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- near-infrared spectroscopy
- oxygen consumption measurement
- muscle metabolism
- rhythmic isometric exercise
Near-infrared spectroscopy (NIRS) is a direct, non-invasive optical method for measuring local oxygenation and haemodynamics in muscle tissue. Although measurement of local oxygenation by NIRS has been used for the diagnosis of metabolic myopathies, the technique has not previously been applied to inflammatory myopathies. Dermatomyositis is a muscle disorder characterised by complement mediated capillary necrosis, resulting in ischaemia and hypoperfusion. We have now employed NIRS to study the effect of corticosteroid treatment on haemodynamics in muscle tissue in dermatomyositis.
The pathological features of dermatomyositis are characterised by a decreased number of capillaries per muscle fibre and necrosis of single muscle fibres or clusters of fibres at the periphery of the fasciculi.1 Muscle fibre regeneration and an increased number of capillaries have been shown in dermatomyositis after intravenous immune globulin treatment,2 but corticosteroids are still considered to be the first line of therapy. In the clinical setting, the effect of treatment is mainly assessed by muscle strength and creatine kinase (CK) levels. Direct measurement of capillary and muscle fibre status can only be done by repeated muscle biopsies. However, apart from the fact that muscle biopsies are invasive, they are also a static representation of muscle tissue at a fixed time point and at a particular location (selection bias).
This is the first time that NIRS, a non-invasive optical method for the measurement of oxygenation and haemodynamics in muscle tissue, has been used to study the effect of treatment in a patient fulfilling the clinical and histological criteria of definite dermatomyositis.3 A young woman from Aruba, aged 24 years, presented with subacute erythema of the facial skin and severe proximal muscle weakness (arm muscles: mean Medical Research Council (MRC) grade 3; leg muscles: MRC grade 2). Serum CK levels were slightly increased (220 IU/l). Five weeks after the onset of symptoms, treatment with corticosteroids was started in our department at a dose of 60 mg/day (for six weeks), the dose being subsequently tapered. CK levels decreased and muscle strength increased (arm muscles: MRC grade 4; leg muscles: MRC grade 3) in week 12.
Tissue oxygenation was measured by NIRS immediately before treatment was begun and again after three and seven weeks of treatment. NIRS is based on the relative tissue transparency to light in the near-infrared region, and on the oxygen dependent absorption changes of haemoglobin and myoglobin. Using a modification of the Lambert–Beer law, in which physical path length is incorporated to account for light scattering, it is possible to calculate quantitative values for oxygen consumption and blood flow in skeletal muscle. NIRS is non-invasive and measures oxygenation directly in the muscle. Moreover, it is relatively inexpensive, easy to apply, and applicable at the bedside.
In this study, NIRS measurements were obtained using a continuous wave near-infrared spectrophotometer (Oxymon, Biomedical Engineering Department, University of Nijmegen, Netherlands). Using this spectrophotometer, which generates light at 905, 850, and 770 nm, it is possible to differentiate between oxyhaemoglobin/myoglobin (O2Hb/O2Mb) and deoxyhaemoglobin/myoglobin (HHb/HMb). The optical fibres were placed on top of the flexor digitorum superficialis muscle in the same location for all the measurements. Data were sampled at 10 Hz.
Quantitative NIRS values for oxygen consumption (mV̇o2) were calculated by evaluating the rate of decrease in [O2Hb] during arterial occlusion, as previously described.4 Reoxygenation rate (ΔO2Hb) was determined as the rate of initial increase in O2Hb measured over three seconds immediately after cessation of arterial occlusion. Both mV̇o2 and ΔO2Hb were calculated at rest and following rhythmic isometric handgrip exercise at various work intensities. Each exercise session consisted of one minute of exercise at a contraction rate of 30/min (50% duty cycle), immediately followed by 45 seconds of arterial occlusion for the calculation of mV̇o2 and ΔO2Hb. Whereas mV̇o2 is a measure of mitochondrial function at a certain work insentity and is dependent on the vascular capacity of oxygen delivery, ΔO2Hb reflects the initial recovery rate at which deoxygenated haemoglobin/myoglobin are resaturated.5 It is therefore directly related to microvascular function. All measurements were performed at the same absolute work intensities.
Figure 1 shows the effect of corticosteroid treatment, measured non-invasively and with relative ease by NIRS, in the patient with severe dermatomyositis. Before treatment was begun, resting mV̇o2 was slightly higher than in healthy controls (0.19 v 0.14 ml O2/min/100 g, respectively). However, mV̇o2 during exercise was about 60% lower than in the controls over the whole range of exercise intensities (fig 1A). After three weeks of treatment, mV̇o2 had already markedly increased. After seven weeks, mV̇o2 had increased even further and was now only 25% below that of the controls, and within the normal range at several work intensities. Serum CK levels were normalised, while muscle strength had increased. ΔO2Hb (fig 1B) showed similar results, with slow recovery rates before treatment was begun and an increase over all work intensities at the three week and seven week examinations. ΔO2Hb after seven weeks of treatment exceeded the normal mean value.
As NIRS measures local oxygenation and haemodynamics within the muscle, it can give direct insight into the working microvascular system. ΔO2Hb increased during treatment, indicating an increase in capillary function. As a result of the increased capillary function and a possible regeneration of muscle fibres, muscular oxygen availability increased, enhancing oxidative capacity—as reflected by the increase in local muscle oxygen consumption.
Although a muscle biopsy will remain indispensable for the diagnosis of dermatomyositis, NIRS is an interesting and non-invasive tool for monitoring the effect of treatment non-invasively and with relative ease. While both serum CK levels and muscle strength are indirect measures, and muscle biopsies provide only a static fingerprint of the muscle, NIRS measures local microvascular and mitochondrial function directly in the intact and working physiological setting.