Use of Laser Doppler Imaging to Assess Microvascular Response to Thermal Stress

Evaluating Lower Limb Ischemia Use of Laser Doppler Imaging to Assess Microvascular Response to Thermal Stress

Dixie R. Aragaki, MD, Min-Ning Huang, MD, PhD, Peggy Chen, MD, Peter Yeung, MD, Charles Kunkel, MD, Dorene Opava-Rutter, MD, A.M. Erika Scremin, MD, and Oscar U. Scremin, MD, PhD

Assessment of cutaneous microvascular perfusion can provide important clues about wound and amputation healing in patients with diabetes. These investigators examined the practicality of laser Doppler imaging in this setting.

iabetes is a major public traumatic amputation in the United venules that is not readily studied by health problem, especially States, and the disease has resulted routine ultrasonic Doppler imaging in the VA, whose patient in about 80,000 lower extremity am- or ankle-brachial index calculations. Dpopulation has a substan- putations per year since 1997.2 Three In the past, methods of estimating tially higher prevalence of the disease years after a diabetes-related lower skin perfusion included radioiso- (11.4%) compared with the general extremity amputation, the mortal- tope studies to record skin perfusion U.S. population (7.2%).1 Among ity rate is between 35% and 50%.3 pressure10 or tissue tracer uptake,11 the many complications of diabe- Furthermore, since proximal am- segmental systolic blood pressure,10 tes, lower extremity amputation is putation levels demand higher en- arteriography,12 and capillary micros- particularly distressing. Diabetes is ergy expenditure to ambulate with a copy.13 These methods are time con- currently the leading cause of non- prosthesis,4 patients who’ve had such suming, however, and have varying amputations face limited mobility degrees of reproducibility.14 In 2000, Dr. Aragaki is the assistant program director for and independence. This high cost to the Transatlantic Inter-Society Con- the physical medicine and rehabilitation (PM&R) individual health and functioning is sensus identified transcutaneous PO residency program at the Greater Los Angeles 2 VA Healthcare System (GLAVAHS) and an assis- sadly matched by the immense finan- (TcPO2) measurement, radionuclide 5 tant clinical professor in the department of medi- cial cost of associated health care. In scans, laser Doppler methods, and cine at the University of California, Los Angeles 2003, diabetes-related lower extrem- capillary microscopy as useful ad- (UCLA) David Geffen School of Medicine, both in Los Angeles, CA. Dr. Huang, Dr. Chen, and Dr. ity amputations accounted for ap- juncts in assessing critical limb isch- 2 15 Yeung are all practicing physiatrists who, at the proximately 810,000 hospital days. emia. In recent years, TcPO2 and time of this study, were PM&R residents at the Given the scope of this problem, laser Doppler methods have become GLAVAHS. Dr. Kunkel is the assistant chief of PM&R services at the GLAVAHS and an associate there is an urgent need to further our widely used to assess skin microper- 16 professor in the department of medicine at UCLA understanding of the pathophysiology fusion and oxygenation. David Geffen School of Medicine. Dr. Opava- leading to amputations in the diabetic Laser Doppler flowmetry (LDF), Rutter is the director of PM&R polytrauma at the 6–8 GLAVAHS. Dr. A. Scremin is the chief of PM&R population. Microvascular function which can monitor skin blood flow services at the GLAVAHS and a professor and the of the skin—which is important to in real time over a small area, has chair of the PM&R division of the department of wound healing, hemostasis, tempera- been used in many areas of medicine, medicine at UCLA David Geffen School of Medi- 17 cine. Dr. O. Scremin is a rehabilitation research ture regulation, and immune system including plastic surgery, vascular 18 19 and development senior research career scientist modulation—has emerged as a physi- medicine, burn management, and in the department of research at the GLAVAHS ologic variable of interest.9 dermatology.20 Additionally, some and a professor emeritus in the department of physiology at the UCLA David Geffen School of The cutaneous vasculature is a fine investigators have reported its util- Medicine. network of arterioles, capillaries, and ity in assessing amputation level and

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wound healing in diabetic and non- mal and abnormal LDI values and to was approved by the VA Greater Los diabetic patients.18,21 LDF used in characterize the physiologic nature Angeles Institutional Review Board. conjunction with thermal stressing of the thermal response. To that end, (application of controlled heat) has we analyzed the microvascular re- Procedure revealed significantly lower perfusion sponse to thermal stress, as measured Participants were placed prone on in amputees than in control partici- by scanning LDI, on three cutaneous a hospital bed. Pillows were placed pants,22 and it has resulted in better calf sites of healthy individuals and strategically to offer comfort and clinical correlation with ischemia se- individuals with peripheral vascular minimize movement artifacts. Skin

verity than either TcPO2 or Doppler disease and diabetes mellitus (PVD- temperature was measured with an ankle pressure measurement.23 DM). Specific aims were to identify infrared thermometer at each test site Scanning laser Doppler imaging useful microperfusion parameters that before skin heating. Circular probes (LDI) is a more recently developed can distinguish between people with that were 19 mm in diameter and technique that provides advantages and without PVD-DM and to charac- contained at their centers a heating over the LDF device—primarily the terize the spatial and temporal course element 8 mm in diameter (Transcu-

ability to produce a relatively large, of heat-induced microvascular hyper- taneous CO2/O2 Monitor, Novametrix two-dimensional image with superior emic response in normal skin. Medical Systems Inc., Wallingford, spatial resolution24 and temporal re- CT) were applied with a 7-mm wide producibility25,26 without direct skin METHODS adhesive tape ribbon, concentric and contact. LDI achieves this by using external to the probe border. a continuous raster scanning laser Participants Probes were placed posteriorly beam across the skin surface. Dop- For the study, we enrolled 12 healthy at approximately 10 cm (proximal), pler-shifted light from moving blood individuals (11 men and one woman) 15 cm (middle), and 20 cm (distal) is reflected and processed to provide aged 28 to 63 years (median, 35 below the knee joint line. In order to a flux measurement expressed in ar- years) and 11 men with PVD-DM raise skin temperature to a nonpain- bitrary perfusion units (PU) propor- aged 50 to 79 years (median, 62 ful 44°C, the probes were left in place tional to tissue blood flow. years). Healthy volunteers were re- for 15 minutes and then removed. At the West Los Angeles VA Medi- cruited for the study through flyers Within one minute of removal, a laser cal Center (WLAVAMC), the Func- posted at the WLAVAMC. Among Doppler imager (Moor Instruments, tional Perfusion Laboratory team is volunteers, individuals were excluded Devon, UK) scanned the three heated called upon to evaluate patients who if they had known peripheral vascu- sites and adjacent area. In healthy are referred from various clinical ser- lar disease, diabetes, hypercholester- participants only, LDI scanning was vices, such as the limb preservation olemia, Raynaud disease, coronary repeated at five, 10, 15, 20, 25, and and amputee clinics, for diagnosis artery disease, cerebral vascular dis- 30 minutes after removal of the heat- of microcirculation abnormalities ease, prior amputation, skin diseases, ing probes. LDI measurements were and for guidance regarding wound or acute illness; had used tobacco in not repeated in participants with care, treatment of peripheral vascu- the previous six months; or were tak- PVD-DM due to concerns about par- lar disease, and surgical planning. ing medications known to alter vessel ticipants’ discomfort. Traditionally, the laboratory team re- reactivity (nitrates).

lied upon TcPO2 to assess cutaneous The participants with PVD-DM Data analysis microperfusion after thermal stress in had been referred to the Functional Regions of interest (ROIs) were such patients. Recently, however, Perfusion Laboratory for vascular mapped onto the LDI photo images the staff wondered whether scanning studies and were considered candi- by tracing the outer edge of the heat- LDI technology, applied in a similar dates for lower extremity amputation. ing probes. When the probes were manner, could add valuable informa- Of these 11 participants, 10 under- removed, these ROIs were superim- tion to these assessments. went an amputation four to 98 days posed on the serial LDI images to As a first step in evaluating the after the LDI study (eight below the ensure accurate localization of the practicality and reproducibility of knee, one through the knee, and one thermally challenged skin areas. LDI technology in this setting, we transmetatarsal). Mean and peak flux levels were undertook a study to increase our All participants gave informed con- recorded, using the Moor LDI soft- understanding of the expected nor- sent to participate in the study, which ware, within ROIs at the heated sites

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and in equivalent, adjacent, non- sents the difference between flux at SM analysis heated areas. Group averages, differ- the border of the heating element and Images from individual heated sites ences, and ratios of peak and mean at the distance farthest away from it, indicated a significant spatial vari- flux were calculated for both heated B is the reciprocal of the space con- ability that precluded a simple direct and nonheated areas. Significance be- stant for flux decay, and C is the evaluation of flux (Figure 1). In order tween group mean differences was asymptotic value of flux away from to provide average flux values while assessed by analysis of variance, fol- the heated area. These parameters preserving the spatial information, lowed by multiple contrasts with were calculated by nonlinear regres- the data were analyzed using the SM the Fisher least significant difference sion with a Newton-Gauss algorithm. approach described earlier. With this procedure when three means were technique, we created plots of aver- contrasted (comparisons between the RESULTS age flux of all pixels within the image three sites in healthy participants) over their Euclidian distance away or by Student t tests when means of The microvascular response: from the center of the heated area. healthy and PVD-DM populations Normal versus ischemic limbs Within each group of participants, were compared. A sharp increase in blood flow was we found no statistically significant The dependence of flux on dis- observed within the skin areas cov- differences between the three calf po- tance from the center of the heated ered by the heating probes in both sitions studied. Thus, an average of area (thermal hyperemia profile) was healthy and PVD-DM groups. This the three decay slopes was used to assessed using an originally devel- response was more blunted, how- calculate a single set of equation pa- oped spatial modeling (SM) program. ever, in the PVD-DM subjects. Since rameters for each participant. These It involved measuring flux on all there was no significant difference values were used for comparison be- pixels within a 1,600-mm2 region between flux values at the three pos- tween healthy participants and the containing the heated area drawn on terior calf sites in either group, these participants with PVD-DM. Average the LDI flux image. This process values were averaged. The postheat flux was found to decay exponen- was automated by exporting the im- mean flux in healthy participants was tially with distance away from the ager data as a text file and processing more than twice that of the partici- heating element in both healthy and it with a script written in MATLAB pants with PVD-DM (Table). Even in PVD-DM participants, with a space (MathWorks, Inc.). The values of all nonheated skin areas, the mean flux constant of 2.6 mm (Figure 2). points equidistant to the center of was 34% greater in the healthy group the heated area were averaged and dis than in the PVD-DM group. Flux ra- Temporal response in healthy played as a function of distance from tios were calculated by dividing the participants the center at 1-mm intervals. The dis- mean and peak flux values for heated The time course of the blood flow re- sipation of the heat hyperemia with skin regions by values of neighboring sponse to topical heat was studied in distance was quantified by fitting nonheated skin areas. These ratios the healthy participants (Figure 3). the values of flux beyond the border also were greater in the healthy group Flux levels recorded at one and five of the heating element (FD) and than the PVD-DM group, which re- minutes after removal of the heating their distance (D) to the first order flects a more vigorous microvascular probe were similar, but values beyond –B • D rate equation: FD = A • e + C. In hyperemic response to heat among five minutes showed slow temporal this model, the parameter A repre- the healthy participants. decay. No significant differences be-

Table. Comparison of heated and nonheated flux values and flux ratios Mean flux (PUa) Ratio of heated to nonheatedb Group Heated Nonheated Mean flux Peak flux Healthy group (SE) 403.2 (49.4) 113.7 (8.6) 4.09 (0.47) 5.08 (0.47) PVD-DMc group (SE) 192.7 (25.4) 84.8 (7.8) 2.24 (0.16) 3.09 (0.26) P value < .001 .02 < .001 < .001 aPU = perfusion units. bA higher ratio reflects a more vigorous microvascular response to heat. cPVD-DM = peripheral vascular disease and diabetes mellitus.

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tween the three calf positions were found. When the averaged values were analyzed, heated and nonheated areas showed statistically significant Healthy participant

differences in peak and mean flux at ) a all time points. Average (SE) mean flux recorded 30 minutes after probe removal was still much higher in the Flux (PU heated areas than in the nonheated areas: 188 (17.8) PU versus 100 (5.9) PU, repectively (P < .001). The same was true for average (SE) peak flux, which was 694 (93.6) PU in the heated areas and 230 (17.8) PU in Distance (mm) Distance (mm) the nonheated areas (P < .001). Investigating possible confounders Since the two groups of participants PVD-DMb participant had substantially different median ages (35 years for the healthy participants versus 62 for those with PVD-DM), we investigated any pos- Flux (PU) sible dependence of flux on age using linear regression analysis. Only the PVD-DM population exhibited a significant trend of decreasing flux with age, and this phenomenon was observed only for the nonheated areas. Distance (mm) Distance (mm) Baseline skin surface temperature did not differ between the three calf positions used in healthy partici- Figure 1. Laser Doppler images of one sample heated region in a sample healthy par- pants. The pooled average (SE) of the ticipant (top) and a sample participant with PVD-DM (bottom). Scanning laser Doppler images from individual heated sites displayed spatial variability and increased flux mea- three sites was 32.7ºC (0.16ºC) for sured in PU in both healthy participants and those with PVD-DM. Images were analyzed the healthy participants and 33.1ºC using a spatial modeling technique to calculate a space constant to reflect the decay of (0.27ºC) for those with PVD-DM—a hyperemic response over distance from the center of the heating probe. aPU = perfusion nonsignificant difference. units. bPVD-DM = peripheral vascular disease and diabetes mellitus. Discussion greater disparity between the two shown that such deficits improve Considerations for the use of groups occurred in the heated condi- after successful revascularization.29 LDI in diabetic patients tion. This finding can be attributed, The unique advantages of scan- In this study, scanning LDI was able in part, to the direct effect of diabetes- ning LDI allowed us to preserve spa- to differentiate skin microperfusion associated impairment of microvas- tial information and characterize the function between groups of healthy cular perfusion reserve capacity. Such flux decay with distance from the participants and participants with decreases have been reported in dia- heated center using a simple method PVD-DM. The participants with betic patients without ischemia.9,27,28 that would be implausible with other PVD-DM had significantly lower There is also, however, a likely contri- known microvascular techniques. peak and mean flux values in both bution from macrovascular dysfunc- The distance over which the hyper- heated and nonheated test sites. The tion, as Arora and colleagues have emic response tapered was very short

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Continued from page 30 Thermal Hyperemia Profile (with a space constant of 2.6 mm) PVD-DMPVD-DMa group NORMALHealthy group in both the healthy participants and those with PVD-DM. In practical 800 terms, this means that neighboring test probes could be placed within a 700 centimeter of one another without 600 interfering significantly with true regional microperfusion variability. 500 ) This may be helpful when assessing b patients with multiple skin defects or 400 variable sites of interest in the course Flux (PU of planning amputations, wound care, FLUX (P.U.) 300 or other treatment interventions. Temporal decay of the heat- 200 induced hyperemia was very slow, Heating element with greater than 55% of the maximal 100 Heating Element ProbeProbe Border border flux increase still present 30 minutes 0 after probe removal. This finding sug- 0 5 10 15 20 gests that LDI is not feasible for mak- DistanceDistance from from Center center (mm) (mm) ing serial images over a short period of time—but would be more suitable Figure 2. Spatial decay of heat-induced flux response for healthy and PVD-DM groups for discrete flux measurements. recorded one minute after removal of heat probes. Average flux values were significantly This phenomenon also suggests greater in healthy participants than in those with PVD-DM at all points measured. aPVD- that the flux increase is independent DM = peripheral vascular disease and diabetes mellitus. bPU = perfusion units. of an axonal reflex. The response of skin blood flow to local heat is mediated by different mechanisms than ings is hampered by a lack of data. To Is age a factor? those of thermoregulatory responses date, wound healing and amputation The dependence of heat-induced hy- to enhanced core temperature.30 Noci- outcomes have been better correlated peremia on age has been studied by 36–38 ceptive C fibers appear to be involved with TcPO2 cut-off values than LDI several authors. Evans and col- in the initial phase of heat-induced results, and the 2000 report of the leagues found that hyperemia de- vasodilation, and it has been proposed Transatlantic Inter-Society Consensus creased with age in certain skin areas that an axonal reflex is responsible included diagnostic guidelines only when comparing a group of young

for the propagation of the response for TcPO2 measurements. For this individuals (mean age, 21 years) at a distance from the site of thermal reason, while our Functional Perfu- with an older group (mean age, 76 challenge.31 The sustained hyperemic sion Laboratory currently uses both years).37 Minson and colleagues

level of greater than 15 minutes we TcPO2 and scanning LDI to assess cu- found that the response in a group observed, however, suggests other taneous microvascular perfusion after of participants aged 69 to 84 years mechanisms.32,33 Locally released ni- thermal stress, we report diagnostic was about 10% lower than that of a tric oxide may play a role, as nitric impressions and predictions based on group aged 18 to 24 years.38 The lack

oxide synthase inhibitors have been TcPO2 findings. LDI data, which are of age-related effects observed in our 32 shown to attenuate late hyperemia. collected after the TcPO2 measure- study could be due to the limited age Other vasoactive mechanisms prob- ments at the same limb sites of interest, range (27 to 63 years) and the small ably are involved as well,34 since are included in the report with less em- number of study participants. antidromic vasodilation is known phasis on the predictive value. Given to decay with a half-life of one to the advantages LDI offers, however, in summary three minutes once stimulation is we hope that future research will Scanning LDI is a simple, noninva- discontinued.35 provide clinical correlations with sive tool that can be used to detect At present, the ability to base clini- specific flux values to serve as addi- abnormal microvascular function in cal recommendations upon LDI find- tional guidelines in our reports. diabetic patients with macrovascu-

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Disclaimer Nonheated mean Heated mean The opinions expressed herein are those Nonheated peak Heated peak of the authors and do not necessarily reflect those of Federal Practitioner, Quadrant HealthCom Inc., the U.S. government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug ) a combinations—including indications, contraindications, warnings, and adverse effects—before administering Flux (PU pharmacologic therapy to patients. REFERENCES 1. Miller DR, Safford MM, Pogach LM. Who has diabetes? Best estimates of diabetes prevalence in the Department of Veterans Affairs based on computer- ized patient data. Diabetes Care. 2004;27(suppl 2): B10–B21. 2. Diabetes data and trends: Hospitalization. CDC web site. http://www.cdc.gov/diabetes/statistics /hospitalization_national.htm. Accessed May 21, 2008. Time (min) 3. Reiber GE, Boyko EJ, Smith DG. Chapter 18. Lower extremity foot ulcers and amputations in Figure 3. Temporal decay of flux in healthy participants. More than 55% of the maximal diabetes. In: Diabetes in America. 2nd ed. Bethesda, MD: National Institutes of Health; 1995:409–428. heat-induced flux increase was still present at 30 minutes. Differences between heated and http://diabetes.niddk.nih.gov/dm/pubs/america/pdf nonheated areas were statistically significant at all points in time. aPU = perfusion units. /chapter18.pdf. Accessed May 21, 2008. 4. Gonzalez EG, Corcoran PJ, Reyes RL. Energy expenditure in below-knee amputees: Corre- lation with stump length. Arch Phys Med Rehab. 1974;55(3):111–119. lar disease who are at high risk for short timeframe. Further study of the 5. Harrington C, Zagari MJ, Corea J, Klitenic J. A cost amputation. The lower peak and correlation between maximal micro- analysis of diabetic lower-extremity ulcers. Diabetes Care. 2000;23(9):1333–1338. mean flux in the PVD-DM group vascular reserve capacity (in terms 6. Pecoraro RE, Reiber GE, Burgess EM. Pathways was evident in both the thermally of flux ratios) and clinical outcomes to diabetic limb amputation. Basis for prevention. Diabetes Care. 1990;13(5):513–521. stressed and baseline skin regions in of diabetes-related lower extremity 7. Humphrey LL, Palumbo PJ, Butters MA, et al. The comparison to healthy control par- amputations may help establish bet- contribution of non–insulin-dependent diabetes to lower-extremity amputation in the community. ticipants. We found mean flux values ter guidelines for treatment interven- Arch Intern Med. 1994;154(8):885–892. and heated/nonheated flux ratios to tion and prediction of wound healing 8. Williams DT, Harding KG, Price P. An evaluation of ● the efficacy of methods used in screening for lower- be meaningful parameters for distin- for specific amputation levels. limb arterial disease in diabetes. Diabetes Care. guishing normal from ischemic lower 2005;28(9):2206–2210. 9. Mayrovitz HN, Larsen PB. Functional microcircula- limb microperfusion. The sharp spa- Acknowledgements tory impairment: A possible source of reduced skin tial decay of heat-induced hyper- This work was supported, in part, by oxygen tension in human diabetes mellitus. Micro- vasc Res. 1996;52(2):115–126. emia justifies close placement of test the VA Rehabilitation Research and 10. Lassen NA, Holstein P. Use of radioisotopes in as- probes without risk of interference Development Merit Review Program sessment of distal blood flow and distal blood pressure in arterial insufficiency. Surg Clin North Am. when attempting to quantify regional (A2860R) and a Senior Research Ca- 1974;54(1):39–55. skin perfusion deficits. Temporal dis- reer Scientist Award (B2541SA) to Dr. 11. Ohta T. Noninvasive technique using thallium-201 for predicting ischaemic ulcer healing of the foot. sipation of the normal hyperemic O. Scremin. Br J Surg. 1985;72(11):892–895. response is too slow to be explained 12. Beard JD, Scott DJ, Evans JM, Skidmore R, Hor- rocks M. Pulse-generated runoff: A new method solely by an axonal reflex and makes Author disclosures of determining calf vessel patency. Br J Surg. the technique better suited for distinct The authors report no actual or poten- 1988;75(4):361–363. 13. Gschwandtner ME, Ambrózy E, Schneider B, Fas- “snapshot” flux assessments, rather tial conflicts of interest with regard to ching S, Willfort A, Ehringer H. Laser Doppler im- than serial measurements within a this article. aging and capillary microscopy in ischemic ulcers.

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quality. This collaboration illustrates and adverse effects—before administering Palliative Care. Pittsburgh, PA: National Con sensus Project; May 2004. http://www.national the potential for GRECCs to improve pharmacologic therapy to patients. consensusproject.org/Guidelines_Download.asp. clinical care, education, and research Accessed May 20, 2008. 7. National Quality Forum. A National Framework in their facilities and across entire References and Preferred Practices for Palliative and Hospice networks. ● 1. About AAHPM. American Academy of Hospice Care Quality. Washington, DC: National Quality and Palliative Medicine web site. http://www. Forum; 2006. aahpm.org/about/index.html. Accessed May 20, 8. Chang VT, Hwang SS, Kasimis B, Thaler HT. Author disclosures 2008. Shorter symptom assessment instruments: The 2. American Geriatrics Society Ethics Committee. Condensed Memorial Symptom Assessment Scale The authors report no actual or potential American Geriatrics Society (AGS) Position (CMSAS). Cancer Invest. 2004;22(4):526–536. conflicts of interest with regard to this Statement: The Care of Dying Patients. http://www. 9. Karnofsky DA, Burchenal JH. The clinical evalu- americangeriatrics.org/products/positionpapers ation of chemotherapeutic agents in cancer. In: column. /careofd.shtml. Updated May 2007. Accessed MacLeod CM, ed. Evaluation of Chemotherapeutic May 21, 2008. Agents. New York: Columbia University Press; 3. About CAPC. Center to Advance Palliative 1949:196. Disclaimer Care web site. http://www.capc.org/about-capc. 10. Penrod JD, Cortez T, Luhrs CA. Use of a report The opinions expressed herein are those of Accessed May 20, 2008. card to implement a network-based palliative 4. VA Nationwide Palliative Care Network, 2006. care program. J Palliat Med. 2007;10(4):858– the authors and do not necessarily reflect http://www.hospice.va.gov/. Accessed January 4, 860. those of Federal Practitioner, Quadrant 2006. 11. Veterans satisfaction. VA Office of Quality and 5. Department of Veterans Affairs. Palliative Performance intranet site. http://vaww.oqp/oqp_ HealthCom Inc., the U.S. government, or Care Consult Teams (PCCT). Washington, DC: services/veterans_satisfaction/vss.asp. Accessed any of its agencies. Please review com- Department of Veterans Affairs; February 4, May 27, 2008. 2003. VHA directive 2003-008. http://www. 12. Penrod JD, Deb P, Luhrs C, et al. Cost and uti- plete prescribing information for specific ethosconsult.com/files/12003008.pdf. Accessed lization outcomes of patients receiving hospital- drugs or drug combinations—including May 20, 2008. based palliative care consultation. J Palliat Med. 6. National Consensus Project for Quality Palliative 2006;9(4):855–860. indications, contraindications, warnings, Care. Clinical Practice Guidelines for Quality

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Atherosclerosis. 1999;142(1):225–232. 22. Fairs SL, Ham RO, Conway BA, Roberts VC. Limb cholinergic nerve cotransmission. Circ Res. 14. Ubbink DT, Jacobs MJ, Tangelder GJ, Slaaf DW, perfusion in the lower limb amputee—A com- 1995;77(6):1222–1228. Reneman RS. The usefulness of capillary micros- parative study using a laser Doppler flowmeter 31. Magerl W, Treede RD. Heat-evoked vasodilatation copy, transcutaneous oximetry and laser Doppler and a transcutaneous oxygen electrode. Prosthet in human hairy skin: Axon reflexes due to low- fluxmetry in the assessment of the severity of Orthot Int. 1987;11(2):80–84. level activity of nociceptive afferents. J Physiol. lower limb ischaemia. Int J Microcirc Clin Exp. 23. Lantsberg L, Goldman M. Laser Doppler flow- 1996;497(pt 3):837–848. 1994;14(1-2):34–44 metry, transcutaneous oxygen tension mea- 32. Minson CT, Berry LT, Joyner MJ. Nitric oxide 15. Management of peripheral arterial disease (PAD). surements and Doppler pressure compared in and neurally mediated regulation of skin TransAtlantic Inter-Society Consensus (TASC). patients undergoing amputation. Eur J Vasc Surg. blood flow during local heating. J Appl Physiol. Section D: Chronic critical limb ischaemia. Eur 1991;5(2):195–197. 2001;91(4):1619–1626. J Vasc Endovasc Surg. 2000;19(suppl A):S144– 24. Essex TJ, Byrne PO. A laser Doppler scanner 33. Golay S, Haeberli C, Delachaux A, et al. Local S243. for imaging blood flow in skin. J Biomed Eng. heating of human skin causes hyperemia without 16. Krishnan ST, Baker NR, Carrington AL, Rayman 1991;13(3):189–194. mediation by muscarinic cholinergic receptors G. Comparative roles of microvascular and nerve 25. Stücker M, Heese A, Hoffmann K, Röchling A, or prostanoids. J Appl Physiol. 2004;97(5):1781– function in foot ulceration in type 2 diabetes. Altmeyer P. Precision of laser Doppler scanning in 1786. Diabetes Care. 2004;27(12):1343–1348. clinical use. Clin Exp Dermatol. 1995;20(5):371– 34. Vinik AI, Erbas T, Park TS, Stansberry KB, 17. Heller L, Levin LS, Klitzman B. Laser Doppler 376. Scanelli JA, Pittenger GL. Dermal neurovascular flowmeter monitoring of free-tissue transfers: 26. Kubli S, Waeber B, Dalle-Ave A, Feihl F. dysfunction in type 2 diabetes. Diabetes Care. Blood flow in normal and complicated cases. Reproducibility of laser Doppler imaging of skin 2001;24(8):1468–1475. Plast Reconstr Surg. 2001;107(7):1739–1745. blood flow as a tool to assess endothelial func- 35. Häbler HJ, Wasner G, Jänig W. Interaction 18. Gebuhr P, Jørgensen JP, Vollmer-Larsen B, Nielsen tion. J Cardiovasc Pharmacol. 2000;36(5):640– of sympathetic vasoconstriction and antidromic SL, Alsbjørn B. Estimation of amputation level 648. vasodilatation in the control of skin blood flow. with a laser Doppler flowmeter. J Bone Joint Surg 27. Khan F, Elhadd TA, Greene SA, Belch JJ. Impaired Exp Brain Res. 1997;113(3):402–410. Br. 1989;71(3):514–517. skin microvascular function in children, adoles- 36. Algotsson A, Nordberg A, Winblad B. Influence of 19. Barachini P, Vezzoni GM, Palombo C, Franzoni cents, and young adults with type 1 diabetes. age and gender on skin vessel reactivity to endo- F, Bigalli G. Skin blood flow pattern in burns Diabetes Care. 2000;23(2):215–220. thelium-dependent and endothelium-indepen- outcomes. Burns. 2004;30(4):312–316. 28. Jaap AJ, Shore AC, Tooke JE. Relationship dent vasodilators tested with iontophoresis and a 20. Choi CM, Bennett RG. Laser Dopplers to deter- of insulin resistance to microvascular dysfunc- laser Doppler perfusion imager. J Gerontol Series mine cutaneous blood flow. Dermatol Surg. tion in subjects with fasting hyperglycaemia. A Biol Sci Med Sci. 1995;50(2):M121–M127. 2003;29(3):272–280. Diabetologia. 1997;40(2):238–243. 37. Evans E, Rendell M, Bartek J, et al. Thermally- 21. Karanfilian RG, Lynch TG, Zirul VT, Padberg 29. Arora S, Pomposelli F, LoGerfo FW, Veves A. induced cutaneous vasodilatation in aging. J FT, Jamil Z, Hobson RW II. The value of laser Cutaneous microcirculation in the neuropathic Gerontol. 1993;48(2):M53–M57. Doppler velocimetry and transcutaneous oxygen diabetic foot improves significantly but not com- 38. Minson CT, Holowatz LA, Wong BJ, Kenney tension determination in predicting healing of pletely after successful lower extremity revascu- WL, Wilkins BW. Decreased nitric oxide- ischemic forefoot ulcerations and amputations larization. J Vasc Surg. 2002;35(3):501–505. and axon reflex-mediated cutaneous vasodilation in diabetic and nondiabetic patients. J Vasc Surg. 30. Kellogg DL, Pérgola PE, Piest KL, et al. Cutaneous with age during local heating. J Appl Physiol. 2002; 1986;4(5):511–516. active vasodilation in humans is mediated by 93(5):1644–1649.

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