returned to baseline values. This was then repeated for the second wavelength. The maximum perfusion increase due to heating (PEAK1) and area under the perfusion-time curve (AUC) were determined. In addition, scans (both wavelengths) of the index finger were performed prior to and during 2 minutes of suprasystolic occlusion, and the response upon occlusion release was monitored with single-point laser Doppler. The decrease in perfusion due to occlusion (from preocclusion baseline values) (%DECREASE) and the maximum increase (from baseline perfusion values under occlusion) in hyperemic perfusion upon removal of occlusion (PEAK/OCC) were calculated. PEAK1 and AUC values were not significantly different between patients and controls, as assessed with either wavelength. A significant difference between groups was found in the %DECREASE values with the green, but not the red, wavelength. A significant between-group difference was also found in PEAK/OCC values, using both wavelengths. This study suggests that SSc has no effect on microvascular perfusion in the dorsum of the hand, and that the abnormal microvascular response is localized to the digits, affecting both smaller and larger vessels.

INVITED COMMENTARY

Coronary artery bypass grafting (CABG) with saphenous vein conduits is one of the most commonly performed surgical procedures worldwide. Unfortunately, saphenous vein graft patency is only 50% at 10 years. As a result, there has been a growing interest in the use of arterial conduits, particularly the radial artery (RA), as excellent midterm patency results of more than 90% have been reported. Nevertheless, concerns have been raised about decreased blood flow to the hand with potential morbidity after RA harvesting. This paper by Knobloch and colleagues describes a novel combined laser-Doppler flowmeter system that can be used to measure palmar microcirculation in attempts to avoid ischemic complications of the hand. Palmar circulation was evaluated using the laser-Doppler flowmeter before and 2 days after RA harvesting. Patients were tested for either complete suprasystolic occlusion of the brachial artery or alternate occlusion of the radial and ulnar arteries. As expected, changes in both blood flow and tissue oxygenation saturation decreased with various occlusive maneuvers. After RA harvest, tissue flows and saturations were the same as for the nondonor hand. This “proof-of-concept” study is small with only 15 patients, all of whom were less than 60 years of age. One wonders how well this system would work in the elderly, smoking, or diabetic population with small vessel occlusive disease. By including more patients and then applying a subgroup analysis, the authors might have answered this question. The Allen test is simple and safe, and is performed commonly to assess palmar circulation. Unfortunately, the authors make no mention of whether concomitant Allen testing was performed in any of these patients. Furthermore, there are no comparative results or descriptions of how the device might be more reliable than the Allen test. Correlation with the laser-Doppler flowmeter system would have been interesting and would have validated the utility. Nevertheless, one of the more interesting points of the paper was that despite reduction in palmar blood flow and tissue oxygen saturation with RA harvesting, 2 days postoperatively both tissue oxygen saturation and blood flow were not reduced compared with the other hand and, more importantly, compared with preoperative values. Potential mechanisms might include increased compensatory blood flow from the remaining artery or the opening of small collaterals within the palmar arch hand. This finding raises a critical point in the use of this new technology. Should decreases in blood flow and tissue oxygen saturation be disregarded as they return to baseline 2 days after RA harvest, or is there some dangerous threshold before RA harvesting that can be detected by this new method? In summary, further work will need to include a wider patient population to determine whether this technology can add more clinical information for patients whose RA is harvested. Moreover, will this device predict and detect who may have postoperative ischemic complications? This important question must be answered before surgeons can conclude that the laser-Doppler flowmeter will add functional information that goes beyond the Allen test.

Low-dose atropine amplifies cardiac vagal modulation and increases dynamic baroreflex function in humans

It has been previously known that low-dose atropine (LDA) enhances vagal outflow to the heart. To demonstrate the importance of vagal cardiac modulation in arterial blood pressure (ABP) stability, we evaluated the effect of vagal cardiac stimulation with administration of LDA on ABP fluctuation during dynamic hypertensive and hypotensive stimuli. We assessed changes in RR interval (RRI), ABP, power spectral densities of heart rate variability (HRV) and ABP variability, and spontaneous baroreflex sensitivity (BRS) in 16 healthy volunteers before and after administration of LDA (2 μg/kg). Transient hypertension was induced by phenylephrine (2 μg/kg), whereas hypotension was induced by bilateral thigh cuff deflation after a 3-min suprasystolic occlusion. LDA elicited bradycardia and significantly increased high-frequency (HF, 0.15–0.4 Hz) power of HRV and spontaneous BRS, as determined by transfer function analysis. The increase in systolic blood pressure (SBP) after phenylephrine administration was significantly attenuated by LDA (16±2 to 11±3 mmHg, P<0.005) and was associated with the augmented reflex bradycardia, whereas the decrease in SBP after cuff deflation was not affected (14±5 to 13±5 mmHg) with the augmented reflex tachycardia. Increases of HF HRV were correlated significantly and negatively with the increased SBP induced by phenylephrine before and after LDA ( r=−0.502, P<0.05). These data suggest that the increased vagal cardiac function induced by LDA augments HR buffering effects, and is important in minimizing arterial pressure fluctuation during dynamic hypertensive stimuli.

The cutaneous uptake of atmospheric oxygen contributes significantly to the oxygen supply of human dermis and epidermis.

It has been known since 1851 that atmospheric oxygen is taken up by the human epidermis. The contribution to total respiration is negligible. Until now the significance for the local oxygen supply of the skin has remained unknown. With a newly developed sensor, the oxygen fluxoptode, it has become possible to make local measurements of the transcutaneous oxygen flux (tcJ(O2)). In this study the sensor was calibrated so that absolute values of tcJ(O2) could be reported. At rest, tcJ(O2) was determined on normal, humidified skin on the volar forearm of 20 volunteers of different age groups. In order to evaluate the contribution of the blood flow to the oxygen supply of the skin, tcJ(O2) was recorded at the end of a 5 min suprasystolic occlusion of the forearm. At normal skin surface partial oxygen pressure (163 +/- 9 Torr), tcJ(O2) was 0.53 +/- 0.27 ml O2 min(-1) x m(-2). A 5 min interruption of blood flow resulted in an increase of 9.5 +/- 6.3 % in tcJ(O2). The value of tcJ(O2) was unaffected by the age of the subject. Published data on the oxygen diffusion properties of skin and simulations of intracutaneous profiles of oxygen partial pressure indicated that under these conditions, the upper skin layers to a depth of of 0.25-0.40 mm are almost exclusively supplied by external oxygen, whereas the oxygen transport of the blood has a minor influence. As a consequence, a malfunction in capillary oxygen transport cannot be the initiator of the development of superficial skin defects such as those observed in chronic venous incompetence and peripheral arterial occlusive disease.

The Transepidermal Oxygen Flux from the Environment is in Balance with the Capillary Oxygen Supply

It has been known since the nineteenth century that oxygen is taken up by the human skin. With a newly developed sensor it became possible to examine the influence of the vascular supply on the oxygen flux into the skin, tcJ(O2). tcJ(O2) was measured optically by determining the oxygen partial pressure difference, DeltapO2 across a diffusion test membrane, which itself was brought into close contact to the skin surface. Under these conditions DeltapO2 is proportional to the tcJ(O2). The skin perfusion was varied by the application of a hyperemizing ointment on the abdomen of 12 volunteers and by suprasystolic occlusion at the thigh of 20 volunteers. The tcJ(O2) was measured at a temperature of 33 degrees C of the humid skin. It was compared with the skin perfusion monitored by laser Doppler flow, and the capillary oxygen supply measured by transcutaneous partial pressure of oxygen, tcpO2, at an electrode temperature of 37 degrees C. The transcutaneous O2 flux produced a distinct DeltapO2 of 81.8 +/- 8.2 Torr (abdomen) and 72.8 +/- 12.3 Torr (ankle). In hyperemic skin on the abdomen the O2 flux was reduced (DeltapO2 = 57.7 +/- 10.6 Torr). The tcpO2 increased from 8.7 +/- 10.7 to 35.1 +/- 16.9 Torr. During suprasystolic occlusion, DeltapO2 increased by 6.4 +/- 2.3 Torr, whereas laser Doppler flow and tcpO2 decreased significantly. These results indicate that the total oxygen supply of the epidermis and the upper dermis is guaranteed even if the perfusion varies.

Local Oxygen Content in the Skin Is Increased in Chronic Venous Incompetence

In skin lesions of chronic venous incompetence (CVI) transcutaneous oxygen pressure (tcpO2) at the ankle is often reduced. However, in some CVI patients the tcpO2 during suprasystolic occlusion remains significantly higher than in healthy subjects. The aim of the present study was to investigate which kind of CVI patients develop this phenomenon and whether the higher tcpO2 during occlusion is caused by a smaller oxygen consumption of the skin or by an increased local oxygen content. The oxygen consumption of the skin was measured by the pO2 decrease (ΔtcpO2/Δt) after stopping the arterial oxygen supply when the hemoglobin was saturated by oxygen inhalation, i.e., at tcpO2 values above 120–130 mmHg. By multiplying the tcpO2 with the mean oxygen solubility coefficient of the skin the content of physically dissolved oxygen is obtained. The decrease of tcpO2 in the 55- to 45-mmHg range indicates the consumption of oxygen physically dissolved and chemically bound to hemoglobin. It gave a parameter for estimating the local hemoglobin content of the skin. These values and the minimal tcpO2 after a 5-min arterial occlusion were measured in 14 healthy subjects, in 13 patients with varicose veins, but no skin lesions, in 10 patients with CVI lesions like white atrophy and lipodermatosclerosis and in 16 CVI patients with open venous ulcers. During suprasystolic occlusion tcpO2 at the ankle remained significantly higher in CVI patients with skin lesions than in the healthy control subjects (25.6 ± 18.9 versus 8.0 ± 7.0 mmHg). The steepness of the tcpO2 decrease caused by cutaneous oxygen consumption in healthy subjects was not significantly different from the CVI patients. In contrast, the decrease of tcpO2 at the ankle between 55 and 45 mmHg was 1.9 ± 2.0 mmHg/s in the control group and 0.7 ± 0.5 mmHg/s in the group with open venous ulcers. These results indicate a higher hemoglobin content in the skin of the CVI patients than in healthy subjects. Obviously, the hemoglobin bound oxygen content in the skin of CVI patients is increased. Thus, a lack of oxygen is unlikely to be the primary reason for the development of skin lesions in CVI.

The post‐occlusive hyperemic response in patients with systemic sclerosis

We investigated post-ischemic hyperreactive cutaneous blood flow in patients with primary Raynaud's phenomenon and Raynaud's phenomenon secondary to systemic sclerosis (SSc). Reactive hyperemia was measured over a locally warmed area of skin, using a laser Doppler flowmeter, following 5 minutes of suprasystolic occlusion of blood flow. We found that patients with primary Raynaud's phenomenon had normal post-ischemic blood flow compared with normal controls. In contrast, patients with SSc had reduced levels of baseline and peak blood flow compared with either the primary Raynaud's phenomenon patients or the normal subjects. Infusion of carbaprostacyclin, a potent prostacyclin analog vasodilator, did not increase blood flow in the SSc patients, nor did it restore the reactive hyperemic response. These findings are consistent with the hypothesis that patients with the nonvasoconstricted condition of SSc have fixed structural defects that limit cutaneous microvascular blood flow.