Diabetes - Laser Doppler Monitoring And Imaging Diabetic foot/ulcers/non-healing wounds We recommend: the moorLDI2 or the moorLDLS2 Diabetic foot ulcers are a chronic, severe and common complication in diabetic Introduction patients’ often resulting in limb amputation and increasing the death rate. The combination of poor nutritional blood flow, endothelial dysfunction and neuropathy Diabetes mellitus is a chronic condition in which a person has hyperglycaemia as a result of the pancreas not producing etc. all render the diabetic foot vulnerable to the formation of non-healing ulcers. sufficient quantities of insulin, or an inappropriate response of the cells of the body to the insulin which is produced. In either Studies aiming to correct cellular defects/abnormalities often require the monitoring of case poor control of diabetes leads to a wide range of long term complications, some of which involve the blood vessels, microvascular blood flow, and in some cases indicate that increased perfusion at the leading to problems such as non-healing wounds (ulcers), endothelial dysfunction, peripheral vascular disease, and in severe base of diabetic foot ulcers is linked to increased healing (Newton et al, 2002), and cases leads to limb amputation when neuropathy of the feet is combined with reduced blood flow. According to the World that control of inflammation can aid diabetic ulcer healing rate (Lau et al, 2009). The Health Organization (2010), at least 220 million people worldwide suffer from diabetes, with this number projected to double laser Doppler imaging system, moorLDI2-IR, enables the user to image changes in between 2005 and 2030. blood flow over the entire wound surface, providing the user with a full colour 2-dimentional map of microvascular flow. Laser Doppler studies of microvascular blood flow in diabetic patients – monitoring or imaging? ULCERS/NON-HEALING WOUNDS - ask us about laser Doppler imaging with the moorLDI2-IR or the moorLDLS2. Moor Instruments designs and manufactures laser Doppler systems and accessories to investigate blood flow in the We recommend: the moorVMS-LDF and moorVMS-PRES Post-occlusive reactive hyperaemia (PORH) microcirculation. The laser Doppler technique is well established as the most convenient means of assessing tissue blood flow non-invasively and continuously. Both Monitoring and Imaging systems are available, each of which is particularly suited The increase in microvascular blood flow following arterial occlusion, post occlusion to a range of studies and applications. Monitoring allows continuous assessment of flow at one or more sites with the use reactive hyperaemia (PORH), can be assessed using the non-invasive laser of optic probes in contact with the tissue. Laser Doppler imaging is a non contact technique and a laser beam is used Doppler technique. Following release of the arterial occlusion there is a marked rather than transmitting light with optic probes. Accessories are also available to investigate the effect of thermal, drug and transient increase in microvascular blood flow to the ischaemic tissues, referred to pressure stimulation on the microcirculation as post-occlusive reactive hyperaemia (PORH). Analysis of the PORH response in diabetes patients has been reported to provide an indication of the presence of Peripheral vascular disease (PVD), including peripheral arterial occlusive disease (PAOD) and peripheral artery disease (PAD), microangiopathy (Strain et al, 2005. Yamamoto-Suganuma & Aso, 2009). PORH is a common complication in Diabetes patients ultimately resulting in impaired skin microcirculation for example of the leg measurements can be simply and reproducibly performed using the moorVMS-LDF monitor combined with the automated pressure cuff controller, the moorVMS-PRES, and foot. The use of laser Doppler for the study of microvascular blood flow in diabetic patients is used in a wide range of teamed with the powerful PC software for analysis of the PORH response curve. studies of PVD – for which different laser Doppler techniques are recommended. In the following sections a brief overview of commonly studied conditions are described and the appropriate laser Doppler technology indicated. PORH - ask us about automatic pressure cuff control with the moorVMS-PRES and laser Doppler monitoring with the moorVMS-LDF. For further details of any these applications and the laser Doppler technology used, please contact your Moor Instruments representative who will be happy to help and advise you regarding your specific application. Endothelial Function/Dysfunction We recommend: moorVMS-LDF and Iontophoresis with the MIC2 Endothelial dysfunction is a pathological state of the lining of the blood vessels (the endothelium) and is known to contribute to, or result from, several disease states including diabetes. Laser Doppler methods which have been described in the literature for the monitoring of endothelial function/dysfunction vary depending upon the experimental set-up. Cohen et al, 2008, investigated the effect of a long-term exercise program on endothelial function (EF). EF was measured using laser Doppler monitoring of blood flow in response to vasoactive compounds. The group used Iontophoresis to deliver the vasoactive drugs acetylcholine (Ach) and Sodium Nitroprusside (NaNP) into the skin. 1 2 Diabetes - Laser Doppler Monitoring And Imaging Diabetic foot/ulcers/non-healing wounds We recommend: the moorLDI2 or the moorLDLS2 Diabetic foot ulcers are a chronic, severe and common complication in diabetic Introduction patients’ often resulting in limb amputation and increasing the death rate. The combination of poor nutritional blood flow, endothelial dysfunction and neuropathy Diabetes mellitus is a chronic condition in which a person has hyperglycaemia as a result of the pancreas not producing etc. all render the diabetic foot vulnerable to the formation of non-healing ulcers. sufficient quantities of insulin, or an inappropriate response of the cells of the body to the insulin which is produced. In either Studies aiming to correct cellular defects/abnormalities often require the monitoring of case poor control of diabetes leads to a wide range of long term complications, some of which involve the blood vessels, microvascular blood flow, and in some cases indicate that increased perfusion at the leading to problems such as non-healing wounds (ulcers), endothelial dysfunction, peripheral vascular disease, and in severe base of diabetic foot ulcers is linked to increased healing (Newton et al, 2002), and cases leads to limb amputation when neuropathy of the feet is combined with reduced blood flow. According to the World that control of inflammation can aid diabetic ulcer healing rate (Lau et al, 2009). The Health Organization (2010), at least 220 million people worldwide suffer from diabetes, with this number projected to double laser Doppler imaging system, moorLDI2-IR, enables the user to image changes in between 2005 and 2030. blood flow over the entire wound surface, providing the user with a full colour 2-dimentional map of microvascular flow. Laser Doppler studies of microvascular blood flow in diabetic patients – monitoring or imaging? ULCERS/NON-HEALING WOUNDS - ask us about laser Doppler imaging with the moorLDI2-IR or the moorLDLS2. Moor Instruments designs and manufactures laser Doppler systems and accessories to investigate blood flow in the We recommend: the moorVMS-LDF and moorVMS-PRES Post-occlusive reactive hyperaemia (PORH) microcirculation. The laser Doppler technique is well established as the most convenient means of assessing tissue blood flow non-invasively and continuously. Both Monitoring and Imaging systems are available, each of which is particularly suited The increase in microvascular blood flow following arterial occlusion, post occlusion to a range of studies and applications. Monitoring allows continuous assessment of flow at one or more sites with the use reactive hyperaemia (PORH), can be assessed using the non-invasive laser of optic probes in contact with the tissue. Laser Doppler imaging is a non contact technique and a laser beam is used Doppler technique. Following release of the arterial occlusion there is a marked rather than transmitting light with optic probes. Accessories are also available to investigate the effect of thermal, drug and transient increase in microvascular blood flow to the ischaemic tissues, referred to pressure stimulation on the microcirculation as post-occlusive reactive hyperaemia (PORH). Analysis of the PORH response in diabetes patients has been reported to provide an indication of the presence of Peripheral vascular disease (PVD), including peripheral arterial occlusive disease (PAOD) and peripheral artery disease (PAD), microangiopathy (Strain et al, 2005. Yamamoto-Suganuma & Aso, 2009). PORH is a common complication in Diabetes patients ultimately resulting in impaired skin microcirculation for example of the leg measurements can be simply and reproducibly performed using the moorVMS-LDF monitor combined with the automated pressure cuff controller, the moorVMS-PRES, and foot. The use of laser Doppler for the study of microvascular blood flow in diabetic patients is used in a wide range of teamed with the powerful PC software for analysis of the PORH response curve. studies of PVD – for which different laser Doppler techniques are recommended. In the following sections a brief overview of commonly studied conditions are described and the appropriate laser Doppler technology indicated. PORH - ask us about automatic pressure cuff control with the moorVMS-PRES and laser Doppler monitoring with the moorVMS-LDF. For further details of any these applications and the laser Doppler technology used, please contact your Moor Instruments representative who will be happy to help and advise you regarding your specific application. Endothelial Function/Dysfunction We recommend: moorVMS-LDF and Iontophoresis with the MIC2 Endothelial dysfunction is a pathological state of the lining of the blood vessels (the endothelium) and is known to contribute to, or result from, several disease states including diabetes. Laser Doppler methods which have been described in the literature for the monitoring of endothelial function/dysfunction vary depending upon the experimental set-up. Cohen et al, 2008, investigated the effect of a long-term exercise program on endothelial function (EF). EF was measured using laser Doppler monitoring of blood flow in response to vasoactive compounds. The group used Iontophoresis to deliver the vasoactive drugs acetylcholine (Ach) and Sodium Nitroprusside (NaNP) into the skin. 1 2 Hind limb ischaemia/Angiogenesis Forst et al, 2005, investigated the impact of insulin on EF and microvascular flow in the postprandial state. Blood flow was monitored in the dorsum of the foot using a laser Doppler monitor, with vasoactive challenge performed via the Iontophoresis of Ach. We recommend: the moorLDI2-HR ENDOTHELIAL FUNCTION - ask us about laser Doppler monitoring with the moorVMS-LDF and Iontophoresis with the The formation of new blood vessels, angiogenesis, is a normal physiological MIC2. response to tissue ischaemia. The literature suggests that Diabetes patients have endothelial dysfunction and also impaired angiogenesis in response to ischaemia Skin perfusion pressure (SPP) (Huang et al, 2008). The moorLDI2-HR, high resolution laser Doppler imaging system, enables non-invasive assessment of global perfusion in the ischaemic We recommend: the moorVMS-LDF and moorVMS-PRES hind limb of mice and rats without the need for tracer dyes. Measurements can be performed over a number of days resulting in a sequence of full colour 2-dimentional Skin Perfusion Pressure (SPP) is the pressure required for restoring microcirculatory maps of microvascular flow of re-perfusion of the ischaemic limb following blood flow following release of carefully controlled occlusion. The measurement development of collateral vessels. of SPP with laser Doppler is a non-invasive test. It has proved useful in the assessment of peripheral arterial disease (PAD) for both critical ischaemia HIND LIMB ISCHAEMIA and ANGIOGENESIS - ask us about laser Doppler imaging with the moorLDI2-HR. (Castronuovo, 1997, Castronuovo et al, 1997), and also for the determination of Diabetic Peripheral Neuropathy optimal levels for amputation (Tsuji et al, 2008). There are also indications in the literature that SPP measurements are useful indicators for wound healing potential (Yamada et al, 2008). The combined moorVMS-PRES and moorVMS-LDF systems We recommend: the moorVMS-LDF and MIC2 enable simple, rapid and reproducible measurement of SPP. The user friendly PC software enables protocols to be written which exactly match user requirements for individual experimental conditions – the Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes, which user is in no way limited to pre-defined protocols. can ultimately lead to gangrene and amputation of the foot/lower limb. Symptoms of DPN in the foot/lower limb include; numbness and tingling, loss of sensation and LIMB/TOE/ANKLE & FOOT PRESSURE - ask us about automatic pressure cuff control with the moorVMS-PRES and muscle weakness. The exact mechanisms of DPN are not completely understood laser Doppler monitoring with the moorVMS-LDF. however considerable evidence indicates that abnormalities in the microvasculature contribute to nerve hypoxia (Malik et al, 2006). Toe pressure DIABETIC PERIPHERAL NEUROPATHY - ask us about laser Doppler monitoring We recommend: the moorVMS-LDF and moorVMS-PRES with the moorVMS-LDF and Iontophoresis with the MIC2. Toe Blood Pressure (TBP) is the measurement of distal limb systolic blood pressure moorVMS-LDF Probes moorVMS-PRES MIC2 moorLDI2 moorLDI2-HR moorLDLS2 Foot pressure measurements: toe, pressure, ABPI, PORH, SPP Y Y Y - - - - at the toe. TBP is particularly useful in patients with noncompressible tibial arteries, for example those suffering long-standing diabetes, renal failure or other disorders where vascular calcification is present (Clement, TASC II, 2008). TBP can be used in patients with peripheral artery disease (PAD) to assess the severity of ischaemia (Ubbink, 2004) and ultimately lead to early treatment and/or prevention of the formation of ischaemic ulcers in the lower limb. Routine measurements of TBP can be performed simply and rapidly using the moorVMS-LDF and moorVMS-PRES Peripheral Vascular Disease Y Y Y - - - - Endothelial Function/Dysfunction Y Y - Y - - - Diabetic foot ulcers/non-healing wounds - - - - Y - Y - - - - - Y - Y Y - Y - - - Hind limb ischaemia/ Angiogenesis systems with the default protocol. The user-friendly software enables user defined protocols as required for research – the user is not limited to pre-defined protocols. Diabetic Peripheral Neuropathy LIMB/TOE/ANKLE & FOOT PRESSURE - ask us about automatic pressure cuff control with the moorVMS-PRES and Table showing equipment required for a range of diabetic studies. laser Doppler monitoring with the moorVMS-LDF. References Castronuovo J. J. 1997 Diagnosis of critical limb ischemia with skin perfusion pressure measurements. The Journal of Vascular Technology, 21(3), 175-179. 3 4 Hind limb ischaemia/Angiogenesis Forst et al, 2005, investigated the impact of insulin on EF and microvascular flow in the postprandial state. Blood flow was monitored in the dorsum of the foot using a laser Doppler monitor, with vasoactive challenge performed via the Iontophoresis of Ach. We recommend: the moorLDI2-HR ENDOTHELIAL FUNCTION - ask us about laser Doppler monitoring with the moorVMS-LDF and Iontophoresis with the The formation of new blood vessels, angiogenesis, is a normal physiological MIC2. response to tissue ischaemia. The literature suggests that Diabetes patients have endothelial dysfunction and also impaired angiogenesis in response to ischaemia Skin perfusion pressure (SPP) (Huang et al, 2008). The moorLDI2-HR, high resolution laser Doppler imaging system, enables non-invasive assessment of global perfusion in the ischaemic We recommend: the moorVMS-LDF and moorVMS-PRES hind limb of mice and rats without the need for tracer dyes. Measurements can be performed over a number of days resulting in a sequence of full colour 2-dimentional Skin Perfusion Pressure (SPP) is the pressure required for restoring microcirculatory maps of microvascular flow of re-perfusion of the ischaemic limb following blood flow following release of carefully controlled occlusion. The measurement development of collateral vessels. of SPP with laser Doppler is a non-invasive test. It has proved useful in the assessment of peripheral arterial disease (PAD) for both critical ischaemia HIND LIMB ISCHAEMIA and ANGIOGENESIS - ask us about laser Doppler imaging with the moorLDI2-HR. (Castronuovo, 1997, Castronuovo et al, 1997), and also for the determination of Diabetic Peripheral Neuropathy optimal levels for amputation (Tsuji et al, 2008). There are also indications in the literature that SPP measurements are useful indicators for wound healing potential (Yamada et al, 2008). The combined moorVMS-PRES and moorVMS-LDF systems We recommend: the moorVMS-LDF and MIC2 enable simple, rapid and reproducible measurement of SPP. The user friendly PC software enables protocols to be written which exactly match user requirements for individual experimental conditions – the Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes, which user is in no way limited to pre-defined protocols. can ultimately lead to gangrene and amputation of the foot/lower limb. Symptoms of DPN in the foot/lower limb include; numbness and tingling, loss of sensation and LIMB/TOE/ANKLE & FOOT PRESSURE - ask us about automatic pressure cuff control with the moorVMS-PRES and muscle weakness. The exact mechanisms of DPN are not completely understood laser Doppler monitoring with the moorVMS-LDF. however considerable evidence indicates that abnormalities in the microvasculature contribute to nerve hypoxia (Malik et al, 2006). Toe pressure DIABETIC PERIPHERAL NEUROPATHY - ask us about laser Doppler monitoring We recommend: the moorVMS-LDF and moorVMS-PRES with the moorVMS-LDF and Iontophoresis with the MIC2. Toe Blood Pressure (TBP) is the measurement of distal limb systolic blood pressure moorVMS-LDF Probes moorVMS-PRES MIC2 moorLDI2 moorLDI2-HR moorLDLS2 Foot pressure measurements: toe, pressure, ABPI, PORH, SPP Y Y Y - - - - at the toe. TBP is particularly useful in patients with noncompressible tibial arteries, for example those suffering long-standing diabetes, renal failure or other disorders where vascular calcification is present (Clement, TASC II, 2008). TBP can be used in patients with peripheral artery disease (PAD) to assess the severity of ischaemia (Ubbink, 2004) and ultimately lead to early treatment and/or prevention of the formation of ischaemic ulcers in the lower limb. Routine measurements of TBP can be performed simply and rapidly using the moorVMS-LDF and moorVMS-PRES Peripheral Vascular Disease Y Y Y - - - - Endothelial Function/Dysfunction Y Y - Y - - - Diabetic foot ulcers/non-healing wounds - - - - Y - Y - - - - - Y - Y Y - Y - - - Hind limb ischaemia/ Angiogenesis systems with the default protocol. The user-friendly software enables user defined protocols as required for research – the user is not limited to pre-defined protocols. Diabetic Peripheral Neuropathy LIMB/TOE/ANKLE & FOOT PRESSURE - ask us about automatic pressure cuff control with the moorVMS-PRES and Table showing equipment required for a range of diabetic studies. laser Doppler monitoring with the moorVMS-LDF. References Castronuovo J. J. 1997 Diagnosis of critical limb ischemia with skin perfusion pressure measurements. The Journal of Vascular Technology, 21(3), 175-179. 3 4 Castronuovo J. J., Adera, H. M., Smiell J. M., Price, R. 1997 Skin perfusion pressure measurement is valuable in the diagnosis of critical limb ischemia. Journal of Vascular Surgery, 26 (4), 629-637. Clement D. 2008 Diagnosis and evaluation of peripheral artery disease – non invasive vascular laboratory and imaging techniques. Based on the Inter-Society Consensus. www.tasc-2-pad.org Cohen, N.D., Dunstan D. W., Robinson C., Vulikh E., Zimmet P. Z. and Shaw J. E. 2008 Improved endothelial function following 14-month resistance exercise training program in adults with type 2 diabetes. Diabetes Research and Clinical Practice, 79, 405-411 Forst T., Forst S., Strunk K., Löbig M., Welter K., Kazda C., Pfützner A. 2005 Impact of insulin on microvascular blood flow and endothelial cell function in the postprandial state in patients with Type I diabetes. Journal of Diabetes and its Complications, 19, 128-132 Huang P., Sata M., Nishimatsu H., Sumi M., Hirata Y., Nagai R. 2008 Pioglitazone ameliorates endothelial dysfunction and restores ischaemia-induced angiogenesis in diabetic mice. Biomedicine and Pharmacotherapy, 62, 46-52 Jaffer U., Aslam M., Standfield N. 2008 Impaired hyperaemic and rhythmic vasomotor response in Type 1 diabetes mellitus patients: A predictor of early peripheral vascular disease. European Journal of Endovascular Surgery, 35, 603-606 Lau T. W., Lam F. F. Y., Lau K. M., Chan Y. W., Lee K. M., Sahota D. S., Ho Y. Y., Fung K. P., Leung P. C., Lau C. B. S. 2009 Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer. Journal of Ethnopharmacology, 123, 155-162 Malik R., Veves A., Tesfaye S. 2006 Ameliorating human neuropathy: Lessons from implanting hematopoietic mononuclear cells. Experimental Neurology, 201, 7-14 Newton D. J., Khan F., Belch J. J. F., Mitchell M. R., Leese G. P. 2002 Blood flow changes in diabetic foot ulcers treated with dermal replacement therapy. The Journal of Foot & Ankle Surgery, 41(4), 233-237 Strain D.W., Chaturvedi N., Bulpitt C. J., Rajkumar C., Shore A. C. 2005 Albumin excretion rate and cardiovascular risk. Could the association be explained by early microvascular dysfunction? Diabetes, 54, 1816-1822 Tsuji, Y., Hiroto, T., Kitano, I., Tahara, S., Sugiyama, D. 2008 Importance of skin perfusion pressure in treatment of critical limb ischemia. Wound Research, Apr, Issue 4. Ubbink, D, Th. 2004 Toe blood pressure measurements in patients suspected of leg ischaemia: A new laser Doppler device compared with photoplethysmography. European Journal of Endovascular Surgery, 27, 629-634 Yamada, T., Ohta, T., Ishibashi, H., Sugimoto, I., Iwata, H., Takahashi, M., Kawanishs, J. (2008) Clinical reliability and utility of skin perfusion pressure measurement in ischemic limbs – Comparison with other non-invasive diagnostic methods. Journal of Vascular Surgery, 47(2), 318-323. Yamamoto-Suganuma R., Aso Y. 2009 Relationship between post-occlusive forearm skin reactive hyperaemia and vascular disease in patients with Type 2 diabetes – A novel index for detecting micro- and macrovascular dysfunction using laser Doppler flowmetry. Diabet Med 26, 83-88. Moor Instruments Ltd Millwey Axminster Devon EX13 5HU UK tel +44 (0)1297 35715 fax +44 (0)1297 35716 email [email protected] website www.moor.co.uk Moor Instruments Inc 501 Silverside Road Suite # 66 Wilmington DE 19809 USA tel (302) 798 7470 fax (302) 798 7299 email [email protected] Issue 1 5
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