Clin Physiol Funct Imaging. 2013 Jul;33(4):302-6.

Heat-washout – an objective method for diagnosing neuropathy and atherosclerosis in diabetic patients.

Midttun M, Snorgaard O.

Departments of Geriatrics, and Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.



Background: The heat-washout method is an objective method that measures cutaneous blood flow rate (BFR) in ml/100g/min, previously found useful for measuring toe BFR in non-diabetic patients with claudication.

Aim: The method is used for evaluating the presence of a veno-arteriolar reflex (VAR) in the forefoot and signs of atherosclerosis in the first toe in type 2 diabetics.

Methods: Nine type 2 diabetics for +10 years and peripheral neuropathy, median age 62, and 9 healthy subjects without diabetes, median age 52 were examined for the presence of a VAR in the forefoot.  A VAR was present when BFR decreased 25 % or more with the foot 50 cm below heart level. Examinations for atherosclerosis were made in the pulp of the first toe. An increase in BFR of 50% or more with the foot 50 cm below heart level indicated the presence of atherosclerosis.

Results: The VAR was significantly attenuated in type 2 diabetics with neuropathy compared to controls, (p<0.01). Only one patient with known neuropathy and diabetes showed a reflex compared to 8 out of 9 controls (p<0.01). The VAR was correlated to the vibration perception threshold measured with biothesiometry (r = – 0.661, p = 0.0003). Two patients with type 2 diabetes and neuropathy without clinical sign of peripheral artery disease had an abnormal response similar to that seen in subjects with intermittent claudication.

Conclusion: The heat-washout method seems useful as an objective method for evaluating as well the presence of a VAR as atherosclerosis in type 2 diabetics.

© 2013 The Authors Clinical Physiology and Functional Imaging © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

PMID: 23692620



The heat-washout method is a non-invasive method used for measuring blood flow rate (BFR) in the skin in a depth of 2 – 3 mm in ml (g·min)¯¹. The measurements are made with a probe with a diameter of about 2.3 cm containing a central heating element with a diameter of about 1 cm. The probe can heat and measure local temperature simultaneously, and is constructed with a thermostatically controlled cap that ensures that no heat escapes to the surroundings, but only to the skin where the probe is mounted. The probe is fixed with adhesive tape on the skin area you want to examine. Then the probe is adjusted to heat to a few degrees above normal skin temperature, typically 40 degrees C. The devise works on electricity from the mains.

After heating for at few minutes to ex 40 degrees a stable heat gradient between the probe and the skin has been obtained, and washout of the surplus of heat can now be started by turning off the heat supply manually by removing the heating element 1 mm from the skin by a small screw on the top of the probe. The local temperature under the probe is registered automatically every five seconds, and washout is stopped manually when the local temperature has fallen to normal skin temperature when the washout curve is horizontal. Then the basis temperature (the temperature obtained when the curve is horizontal) is subtracted from the registered temperatures, the results are plotted in a semilogarithmic diagram, and subsequently BFR can be calculated according to the formula of Kety f = k·λ·100ml (100g·min)¯¹. The formula was previously used for calculating BFR measured by 133Xenon in muscles tissue, and later cutaneous tissue, and now it is used for heat-washout as the principles are identical.  λ is the coefficient of distribution between cutaneous tissue and blood at equilibrium = 0.954 ml ·g ¯¹, and for simplicity 1 ml ·g ¯¹ is used.

Heat-washout and 133-xenon-washout are the two only methods that measure absolute BFR in ml (g·min)¯¹ in quantitative values. It takes from 1½ minute to 10 – 15 minutes to make a washout curve dependent on the flow rate – the fastest washout is from the thumb pulp, the slowest from a an atherosclerotic toe. With the heat-washout method it is possible to measure BFR in all skin areas, and heat-washout partly substitutes the 133-Xenon washout. A small disadvantage by using the heat-washout method is that BFR under the probe is increases slightly with the increasing probe temperature as the arterioles supplying the capillaries are temperature dependent, and consequently BFR is not measured at neutral/undisturbed skin temperature.

Other methods used for measuring skin blood flow such as laser Doppler measure the linear flow rate of red blood cells in an undefined depth in the measuring area, and furthermore the result is dependent on the amount of red blood cells. That is why laser Doppler can only be used at heart level and does not measure an absolute blood flow rate in ml (g·min)¯¹. Ankle- and toe blood pressure measure blood pressure locally and not BFR, and no of these methods are optimal when examining patients with atheromathosis/athesclerosis These vessels are stiff vessels and therefore the measured values are overestimated.

The advantages of using the heat-washout method are that it seems a better diagnostic tool, it has no side effects, causes no pain, no complications, and no risks. The only real alternative is radioactive 133-Xenon that is not available anymore. So far the heat-washout method has among others been used for diagnosing peripheral atherosclerosis, measuring the presence or absence of a veno-arteriolar reflex in patients with diabetes, and at the moment it is being used for measuring BFR in patients with and without diabetes with foot ulcers. The perspectives seem wide and the heat-washout method seems especially useful in diagnosing and controlling patients with peripheral atheromatosis/atherosclerosis with and without diabetes.



Figure 1. A (left): Device for measuring heat-washout. Probe mounted in the 1st toe; C (right): One single measurement of heat-washout.


DM-fig2Figure 2. The relationship between vibration perception threshold (V) and the size of the veno-arteriolar reflex (%) in 9 diabetic patients (•) and 9 healthy control subjects (m).  Pearson’s test for linear correlation: r= -0.661, p=0.003 for all subjects and r= -0.492, p=0.178 for diabetic subjects only.


DM-Fig.2AFigure 2A.  Measuring blood flow rate in the forefoot to examine whether a veno-arteriolar reflex is present or not.

DM-fig3Figure 3. Blood flow rate response in the pulp of the 1st toe to lowering of the foot 50 cm below heart level in 9 type diabetic patients (DM), 7 patients with intermittent claudication (IC) and 7 healthy control subjects (control).



Figure 4. Measuring Blood Flow rate in a diabetic foot with a wound.


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