Dermal Perfusion Research Articles

FRI606 Changes In The Pedal Microcirculation Of Diabetic Patients With Poor Glycemic Control Detected Using Non Invasive Optical Imaging

Abstract Disclosure: I.K. Bolakale-Rufai: None. S. French: None. J.C. Arias: None. K. Concha-Moore: None. T. Tan: None. D.G. Armstrong: None. A. Mazhar: Employee; Self; Modulim. C.C. Weinkauf: None. Background: Microvascular disease (MVD) describes systemic changes in the small vessels (∼100 υm diameter) that impair tissue oxygenation and perfusion. Emerging evidence has shown that MVD (which is prevalent in diabetics) is clinically relevant as it synergistically acts with peripheral arterial disease to increase the risk of limb loss by 22.7-fold. Poor glycemic control has been linked to clinical microvascular disease (nephropathy and retinopathy) However, the direct impact of poor glycemic control on the microcirculation of the feet is unknown as there are currently no standardized non-invasive methods used clinically to assess and quantify MVD of the lower limbs. Spatial frequency domain imaging (SFDI) is a novel non-invasive optical technology that can detect and quantify microvascular disease of the foot by measuring the amount of hemoglobin(HbT1) in the capillaries of the superficial dermis up to 1-2mm deep and oxygenation (StO2) in the dermal micro-circulation. We hypothesize that poor glycemic control in DM affects pedal microcirculation and the changes can be detected using the SFDI technology. Methods: 307 patients (600 lower extremity limbs) were prospectively enrolled at a single institution, Banner University Medicine, Tucson, AZ from 2016- 2023. Diabetic patients were stratified into three groups based on their HbA1c level: ≤6.7%, 6.8-9.9%, and ≥10%. Mann U Whitney test and Spearman rank correlation were used in testing the association between HbA1C and SFDI-metrics with p<.05 considered as statistical significance. Results: We included 230 lower limbs belonging to diabetic patients. The mean age of the patients was 61.7 years. Clinical neuropathy and retinopathy were found in 79% and 30.7% of patients, respectively. SFDI-derived biomarkers of microcirculation were compared among diabetics categorized by HbA1C levels. We observed a significant reduction in papillary dermal perfusion (HbT1) as the glycemic control (HbA1C) of the patients worsened (p<0.001). Although tissue oxygenation (StO2) was not statistically different across diabetic groups, the St02/HbT1 ratio which represents the ratio of tissue oxygenation to perfusion, increased with elevated HbA1C levels. This indicated that poorly controlled diabetics had less oxygen being extracted from their poorly perfused micro-circulation. Conclusions: This study suggests that poor glycemic control directly affects the microcirculation of the feet in diabetic patients. The SFDI technology is a promising noninvasive tool to evaluate microvascular disease of the feet and potentially may be utilized clinically to stratify diabetic patients at risk for foot ulceration or limb loss based on glycemic control over time. Presentation: Friday, June 16, 2023

Optimizing Transcutaneous Oxygen Measurement Sites on Humans.

This study utilizes an optical method of transcutaneous oxygen sensing that has the potential to revolutionize at-home care. This technique is based on quenching the luminescence of a platinum porphyrin film. Since oxygen quenches luminescence, its lifetime is further measured to assess the partial pressure of transcutaneous oxygen diffusing through the skin. Unlike conventional transcutaneous oxygen monitors that use electrochemical sensors, the luminescence-based sensor allows the use of dry electrodes that do not require heating and reduce the risk of accidental skin irritations or burns. These properties not only improve patient safety but also allow the creation of miniature wearable transcutaneous oxygen sensors for continuous and accurate remote respiratory monitoring. To this end, it is critical to assess the efficiency of the wearable sensor by determining the optimal location for its placement on the body. Depending on the location on the body, physiological factors such as blood flow rate and skin thickness affect dermal perfusion of transcutaneous oxygen. In this work, four healthy volunteers participated in subject testing. We assessed each participant at the following locations: thumb, top of the wrist, forearm, thigh, and shin. All locations consistently reported accurate and reliable data. Among them, the thumb demonstrated shorter settling times and the most uniform luminescence lifetime values.

The Iatrogenic Injury Potential of Self-adherent, Elastic Bandages in Finger Injuries.

The use of a self-adherent, elastic bandage is a practical way to dress finger injuries. Multiple reports describe iatrogenic injuries from elastic bandages, ranging from skin necrosis to finger gangrene, necessitating amputations. This study investigated whether elastic bandages can compromise digital perfusion by occluding arterial blood flow in healthy volunteers and evaluated the utility of pulse oximetry as a monitoring tool for digital perfusion. A technique for safe bandage application is proposed. A commercially available elastic bandage was wrapped around the index finger of 20 healthy volunteers at varying degrees of stretch. Digital perfusion measurements were carried out using photoelectric pulse transduction, laser Doppler flowmetry, and pulse oximetry. Intracompartmental pressure measurements were recorded using a separate in vitro experimental model. Elastic bandages applied at maximum stretch did not change digital brachial index or pulse oximetry values, suggesting arterial blood flow was preserved distal to the bandage. Intracompartmental pressure measurements at maximum stretch remained below the systolic digital pressure. In contrast, superficial dermal perfusion fell to 32% of normal as measured by laser Doppler flow, at 100% bandage stretch. This study suggests a risk for iatrogenic injury when using elastic bandages for finger dressings. While arterial inflow was never compromised, pressures were high enough to occlude superficial venous outflow, which may begin at 20% bandage stretch. Pulse oximetry failed to detect changes distal to applied dressings, and we do not recommend it to detect digital vascular compromise in this setting.

Dermal Nipple-Areola Complex Perfusion through Circumareolar Scars: A Delay Model in Two-Stage Nipple-Sparing Mastectomy.

Nipple-sparing mastectomy (NSM) has evolved as a standard surgical option. The NSM complication rate remains high in large breasts. To reduce the risk of necrosis, several authors have proposed delayed procedures to enhance blood supply to the nipple-areola complex (NAC). The purpose of this study in a porcine model was to show adequate redirection of NAC perfusion by neoangiogenesis through circumareolar scars. Delayed two-staged NSM was simulated in 52 nipples (six pigs) with a 60-day interval. The nipples underwent a full-thickness, circumareolar incision onto the muscular fascia, with preservation of underlying glandular perforators. After 60 days, NSM was performed through a radial incision. A silicone sheet was introduced in the mastectomy plane to prevent NAC revascularization by wound bed imbibition. Digital color imaging was used to assess necrosis. Near-infrared fluorescence with indocyanine green was used to assess perfusion patterns and perfusion in real time. No NAC necrosis was seen after 60 days' delay in any nipples. In all nipples, indocyanine green angiography showed complete alteration of the NAC vascular perfusion pattern from subjacent gland to a capillary fill following devascularization, exhibiting a predominant arteriolar capillary blush without distinct larger vessels. NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days' delay. Identical staged delay in humans may be a surgically safe NSM option and could broaden therapeutic NSM indications in difficult breasts. Large clinical trials are necessary to provide identical results in human breasts. NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days of delay. Identical staged delay in humans may be a surgically safe NSM option.

Establishment of Safety of Hemostatic Net Application Utilizing Laser Assisted Fluorescence Angiography with SPY-Q Software Analysis.

The hemostatic net, which was initially described as a method to decrease hematoma rates in face/neck lift procedures, has since increased in practice and applicability. However, despite its demonstrated safety and efficacy, there exists significant skepticism with regards to its necessity; in particular, there is concern that the transcutaneous sutures may restrict dermal perfusion. The goal of this study was to assess flap perfusion, both pre- and post- the application of the hemostatic net, to determine if there is an objective decrease in tissue perfusion in relation to application of the hemostatic net, as measured by laser-assisted angiography (LAA). Eight patients underwent cervicofacial flap reconstruction of cutaneous malignancy defects, after which a hemostatic net was applied. All patients underwent evaluation with LAA both pre- and post- the application of the net. The average relative and absolute perfusion of different zones of the flap were calculated. The average absolute change in relative perfusion was +6.41%, +0.31%, and +3.28% for zones 1, 2, and 3, respectively, after application of the hemostatic net. There was no statistical difference in relative tissue perfusion after application of the net. There were no instances of delayed healing, infections, ischemia, necrosis, or hematoma. One patient developed a seroma after the net was removed. No patients had scarring or residual track marks from the transcutaneous sutures. With the use of LAA, we were able to objectively demonstrate no significant decrease in tissue perfusion after the application of the hemostatic net.

Noninvasive assessment of foot perfusion in cholesterol-fed rabbits using dynamic volume perfusion CT with an upslope method

To evaluate the feasibility of dynamic foot volume CT with the upslope method and to demonstrate macrovascular reactivity and microvascular perfusion during cuff-induced reactive hyperemia state in cholesterol-fed rabbits. 30 New Zealand male rabbits were divided into 2 groups: dietary hypercholesterolemia (n = 10) and normal diet control (n = 20). To measure for macrovascular reactivity, perfusion parameters of the left posterior tibial artery was measured at baseline and at reactive hyperemia state. For the evaluation of microvascular perfusion, color-coded perfusion map of the plantar dermis was generated for perfusion CT scan by an in-house developed dedicated analysis software based on upslope method. Dermal perfusion values were measured and analyzed before and after cuff-induced reactive hyperemia. Foot dynamic volume CT with the upslope method demonstrated significant impairment of both macrovascular reactivity and microvascular perfusion in cholesterol-fed rabbits without significant macrovascular lesions during cuff-induced reactive hyperemia (CRH) state. Arterial time-to-peak of cholesterol-fed rabbits failed to show acceleration while chow-fed rabbits showed significant decrease in time. Microvascular perfusion calculated by perfusion value (P < 0.01) and perfusion ratio (P = .014) showed decreased microvascular perfusion in cholesterol-fed rabbits compared to chow-fed rabbits during CRH state. Post-CT pathologic examination revealed decreased endothelial cell density in cholesterol-fed rabbits (P < 0.001). Foot perfusion CT using upslope method provides perfusion parameters for large arteries and a perfusion map of the foot during cuff-induced reactive hyperemia in cholesterol-fed rabbits. It may be a useful tool to assess microvascular reactivity in patients with peripheral artery disease but no apparent macrovascular lesions.

Assessing the impact of aging and blood pressure on dermal microvasculature by reactive hyperemia optical coherence tomography angiography

Visualization and quantification of the skin microvasculature are important for studying the health of the human microcirculation. We correlated structural and pathophysiological changes of the dermal capillary-level microvasculature with age and blood pressure by using the reactive hyperemia optical coherence tomography angiography (RH-OCT-A) technique and evaluated both conventional OCT-A and the RH-OCT-A method as non-invasive imaging alternatives to histopathology. This observational pilot study acquired OCT-A and RH-OCT-A images of the dermal microvasculature of 13 young and 12 old healthy Caucasian female subjects. Two skin biopsies were collected per subject for histological analysis. The dermal microvasculature in OCT-A, RH-OCT-A, and histological images were automatically quantified and significant indications of vessel rarefaction in both old subjects and subjects with high blood pressure were observed by RH-OCT-A and histopathology. We showed that an increase in dermal microvasculature perfusion in response to reactive hyperemia was significantly lower in high blood pressure subjects compared to normal blood pressure subjects (117% vs. 229%). These results demonstrate that RH-OCT-A imaging holds functional information of the microvasculature with respect to physiological factors such as age and blood pressure that may help to monitor early disease progression and assess overall vascular health. Additionally, our results suggest that RH-OCT-A images may serve as a non-invasive alternative to histopathology for vascular analysis.

Laser Doppler Perfusion Imaging in the Mouse Hindlimb.

Blood flow recovery is a critical outcome measure after experimental hindlimb ischemia or ischemia-reperfusion. Laser Doppler perfusion imaging (LDPI) is a common, noninvasive, repeatable method for assessing blood flow recovery. The technique calculates overall blood flow in the sampled tissue from the Doppler shift in frequency caused when a laser hits moving red blood cells. Measurements are expressed in arbitrary perfusion units, so the contralateral non-intervened upon leg is usually used to help control measurements. Measurement depth is in the range of 0.3-1 mm; for hindlimb ischemia, this means that dermal perfusion is assessed. Dermal perfusion is dependent on several factors-most importantly skin temperature and anesthetic agent, which must be carefully controlled to result in reliable readings. Furthermore, hair and skin pigmentation can alter the ability of the laser to either reach or penetrate to the dermis. This article demonstrates the technique of LDPI in the mouse hindlimb.

Transcutaneous oximetry: variability in normal values for the upper and lower limb.

Published normal transcutaneous oxygen partial pressures (PtcO2) for the chest and lower limb have defined tissue hypoxia as a value of < 40 mmHg (< 30 mmHg in some patients, < 50 mmHg in others). To determine 'normal' PtcO2 for the upper and lower limb in healthy, non-smoking adults using the Radiometer® TCM400 with tc Sensor E5250. Thirty-two volunteers had transcutaneous oxygen measurements (TCOM) performed on the chest, upper and lower limbs breathing air, with leg then arm elevated and whilst breathing 100% oxygen. Room-air PtcO2 (mmHg, mean (95% confidence interval)) were: chest: 53.6 (48.7-58.5); upper arm: 60.0 (56.1-64.0); forearm: 52.3 (44.8-55.8); dorsum of hand: 50.2 (46.1-54.3); thenar eminence: 70.8 (67.7-73.8); hypothenar eminence: 77.9 (75.1-80.7); lateral leg: 50.2 (46.2-54.2); lateral malleolus: 50.5 (46.6-54.3); medial malleolus: 48.9 (45.6-52.1); dorsum, between first and second toe: 53.1 (49.2-57.0); dorsum, proximal to fifth toe: 58.5 (55.0 - -62.0); plantar, 1st MTP: 73.7 (70.3-77.1). Nineteen subjects had at least one room-air PtcO2 below 40 mmHg (nine upper limb, 13 lower limb, four chest). Approximately 10% lower limb PtcO2 were < 100 mmHg on normobaric oxygen. Only one subject at one site had an upper limb PtcO2 < 100 mmHg breathing oxygen. The broad dispersion in PtcO2 in our healthy cohort reflects the inherent biologic variability in dermal perfusion and oxygen delivery, making it difficult to define narrow, rigid 'normal' values. Thus, we cannot recommend a single PtcO2 value as 'normal' for the upper or lower limb. A thorough patient assessment is essential to establish appropriateness for hyperbaric oxygen therapy, with TCOM used as an aid to guide this decision and not as an absolute.

Reducing Wound Tension with Undermining or Imbrication—Do They Work?

Background:For the noncolonized wound, achieving tension-free, primary wound closure is ideal. Some surgeons advocate imbrication of deeper tissues rather than undermining, posing that imbrication preserves more dermal perfusion while still reducing tension at the wound edge. We sought to determine which technique most reliably reduced wound tension while preserving dermal wound perfusion.Methods:A total of 5 standardized, symmetrical pairs of full thickness wounds were created on Duroc swine. Wound tension was measured with a Tyrolean tensiometer before and after either method of closure, whereas a speckle contrast imager was used to assess dermal edge perfusion. Skin tension and dermal perfusion were evaluated for statistical significance via paired t tests and a multivariate analysis of variance.Results:There was a significant reduction in wound tension with undermining and imbrication relative to the raw wound tension (5 and 5.9 vs 7.1 N; P < 0.05) yet no significant difference between methods of closure (P > 0.05). There was a significant reduction in dermal perfusion between unwounded skin and the imbricated wound (222 perfusion units [PU] vs 48 PU; P < 0.05) and between the unwounded skin and the undermined wound (205 vs 63 PU; P < 0.05).Conclusions:We found no significant difference in wound tension between wound undermining or imbrication and a significant decrease in dermal perfusion after imbrication and undermining although the relative decrease in perfusion was greater with imbrication. Wound undermining reduces skin tension with greater relative dermal perfusion to the skin and should be selected over wound imbrication in standard primary wound closure.

Detection and analysis of temperature-sensitive dermal blood perfusion dynamics and distribution by a hybrid camera system.

In this paper we present an application of two optical imaging modalities for non-invasive assessment of dermal perfusion. This hybrid setup consists of a photo-plethysmographic camera sensing in the visible spectrum and a thermal camera sensing in the infrared-C-band. This allows to combine the information of both sources complementarily: The extracted perfusion index as well as the skin surface temperature. The feasibility of the presented system is tested in two studies with local temperature stress on the forehead of a subject. In the first, a local cooling on the subject's forehead is monitored and further analyzed. In the second, skin perfusion reactions to heat are considered. For both experiments the results are compared to baseline measurements and non-affected areas in the field of view of the cameras. As results, the dependencies between temperature and perfusion change are presented. Further, influences of the stressor can be visualized in functional mappings of calculated perfusion indices. For the performed test, a linear correlation between temperature and perfusion change is obtained.

Cost-effectiveness of laser Doppler imaging in burn care in the Netherlands

BackgroundEarly accurate assessment of burn depth is important to determine the optimal treatment of burns. The method most used to determine burn depth is clinical assessment, which is the least expensive, but not the most accurate.Laser Doppler imaging (LDI) is a technique with which a more accurate (>95%) estimate of burn depth can be made by measuring the dermal perfusion. The actual effect on therapeutic decisions, clinical outcomes and the costs of the introduction of this device, however, are unknown. Before we decide to implement LDI in Dutch burn care, a study on the effectiveness and cost-effectiveness of LDI is necessary.Methods/designA multicenter randomised controlled trial will be conducted in the Dutch burn centres: Beverwijk, Groningen and Rotterdam. All patients treated as outpatient or admitted to a burn centre within 5 days post burn, with burns of indeterminate depth (burns not obviously superficial or full thickness) and a total body surface area burned of ≤ 20% are eligible. A total of 200 patients will be included. Burn depth will be diagnosed by both clinical assessment and laser Doppler imaging between 2–5 days post burn in all patients. Subsequently, patients are randomly divided in two groups: ‘new diagnostic strategy’ versus ‘current diagnostic strategy’. The results of the LDI-scan will only be provided to the treating clinician in the ‘new diagnostic strategy’ group. The main endpoint is the effect of LDI on wound healing time.In addition we measure: a) the effect of LDI on other patient outcomes (quality of life, scar quality), b) the effect of LDI on diagnostic and therapeutic decisions, and c) the effect of LDI on total (medical and non-medical) costs and cost-effectiveness.DiscussionThis trial will contribute to our current knowledge on the use of LDI in burn care and will provide evidence on its cost-effectiveness.Trial registrationNCT01489540

Microcirculation Perfusion Monitor on the Back of the Health Volunteers

Objective. To observe the dermal microcirculation blood perfusion characterization of meridians channels (acupoints). Methods. 20 healthy human subjects were monitored using Pericam Perfusion Speckle Imager (PSI) for the changes in dermal microcirculation blood perfusion on governor meridian and other respective dermal regions as a control. Result. The microcirculation blood perfusion on Governor Meridian is higher than its control area. Conclusion. The dermal microcirculation blood perfusion on certain parts of Governor Meridian of healthy human subjects showed specifics.

LOP01

INTRODUCTION: Multidetector computed tomography (MDCT) angiography is “the gold standard” for preoperative perforator selection. DIRT is based on the relationship between dermal perfusion and the change in rate and pattern of skin rewarming following a cold challenge. Can DIRT be an alternative to MDCT? METHODS AND MATERIALS: 23 patients scheduled for breast reconstruction with DIEP flap were included. Preoperatively arterial perforator sounds were located with a hand held Doppler. Afterwards a desktop fan was used to deliver a mild cold challenge to the lower abdomen. The rate and pattern of rewarming of the skin was registered with an infrared camera. The locations of first appearing hot spots on the skin were registered. Eight patients had an additional MDCT scan. RESULTS: A rapid appearing “hot spot” was associated with an arterial Doppler sound and a suitable perforator intraoperatively. All DIEP flaps survived and were based on the perforator as selected from DIRT. The selected hot spot could easily be related to a perforator on the MDCT scan. CONCLUSION: Perforator selection of DIEP flaps is facilitated with the use of DIRT. The technique is non-invasive, provides real-time information and does not require exposure to ionizing radiation or intravenous contrast medium. DIRT could be an alternative for MDCT in perforator selection.

New Insights in the Phenomenon of Distributed Dermal Perfusion Rhythmicity using Computer Aided Optoelectronic Sensor Measuring Strategies

In recent years optoelectronic sensor concepts have gained an important role in medical diagnosis because of their non-invasive nature. They are generally accepted by the patients since they don't cause pain and are devoid of harmful radiation or ionising phenomena. One method which is nowadays an accepted and widely used diagnosis technique for assessment of skin perfusion is Photoplethysmography (PPG). It assesses the optical attenuation of the skin, which is modulated by the time varying blood contents. This non-invasive technique allows acquiring functional data from the arterial and/or venous system. However the classical PPG sensors, which consist of a LED as light source and a photodiode as detector, need skin contact for the measurements and can only assess a single spot of a few square millimetres. Advancement to classical PPG is camera based Photoplethysmography-Imaging Method (PPGI), which is not only non-invasive but can assess dermal perfusion completely without skin contact and also delivers spatially resolved measurements.

Tissue perfusion measurements: multiple-exposure laser speckle analysis generates laser Doppler–like spectra

Variations in skin perfusion are easily detected by laser speckle contrast maps, but a robust interpretation of the information has been lacking. We show that multiple-exposure laser speckle methods produce the same spectral information as laser Doppler methods when applied to targets with embedded moving scatterers. This enables laser speckle measurements to be interpreted more quantitatively. We do this by using computer simulation of speckle data, and by experimental measurements on Brownian motion and skin perfusion using a laser Doppler system and a multiple-exposure laser speckle system. The power spectral density measurements of the light fluctuations derived using both techniques are exactly equivalent. Dermal perfusion can therefore be measured by laser Doppler or laser speckle contrast methods. In particular, multiexposure laser speckle can be rapidly processed to generate a full-field map of the perfusion index proportional to the concentration and mean velocity of red blood cells.

Effect of aspirin on random pattern flap survival in rats

Aspirin is known to increase dermal perfusion and is commonly used to enhance anastomotic patency in microvascular surgery. However, we were unable to find any reports of an effect of aspirin on simple flap survival. In order to determine its effect on flap survival, a controlled experiment was designed using random pattern flaps in rats. The results indicate a statistically significant increase in flap survival in rats receiving aspirin. It is suggested that aspirin’s anti-aggregation effect, in combination with its vasodilatational and anti-inflammatory effect, increases the perfusion in the initial critical hours and thus secondarily decreases the reperfusion injury.

Topical local anaesthetics (EMLA ®) inhibit burn-induced plasma extravasation as measured by digital image colour analysis

Amide local anaesthetics have previously been shown to reduce oedema and improve dermal perfusion following experimental burns. Previous studies have used invasive techniques for burn oedema quantification which do not allow continuous monitoring in the same animal. The present study used digital image colour analysis to investigate the effect of topical local anaesthetics on burn-induced extravasation of Evans blue albumin. A standardised full-thickness burn injury (1 × 1 cm) was induced in the abdominal skin of anaesthetised rats. The burn area was subsequently covered with 0.5 g of lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA ®, ASTRA, Sweden) or placebo cream during the first hour post-burn. One hour after the burn trauma, animals received Evans blue dye intravenously. Skin colour appearances were recorded by macrophotography before the burn and 5, 60, 65, 90, 120, 150, and 180 min post-burn. Colour slides were digitised and colour changes were analysed using the normalised red-green-blue ( n-rgb) colour system. Results showed a significant inhibition of Evans blue extravasation between 60 and 180 min post-burn in EMLA ®-treated animals versus controls. Topical local anaesthetics are potent inhibitors of burn-induced plasma albumin extravasation, probably by direct action on vascular permeability and by inhibition of various steps of the pathophysiological response after burn injury.

Increased dermal perfusion after skin burn injury by d- myo-inositol-1,2,6-trisphosphate

Full-thickness burn injury results in a continuous deterioration of blood flow due to vascular sludging, thrombosis formation and oedema leading to irreversible ischaemia and tissue necrosis, d- myo-inositol-1,2,6-trisphosphate (IP 3) has previously been shown to reduce burn-induced oedema formation and inflammation involved in the pathophysiology of progressive ischaemia. A full-thickness burn injury (1 cm 2) was induced in the abdominal skin of anaesthetized rats using an electrically heated thermoprobe. Blood flow in the experimental area was measured by laser Doppler flowmetry during 6.5 h postburn. The experiments included five groups. Three burned groups were treated intravenously with IP 3 and received respectively: a bolus dose of 4 mg/kg followed by a continuous intravenous infusion of 20 mg/kg/h, 8 mg/kg + 40 mg/kg/h or 16 mg/kg + 60 mg/kg/h. One burned and one unburned control group received a corresponding bolus dose and infusion of saline. Results showed a significant inhibition of dermal ischaemia in the burned groups receiving IP 3 at all dose intervals as compared to saline-treated burned rats (all P < 0.001). We conclude that IP 3 improved local dermal perfusion in burned skin. Probable mechanisms of action could be the vasodilatory and anti-inflammatory properties of the agent.

What is the transport-limiting barrier in iontophoresis?

We document evidence that the major rate-limiting step in iontophoretic drug delivery of low molecular weight charged solutes can be dermal perfusion at the site of application; for high molecular weight solutes, on the other hand, transport to the site of microcirculation uptake may, in some circumstances, become the slowest step.