Laser Doppler Imaging Scanning Research Articles

Assessing antibacterial efficacy of a polyhexanide hydrogel versus alginate-based wound dressing in burns.

Burn injuries pose a heightened risk of infection, which is primarily responsible for increased morbidity and mortality. Factors such as extensive skin damage and compromised immunity exacerbate this vulnerability. Pseudomonas aeruginosa and Staphylococcus aureus are frequently identified in burns, with Gram-negative Pseudomonas aeruginosa often resistant to antibacterial agents. While Flaminal, an alginate-based wound dressing (Flen Health, Belgium), aids wound healing, its antibacterial effects are limited compared with 1% silver sulfadiazine (1% SSD). In contrast, Prontosan Wound Gel X, a betaine and polyhexanide-based hydrogel (B. Braun Medical AG, Switzerland), has been shown to effectively combat various microbes and promotes wound healing. In this study, two research cohorts were retrospectively established (control group: patients receiving standard of care with the alginate-based wound dressing; intervention group: patients receiving the polyhexanide hydrogel wound dressing), comprising patients admitted to a burn centre between 2019 and 2022. Patients were eligible when continuous wound treatment with either of the two wound dressings was performed. Laser Doppler imaging (LDI) scans were conducted. Regions of interest (ROIs) were selected based on LDI scans and divided into healing time categories. Wound swabs were collected and the presence of Pseudomonas aeruginosa and Staphylococcus aureus was documented. Bacterial load was evaluated using a semiquantitative scale. Wound healing was recorded. The control group consisted of 31 patients with 93 ROIs, while the intervention group had 67 ROIs involving 29 patients. Both groups exhibited similar proportions of healing time categories (p>0.05). The polyhexanide hydrogel dressing outperformed the alginate-based dressing in antiseptic efficacy by significantly reducing the incidence of Pseudomonas aeruginosa- and Staphylococcus aureus-positive cultures in patients' wounds. Wound healing time for conservative treatment was comparable between groups. In this study, the polyhexanide hydrogel dressing minimised Pseudomonas aeruginosa and Staphylococcus aureus colonisation in burn wounds, demonstrating strong antibacterial properties, emphasising its potential to minimise infections in burn injuries.

Validity of thermography for measuring burn wound healing potential.

Accurate assessment of burn wound depth and the associated healing potential is vital in determining the need for surgical treatment in burns. Infrared thermography measures the temperature of the burn wound noninvasively, thereby providing indirect information on its blood flow. Previous research demonstrated that a small, low‐priced, handheld thermal imager has an excellent reliability, but a moderate validity for measuring burn wound healing potential. A new and more sensitive version of this convenient device has become available. The aim of this study was to evaluate the validity of thermography for measuring burn wound healing potential, compared to Laser Doppler Imaging (LDI) as a reference standard. Thermal images and LDI scans were obtained from burn wounds between 2 and 5 days postburn. Temperature differences between burned and nonburned skin (ΔT) were calculated. To evaluate validity, ΔT values were compared to the healing potential categories assessed by LDI. Two receiver operating characteristic curves were created and two ΔT cutoff values were calculated to illustrate the ability to discriminate between burn wounds that heal in a time period of less than 14 days, between 14 and 21 days, and more than 21 days. Between June and October 2018, 43 burn wounds in 32 patients were measured. ΔT cutoff values of 0.6°C (sensitivity 68%, specificity 95%) and −2.3°C (sensitivity 30%, specificity 95%) were calculated to discriminate between burn wounds that heal in <14 and ≥14 days, and burn wound that heal in ≤21 and >21 days, respectively. This study shows a good validity of the feasible thermal imager for the assessment of burn wound healing potential. Therefore, we consider it a promising technique to be used for triage in local hospitals and general practices, and as a valuable addition to clinical evaluation in burn centers.

Laser Doppler imaging as a tool in the burn wound treatment protocol.

IntroductionThe main treatment of burns is early excision of injured tissues.AimTo compare two different methods of examination of burned patients: clinical burn depth examination (CDE) and laser Doppler imaging (LDI).Material and methodsA prospective randomized study of 57 burn patients treated in 2009–2011 was carried out. The burned patients were randomized into a CDE group and an LDI group. The CDE and LDI scan were performed 72 h after injury, with the second and third CDE and LDI scan on the 7th and 14th day after the burn. Age, sex, length of inpatient stay, cost of burn treatment, burn depth, cause and localization of the burns were analyzed between the two groups.ResultsFifty-seven patients were treated during 2 years. Thirty-two patients were in the CDE group and 25 patients were in the LDI group. Most of the patients were male (45 male vs. 12 female, p < 0.001). The age was similar between the males and the females (female: 46.4 ±16.9 years vs. male: 46.3 ±12.5 years; p = 0.11). The mean length of stay in hospital was significantly higher in the CDE group (47 ±34.4 day vs. 25 ±10.8 day; p = 0.005). The mean cost of treatment of burned patients was significantly higher in the CDE group.ConclusionsThe length of stay and cost of treatment of burn patients depends upon early diagnosis of the deep burns and well-timed surgical treatment of burn wounds.

Skin Perfusion of Fingers Shows a Negative Correlation with Capillaroscopic Damage in Patients with Systemic Sclerosis

To the Editor: Two variants of laser Doppler monitoring exist to evaluate digital blood flow: laser Doppler imaging (LDI) and laser Doppler flowmetry (LDF). The first technique uses a scanning method with a distant light source and detector, while the second uses optical fibers to carry the light to and from the tissue. As a result, LDF measures the microcirculatory blood flow through a very small volume of tissue, whereas LDI scans a larger tissue area. LDF continuously measures skin blood perfusion; because of the scanning time, LDI cannot measure it continuously1. We address the relationship between digital blood flow and capillaroscopic damage in patients with systemic sclerosis (SSc). Table 1 outlines the main studies. View this table: Table 1. Main studies of laser Doppler monitoring and capillaroscopy to evaluate microvascular damage in patients with systemic sclerosis (SSc). Using LDI, Correa, et al found lower digital blood flow in 44 patients with SSc compared with healthy controls at baseline and after cold stimulus2. No correlation was found between functional … Address correspondence to Prof. Salsano; E-mail: felice.salsano{at}uniroma1.it

Friction Burns in Children

Laser Doppler imaging (LDI) has been increasingly used to predict pediatric burn wound outcome. A majority of these wounds are scald, contact, or flame burns. No study has specifically evaluated the use of LDI in pediatric friction burns. Our objective was to critically evaluate LDI assessment of pediatric friction burns to determine its predictive value with this mechanism of injury. We conducted a retrospective review of all LDI scans performed on pediatric friction burns during a 2-year period. We identified 36 patients with a mean age of 3.6 years (range, 19 months to 15 years). LDI accurately predicted burn wound outcome in 23 (64%) cases. In 13 cases, LDI did not correctly predict burn wound outcome. Eight were expected to heal within 14 days, but six of those eight took an average of 20.3 days to heal (range, 18-29 days), and the other two required skin grafting. Of the remaining five incorrect predictions, four were caused by an inability to correlate the flux scan with the clinical appearance of the burn, and one was thought to take more than 21 days to heal but healed within this period. Our data suggest that LDI appears to be a less reliable tool in predicting the outcome of friction burns when compared to other mechanisms of burn injury in children. This may reflect the physical differences in the mechanism of friction burns as opposed to other forms of thermal injury.

Burn wound healing time assessed by laser Doppler imaging (LDI). Part 1: Derivation of a dedicated colour code for image interpretation

IntroductionLaser Doppler imaging produces a colour-coded image of dermal blood flow, which can be used to quantify the inflammatory response in a burn. The original colour palette had arbitrary boundaries, which inexperienced clinicians found difficult to interpret. The aim of this study was to define clinically useful boundaries that would assist in the prediction of burn healing potential. MethodWe conducted a prospective, multi-centre study of burns in adults and children. LDI scans were performed between 48h and 5 days after injury. The burns were assessed clinically and photographed on day of scan, day 14 and day 21 post-injury. Areas healed at day 14, healed between day 14 and 21 and unhealed at day 21 were identified on the LDI scan. The flow values for the pixels in these regions were analysed to calculate boundaries between the three healing categories. ResultsWe recruited 137 patients (ages 1–88 years, 65% male); 392 LDI scans contained 433 different burn sites; 109 regions of interest were studied. Analysis allowed us to define ranges for the three healing categories: HP14 colour coded red, >600PU; HP14–21, yellow, 260–440PU; HP>21, blue, <200PU; separated by two overlap regions pink, 440–600PU and green, 200–260PU. Blue was subdivided to show the very high association between LDI<140PU and non-healing at day 21. ConclusionWe have devised a new colour palette for LDI burn imaging based on healing times of a series of burns. Validation of this palette is described separately, in Part 2.

A Functional Murine Model of Hindlimb Demand Ischemia

To date, murine models of treadmill exercise have been used to study general exercise physiology and angiogenesis in ischemic hindlimbs. The purpose of these experiments was to develop a murine model of demand ischemia in an ischemic limb to mimic claudication in humans. The primary goal was to determine whether treadmill exercise reflected a hemodynamic picture which might be consistent with the hyperemic response observed in humans. Aged hypercholesterolemic ApoE null mice (ApoE(-/-), n = 13) were subjected to femoral artery ligation (FAL) and allowed to recover from the acute ischemic response. Peripheral perfusion of the hindlimbs at rest was determined by serial evaluation using laser Doppler imaging (LDI) on days 0, 7, and 14 following FAL. During the experiments, mice were also assessed on an established five-point clinical ischemic score, which assessed the degree of digital amputation, necrosis, and cyanosis compared to the nonischemic contralateral limb. After stabilization of the LDI ratio (ischemic limb flux/contralateral nonischemic limb flux) and clinical ischemic score, mice underwent 2 days of treadmill training (10 min at 10 m/min, incline of 10 degrees ) followed by 60 min of daily treadmill exercise (13 m/min, incline of 10 degrees ) through day 25. An evaluation of preexercise and postexercise perfusion using LDI was performed on two separate occasions following the onset of daily exercise. During the immediate 15 min postexercise evaluation, LDI scanning was obtained in quadruplicate, to allow identification of peak flux ratios. Statistical analysis included unpaired t-tests and analysis of variance. After FAL, the LDI flux ratio reached a nadir between days 1 and 2, then stabilized by day 14 and remained stable through day 25. The clinical ischemic score stabilized at day 7 and remained stable throughout the rest of the experiment. Based on stabilization of both the clinical ischemic score and LDI ratio, exercise training began on day 15. The peak 15 min postexercise LDI ratio increased significantly compared to the preexercise ratio on day 17 (0.48 +/- 0.04 vs. 0.34 +/- 0.04, p < 0.05) and day 25 (0.37 +/- 0.03 vs. 0.27 +/- 0.03, p < 0.01). Within 2 hr of exercise, the LDI ratio returned to preexercise levels on both days 17 and 25. Clinical and hemodynamic stabilization of limb perfusion is evident by 14 days after FAL. FAL followed by demand ischemia results in a reversible relative hyperemic response similar to that observed in exercising human claudicants. A murine model of FAL associated with demand ischemia may be useful to evaluate the metabolic, inflammatory, and flow-related changes associated with claudication in humans.

The Impact of Laser Doppler Imaging on Time to Grafting Decisions in Pediatric Burns

Early definitive treatment of burns facilitates optimal results by reducing the risk of subsequent hypertrophic scarring. Laser Doppler imaging (LDI) has been shown to assist in predicting burn wound healing potential. This study sought to determine whether use of LDI in pediatric burn patients has led to earlier decision making for grafting. The study cohort were patients who underwent a skin grafting procedure for a burn wound at a single institution, a state referral center for all major pediatric burns, between June 2006 and December 2007. Patients were divided into two groups: those who underwent LDI scanning and those who were only assessed clinically. Time of burn injury to time of decision making for the grafting procedure was calculated in days. Forty-nine percent of 196 patients underwent LDI. The mean time from the date of injury to decision making for graft procedure was 8.9 days in those patients who had an LDI scan vs 11.6 days in the group assessed by clinical observation alone. This trend for earlier decision for grafting procedure in the LDI group was statistically significant (P = .01). There was no significant difference between those patients who were scanned and those only assessed clinically in relation to gender, age, mechanism of injury, percentage BSA burnt, and wound culture results. There was a significant reduction in time to grafting decision in the LDI group. This would potentially lead to reduced length of stay, reduced number of hospital visits, and streamlined care for the patient and their family.

Laser Doppler Imaging of Genital Blood Flow: A Direct Measure of Female Sexual Arousal

Female sexual arousal is a challenging construct to measure, partly because of the subtle nature of its indicators, vaginal lubrication and genital swelling. As a result, many instruments have been used in an attempt to accurately measure it; however, problems are associated with each. Furthermore, the relationship between subjective and physiological indicators of arousal appears to be influenced by the instrument used to measure physiological arousal. Specifically, instruments measuring physiological arousal internally yield lower correlations between measures of physiological and subjective arousal than instruments examining the external genitals. Laser Doppler imaging (LDI) is a direct measure of external genital blood flow. The purpose of this study was to investigate the usefulness of LDI for measuring genital blood flow in women in response to erotic visual stimuli, and to explore the relationship between physiological and subjective sexual arousal. Sixty-five participants watched three 15-minute films during LDI scanning. Two nature films (measuring acclimatization and baseline blood flow levels) and one randomly assigned experimental film (erotic, anxiety, humor, or neutral) were used. Participants rated their level of subjective arousal following the third film. Results indicated a significant effect of film condition on genital blood flow, P < 0.001, with the erotic condition differing significantly from the other three conditions. In terms of the relationship between physiological and subjective sexual arousal, physiological arousal was significantly predicted by subjective ratings of sexual arousal (P < 0.001). LDI appears to be able to differentiate blood flow during erotic and nonerotic conditions. In addition, physiological sexual arousal was significantly predicted by women's reported subjective sexual arousal. These findings suggest that LDI is a useful instrument for measuring female sexual arousal, and that women may be more aware of their level of physiological arousal than previously assumed.

Accuracy of early burn depth assessment by laser Doppler imaging on different days post burn

Background Accurate diagnosis of burn depth is essential in selecting the most appropriate treatment. Early assessment of burn depth by clinical means only has been shown to be inaccurate, resulting in unnecessary operations or delay of grafting procedures. Laser Doppler imaging (LDI) was reported as an objective technique to determine the depth of a burn wound, but the accuracy on very early days post burn has never been investigated yet. Methods In 40 patients with intermediate depth burns, we prospectively evaluated and compared the accuracy of the LDI measurements with the clinical assessments on days 0, 1, 3, 5, 8. Clinical evaluation of the depth of the burn was performed by two observers blinded to the LDI images. Accuracies were assessed by comparison with outcome: healing times longer than 21 days were considered to be equivalent to a biopsy finding of a deep dermal wound. Obviously superficial and full thickness wounds were excluded. LDI flux level was used for LDI prediction of outcome: less than 220 PU to predict non-healing at day 21. Results The accuracies of burn depth assessments on the day of burn and post burn days 0, 1, 3, 5 and 8 using LDI were 54%, 79.5%, 95%, 97% and 100% compared with clinical assessment accuracies of 40.6%, 61.5%, 52.5%, 71.4% and 100%, respectively. LDI accuracy was significantly higher than clinical accuracy on day 3 ( p < 0.001) and day 5 ( p = 0.005). Burn depth conversion was also considered. This is the first study to quantify the advantage of LDI scanning over clinical assessments during these important early after burn days.

Microvascular responses following digital thermal hyperaemia and iontophoresis measured by laser Doppler imaging in idiopathic inflammatory myopathy

To measure microvascular function using laser Doppler imaging following digital hyperaemia and iontophoresis of vasoactive substances in patients with idiopathic inflammatory myopathy (IIM). Fifteen patients with IIM including eight patients with dermatomyositis (DM) and seven patients with polymyositis (PM) were studied. Fifteen age-matched normal controls were also recruited. Scanning red laser Doppler imaging (LDI) was performed after resting the subject in a temperature controlled room at 23 degrees C for 20 min. An initial LDI scan was performed to assess baseline blood flow. Digital microvascular responses were quantified following a maximum hyperaemic response (MHR) and iontophoresis with endothelial dependent acetylcholine (Ach) and endothelial independent sodium nitroprusside (SNP). Maximum vasodilation following iontophoresis was expressed as a percentage of the MHR. All subjects were age matched, and the duration of disease was similar between the IIM patients. There was no significant difference in baseline blood flow when comparing the three study groups. There was no significant difference in MHR or SNP/MHR when comparing DM or PM with controls. However, Ach/MHR was significantly lower in both the DM and PM group compared with controls (both P < 0.01). There was no significant difference in any of the microvascular responses when comparing patients with DM directly with PM. This is the first study to evaluate microvascular responses using LDI in patients with IIM. We have demonstrated that patients with DM have abnormal endothelial dependent mediated vasodilation and the same abnormality is present in patients with PM.

Maximum blood flow and microvascular regulatory responses in systemic sclerosis

Objectives. To investigate microvascular function using laser Doppler imaging (LDI) following response to hyperaemia, neurovascular reflex and iontophoresis in systemic sclerosis (SSc) in comparison with primary Raynaud's phenomenon (PRP) and age-matched controls. A secondary aim was to evaluate if SSc patients with a higher Medsger vascular score have lower endothelial responses. Methods. Twenty patients with SSc, 10 PRP and 17 controls were studied. Patients with SSc were scored using the vascular component of the Medsger severity scale. A baseline LDI scan was performed on the dorsal aspect of both hands. Digital responses were quantified following maximum hyperaemic response (MHR), contralateral vasoconstrictor response (CLVc) and iontophoresis with acetylcholine (Ach)-endothelial dependent and sodium nitroprusside (SNP)-endothelial independent. Mean blood flow was quantified over a standard region of interest. Results. MHR was lower in SSc patients compared with controls (P < 0.001). A similar trend was seen when comparing SSc with PRP although this did not reach significance (P = 0.07). CLVc and Ach/MHR were lower in SSc vs PRP (P < 0.05) and controls (P < 0.001). No difference was observed in MHR, CLVc and Ach/MHR between PRP and controls. Overall, SNP/MHR was similar in all the three groups. SSc patients with a higher Medsger vascular score had lower endothelial-dependent (P < 0.01) and independent (P < 0.05) responses. Conclusion. SSc patients have abnormal microvascular regulatory responses compared with PRP and controls. This study also suggests that the degree of endothelial dysfunction may be related to the degree of peripheral vascular involvement.

Repetitive Ischemia–Reperfusion Injury: A Plausible Mechanism for Documented Clinical Burn-Depth Progression After Thermal Injury

Our previous studies confirmed the phenomenon of burn depth progression despite adequate Parkland formula resuscitation [Kim et al. J Burn Care Rehabil 2001;22960:406-6]. Repetitive ischemia-reperfusion injury (I-R) is a plausible explanation and is suggested by the concomitant swings we have observed in serum base deficit (BD) during resuscitation from burn shock. We chose to explore whether laser Doppler imaging (LDI) evidence of burn depth progression mirrored cycles of I-R (episodic swings in continuously measured BD). Positive findings would support the hypothesis that repetitive episodes of I-R is a factor in burn depth progression despite apparently adequate resuscitation. A total of 14 patients with severe life-threatening burns (median 51% TBSA) underwent continuous BD monitoring using a Paratrend 7 (Malvern PA) during 48 hours of resuscitation. Fluid needs were estimated using the Parkland formula, then were titrated to urine output. The slopes of BD changes were then analyzed. Worsening of BD greater than 0.2 mmol/l/min was noted, and a proportion derived relative to pooled data on 5-minute intervals. In four of the patients, LDI scans were performed on six representative areas sequentially every 4 hours. The analysis of median flux in these LDI images provided real-time determination of burn depth progression. Eight patients eventually died. Only four patients achieved a normal BD within 12 hours of monitoring despite exceeding the Parkland formula estimate and meeting urinary output parameters. Our analysis also showed cyclical peaks and valleys in the BD curve (P < .001), suggesting repetitive I-R insults. All increases in BD preceded changes that could be detected in vital signs or urine output. Finally, LDI confirmed that the burn depths continued to progress despite apparently adequate resuscitation, and also showed that there are similar peaks and valleys in the perfusion of the wounds (P < .0001), which mimic the changes in the BD curve. Responses to fluid resuscitation do not follow a linear pattern in the case of massive burns. These results in repetitive periods of tissue hypoperfusion evidenced by BD alterations and may contribute to progressive deepening of the burn wound.

Intensive care requirements in paediatric burns revisited

This study sought to assess the validity of independent, blinded reporting of Laser Doppler Imaging (LDI) prediction of burn wound outcome in children. Two experienced paediatric burn consultants were invited to report on LDI scans performed routinely within 3 days of burn. They were provided with the LDI flux image, a low-resolution colour digital photograph of the burnt area and a basic history. Report predictions were correlated with outcome. Reports were compiled on 50 scans performed on 31 patients at a mean of 54 h post burn. Of the 100 reports generated, mean correlation with outcome was 97%. If the LDI predicted a deep burn, it was always correct. Non-correlations were due to a number of factors including inadequate scanning of the affected area, excessive movement and residual wound debris. Accurate prediction of burn wound outcome could be made via the standard information generated by LDI and appeared more reliable than clinical prediction. The correlation improved with increasing experience with LDI.

Laser Doppler Imaging of paediatric burns: Burn wound outcome can be predicted independent of clinical examination

This study sought to assess the validity of independent, blinded reporting of Laser Doppler Imaging (LDI) prediction of burn wound outcome in children. Two experienced paediatric burn consultants were invited to report on LDI scans performed routinely within 3 days of burn. They were provided with the LDI flux image, a low-resolution colour digital photograph of the burnt area and a basic history. Report predictions were correlated with outcome. Reports were compiled on 50 scans performed on 31 patients at a mean of 54 h post burn. Of the 100 reports generated, mean correlation with outcome was 97%. If the LDI predicted a deep burn, it was always correct. Non-correlations were due to a number of factors including inadequate scanning of the affected area, excessive movement and residual wound debris. Accurate prediction of burn wound outcome could be made via the standard information generated by LDI and appeared more reliable than clinical prediction. The correlation improved with increasing experience with LDI.

Kidney oxygenation during water diuresis and endothelial function in patients with type 2 diabetes and subjects at risk to develop diabetes

The aim of the present study was to examine the relationship among water diuresis-induced changes in renal oxygenation, endothelial function, and various metabolic parameters in type 2 diabetic patients and healthy subjects at risk of type 2 diabetes. Thirty-eight subjects with type 2 diabetes (D: age, 54 ± 10 years, mean ± SD, 24 men) and 7 healthy subjects with parental history of type 2 diabetes or with impaired glucose tolerance (IGT) (relatives [R]: age 46 ± 11 years, 4 men) were included. Laser Doppler imaging scanning was used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (Ach) and 1% sodium nitroprusside (SNP), and ultrasound was used to measure the flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) in the brachial artery. Renal oxygenation was assessed by magnetic resonance imaging (MRI) before and during water diuresis. A decrease in the magnetic parameter R2∗ implies an increase in oxygenation. Renal medullary oxygenation did not improve with diuresis in either group (D: −0.5 ± 1.9, R: −0.4 ± 2.1, P = not significant [NS]). The renal cortical oxygenation showed a small, but statistically significant, improvement after diuresis in the 2 groups (D: −0.6 ± 1.1, R: −0.5 ± 0.5, P < .05). There were no correlations between the change in cortical R2∗ (R2∗ post-minus R2∗ prewater diuresis) and the micro- and macrovascular reactivity. The postdiuresis renal cortical R2∗ was negatively correlated with both the Ach- and SNP-induced skin vasodilation (% change over baseline)( r = −.40, P < .01 and r = − .39, P < .05, respectively), while no correlation existed with the FMD and NID. The baseline renal cortical oxygenation was also negatively correlated with the SNP-induced skin vasodilation ( r = −.36, P < .05) and positively correlated with the fasting plasma glucose, total cholesterol, and vascular cell adhesion molecule (VCAM) concentrations ( r = .34, P < .05, r = .31, P < .05 and r = .37, P < .05, respectively). These preliminary findings suggest an association between the kidney cortical oxygenation and the skin microvascular reactivity, glycemia, and lipidemia. Water diuresis failed to produce an improvement in renal medullary oxygenation in both patients with diabetes and subjects at risk for diabetes.

No alpha-adrenoreceptor-induced C-fiber activation in healthy human skin.

In healthy volunteers, flare responses induced by norepinephrine (NE) iontophoresis have been observed. However, as NE iontophoresis is a combined electrical and chemical stimulus axon, reflexes cannot be directly linked to pharmocological activity of NE. Different concentrations of NE, clonidine (CL), and phenylephrine (PE) (NE: 10(-10)-10(-3) M; CL and PE: 10(-8)-10(-3) M) were applied via intradermal microdialysis fibers into the skin of healthy volunteers. Simultaneously, skin blood flow was visualized by laser-Doppler imaging scans and quantified in a vasoconstriction skin area directly above the membranes to control drug effects and in expected axon reflex vasodilation areas that were 0.75 cm apart. NE, PE, and CL caused dose-dependent vasoconstriction. However, neither in the presumed axon reflex areas (quantitative analysis) nor on laser-Doppler imaging pictures (qualitative analysis) were any vasodilation observed. Even at concentrations causing maximum vasoconstriction (10(-3) M for any drug), no vasodilation was induced. Our results indicate that, in healthy human skin, exogenously supplied alpha-adrenoreceptor agonists alone do not activate nociceptors sufficiently to induce axon reflex flare.

Pathophysiological basis of acute inflammatory hyperaemia in the rat knee: roles of cyclo-oxygenase-1 and -2.

The role of different isoforms of cyclo-oxygenase (COX) in mediating the acute (0-6 h) and late (24 h) phases of inflammation was investigated in the rat knee joint following intra-articular injection of carrageenan. The hyperaemic response was assessed transcutaneously using laser Doppler imaging (LDI). Samples were taken at corresponding time points for detection of synovial COX-1, COX-2 and inducible nitric oxide synthase (iNOS) mRNA, and measurement of urinary prostaglandin (PG) and nitric oxide metabolites (NO(x)). A non-selective COX inhibitor (indomethacin, 15 mg kg(-1) I.P.), a selective COX-2 inhibitor (SC-236, 16.8 mg kg(-1) I.P.) or vehicle were administered 1 h prior to carrageenan in the acute phase study. LDI scans were taken hourly for 4 h post-induction. Inflammatory hyperaemia in the vehicle group was attenuated in the indomethacin- (P < 0.001, two-way ANOVA) and SC-236-treated groups (P < 0.0001), with no difference between these treatments. At 24 h, I.V. infusion of indomethacin (0.1 mg min(-1)), increased vascular resistance (24 +/- 7.1 %; P < 0.05) compared to vehicle infusion, whereas SC-236 (0.11 mg min(-1)) did not. Resistance changes to indomethacin also differed from SC-236 (P < 0.05). Knee joint diameter progressively increased over 24 h (P < 0.0001, one-way ANOVA). Urinary PG levels increased by 6 h (P < 0.05), but returned to baseline by 24 h. COX-1 mRNA was detectable at all time points; COX-2 mRNA only at 3 h. Urinary NO(x) levels increased progressively over 24 h (P < 0.05), paralleled by induction of iNOS in the 3 and 24 h samples. Prostaglandin production via COX-2 appears to mediate the development of acute inflammatory hyperaemia, but nitrergic mechanisms may supervene subsequently. COX-1 but not COX-2 contributes to the maintenance of basal blood flow in the hyperaemic joint at 24 h.

Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria.

Using von Willebrand Factor (vWF) as a marker of endothelial function, previous studies have shown that the development of microalbuminuria is associated with the onset of endothelial dysfunction in individuals with type 2 diabetes. We tested the hypothesis that endothelial dysfunction is already evident in normoalbuminuric individuals with type 2 diabetes. We used laser Doppler imaging scanning to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). Multiple indicators of endothelial function--soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM), vWF, and microvascular reactivity--were measured in 20 healthy control subjects, 45 normoalbuminuric (urinary albumin/creatinine ratio < 30 micrograms/mg) individuals with type 2 diabetes, and 14 microalbuminuric (urinary albumin/creatinine ratio between 30 and 300 micrograms/mg) individuals with type 2 diabetes. Serum sICAM and sVCAM levels were elevated in the normoalbuminuric (305 +/- 120, 851 +/- 284 ng/ml) and microalbuminuric (300 +/- 89, 845 +/- 252 ng/ml) individuals with diabetes when compared with the healthy control subjects (213 +/- 58, 661 +/- 176 ng/ml) (P < 0.01). Furthermore, the microvascular endothelium-dependent and -independent vasodilation was reduced in the normoalbuminuric (76 +/- 44, 70 +/- 33) (percent increase in perfusion over baseline) and microalbuminuric (74 +/- 41, 73 +/- 28) individuals with diabetes compared with healthy control subjects (126 +/- 67, 120 +/- 47) (P < 0.05). In contrast, plasma vWF was elevated only in the microalbuminuric individuals with diabetes (129 +/- 35%) compared with the normoalbuminuric individuals with diabetes (110 +/- 34) and healthy control subjects (111.3 +/- 39) (P < 0.05). On stepwise multivariate analysis, fasting blood glucose was the most important contributing factor to the variation in microvascular reactivity and sVCAM, whereas insulin resistance (by homeostasis model assessment) was the most important contributing factor to the variation in sICAM. Addition of all clinical and biochemical measures explained only 15-22% of the variation in sICAM, sVCAM, and microvascular reactivity. Multiple markers of endothelial dysfunction were evident in normoalbuminuric individuals with type 2 diabetes. The pathogenic process of vasculopathy in type 2 diabetes occurs early and may be operative before the development of microalbuminuria.