University Department of Anaesthesia and Intensive Care, University Hospital and City Hospital, Nottingham, UK*Corresponding author: University Department of Anaesthesia and Intensive Care, Queens Medical Centre, Nottingham NG7 2UH, UK
The preliminary results of the study were presented to the Anaesthetic Research Society during Oxford meeting, July 2000, and abstracts were subsequently published in the British Journal of Anaesthesia.
Accepted for publication: February 22, 2002
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Abstract |
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Methods. Ten healthy male volunteers were studied. A custom-made perspex iontophoresis chamber was attached to the anterior aspect of the distal forearm; this chamber allowed simultaneous administration of drugs by iontophoresis and measurement of skin blood flow flux by the laser Doppler probe. The flow flux signal, measured in volts, was continuously recorded onto a paper chart recorder. Three control transient hyperaemic response (THR) tests were performed by releasing the manual occlusion of the brachial artery maintained for 20 s. Thereafter, 2% sodium nitroprusside was iontophoresed using a current of 100 mAmp for 240 s. The THR tests were repeated three more times. From the recordings, baseline blood flow flux immediately before the onset of compression (or F1) and maximum blood flow flux immediately after the release of compression (or F2) were taken for analysis. The THR ratio (THRR) was calculated as: THRR=F2/F1. Average values of F1 and THRR were taken from the tests before and after iontophoresis and a paired t-test was used for analysing the changes.
Results. Nine of the 10 subjects showed a hyperaemic response at the release of compression. Iontophoresis of sodium nitroprusside significantly increased the baseline flow flux from 0.77 (range 0.291.61) to 1.88 V (0.732.91). It also completely abolished the THR in all subjects; THRR decreased from 1.65 (1.002.78) to 1.00 (0.981.03).
Conclusion. A brief compression of the brachial artery results in a significant hyperaemic response in the forearm skin; this response is abolished by pre-dilatation of skin vessels. These findings support the hypothesis that the THR test assesses true vasodilatation occurring during arterial compression.
Br J Anaesth 2002; 89: 26570
Keywords: arteries, brachial; complications, vascular reactivity; measurement techniques, transient hyperaemic response
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Introduction |
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In the brain, a transient hyperaemic response (THR) in the middle cerebral artery flow velocity, as assessed by transcranial Doppler ultrasonography, secondary to release of a brief compression (10 s) of the ipsilateral common carotid artery has been used to assess vascular reactivity to the changes in perfusion pressure (cerebral autoregulation).9 10 As compared with the reactive hyperaemia in skin, THR in the brain has been elicited with a much shorter duration of compression (10 s vs >2 min). A similar approach with a shorter duration of ischaemia has not been applied to assess vascular reactivity of forearm skin. However, it may be possible to test vascular reactivity of forearm skin by assessing the changes in flow flux (measured by laser flowmetry) before, during, and after a brief compression of the brachial artery. When compared with the previously described tourniquet method,68 it would have a potential advantage of being simpler, avoiding venous occlusion and, because of a briefer duration of ischaemia, avoiding accumulation of ischaemic metabolites in the tissues.
We hypothesized that a brief compression of the brachial artery would result in vasodilatation in the forearm skin and thus THR upon release of compression. In order to validate that THR represents true vasodilatation, and not a perfusion artefact, we further hypothesized that THR would be absent if the forearm vascular bed was pre-dilated. The aims of this study were to use laser flowmetry to demonstrate the presence of THR following a brief compression of the brachial artery and to study the changes in THR when the vascular bed of forearm skin was pre-dilated by locally iontophoresed sodium nitroprusside.
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Methods |
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The study was undertaken in a quiet room. After a period of acclimatization for 20 min, each subject lay supine and was requested to remain still and quiet for the duration of the study period. One arm was abducted and supported on a pillow at the level of anterior axillary line. A custom-made perspex iontophoresis chamber was attached to the anterior aspect of the distal forearm using double-sided adhesive tape. This chamber was specifically designed to allow simultaneous administration of drugs by iontophoresis and measurement of skin blood flow flux by the laser Doppler probe (Fig. 1). The chamber incorporated two holes; one to house the laser Doppler probe at 90° to the skin, and the other for drug administration. The second hole into which the drug was pipetted contained an inert platinum wire, which was connected to a current generator to serve as cathode during iontophoresis. The anode consisted of an electrocardiogram electrode, which was attached to the forearm 4 cm proximal to the chamber. The chamber was placed distally on the forearm to minimize movement artefacts that could arise when digital pressure was applied to the brachial artery in the anticubital fossa. The flow flux signal, measured in volts, was continuously monitored and recorded onto a paper chart recorder. Skin temperature was measured using a surface probe. On the other arm, non-invasive arterial pressure was measured at 3-min intervals throughout. Change in skin temperature of greater than 0.3°C, and in mean arterial pressure of greater than 10% during the period of study in each volunteer were considered to be significant.
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The THR test was considered suitable for analysis only if there was a sudden and maximal decrease in the flow flux at the onset of compression and if the Doppler signal during compression (biological zero) was stable. As seen in Figure 3, from the recordings of flow flux during a THR test, the following values were taken for analysis: (i) baseline blood flow flux immediately before the onset of compression or F1; and (ii) maximum blood flow flux immediately after the release of compression or F2.
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For analysis, average values of F1 and F2 were taken from the three tests before and the three tests after iontophoresis. The effects of sodium nitroprusside on the baseline flow flux (F1) and THRR were analysed using Students t-test for paired comparison between the values before and those after iontophoresis using Minitab release 10.1.
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Results |
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Discussion |
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Laser Doppler flowmetry (or fluxmetry) is now widely used to study microcirculation in the skin. The red cell flux signal represents a mean from all the vessels within a small region of tissue, the volume of which cannot be measured precisely. The sampling depth is of the order of 12 mm. The major part of the signal derives from the subpapillary vessels, with a smaller part deriving from the capillaries.11 Similar to previous workers,12 we found a wide range of baseline flow flux (0.291.61 V) in healthy volunteers. This variability could be the result of variations in different individuals or inherent variability associated with Doppler signal. Factors that can affect skin blood flow and reactivity include extremes of age, menstrual cycle, temperature surrounding the skin, pigmentation and oedema of skin, skin thickness, mental stress, mental activity, physical exercise, pattern of breathing, nicotine and alcohol, arterial pressure, systemic vasoactive drugs, sympathetic stimulation, and diseases such as diabetes mellitus and Raynauds phenomenon.18 1326 As far as possible, these factors were controlled by the exclusion criteria used in this study and by allowing sufficient period for relaxation before each experiment. Many studies in the past have compared laser Doppler flowmetry to assess skin blood flow with other methods and have shown a close correlation to the xenon clearance technique, photoplethysmography, strain gauge plethysmography, ambulatory venous pressure, digital arterial pressure, and finger skin thermometry.1721 However, comparisons of flow flux are difficult between different individuals or even between different sites within the same individual because of heterogeneity of skin blood flow, localized nature of flow signal and gross variability of microvasculature.14 Thus, there can be a number of reasons why skin blood flow flux shows a high variability between individuals. Despite these limitations, the main advantage of the laser Doppler technique is that it is non-invasive and, when used at the same site, it is sensitive and reliable in assessing changes in flow flux secondary to a variety of stimuli within the same individual.22 Because of this property, it has been extensively used in this manner to assess vascular reactivity.
The hyperaemic response after a brief interruption of blood flow is considered to be a result of local vasodilatation. There are two main mechanisms of reactive hyperaemia,15 that is myogenic vasodilatation caused by pressure and compliance changes within the vessels during the period of interruption in blood flow and accumulation of vasodilating metabolites during occlusion (metabolic theory).
Which mechanism dominates seems to depend on the duration of time of occlusion.15 Myogenic relaxation operates initially (in up to 20 s). However, if circulatory arrest is prolonged, local changes in concentration of oxygen, carbon dioxide, potassium phosphate, adenosine, lactate, kinins, peptides, prostaglandins, and endothelium-derived relaxing factor comprise the metabolic component and reinforce myogenic vasodilatation.15 23 24
In our study the mean value for THRR was 1.65. This would translate into a 65% increase in flow flux during the hyperaemic response. In magnitude, this is much smaller than the approximately 400% increase shown in previous studies.25 26 Also, the duration of hyperaemia in our study, where in all subjects the hyperaemic flow flux returned to baseline within 20 s, was much shorter than that shown in the previous studies in which hyperaemia persisted for several minutes.68 25 26 The main methodological difference between the previous studies and ours is the duration of interruption of blood flow. In the previous studies, circulatory arrest was maintained for time periods varying between 2 and 4.5 min. Circulatory arrest for such a long period of time would provoke both myogenic and metabolic components, while 20 s arterial compression, as in our study, would predominantly provoke the myogenic response only. We believe that a transient response, as seen in the present study, is likely to render the test more suitable for repeated comparisons within an individual as opposed to the tests where hyperaemia persists for several minutes. However, because the hyperaemic response in our study was only very transient, one would tend to wonder whether this was just a reperfusion flux artefact. Such artefacts would be more prominent in high flow situations (i.e. dilated vascular bed). The fact that the hyperaemic response was abolished by pre-dilatation of blood vessels with iontophoresed sodium nitroprusside supports the hypothesis that the hyperaemic response in this study, although very transient, represents true vasodilatation during the period of arterial occlusion and is unlikely to be reperfusion artefact.
The overall range of THRR in the present study was 1.002.78. There are no previous data on THR secondary to a brief duration of compression comparable with our study. However, studies with much longer duration of compression have also shown considerable variability of hyperaemic response with a coefficient of variation of 40%.25 26 Such high variability is probably a reflection of heterogeneity of local circulation and variability of resting vascular tone between different individuals. Our study was not designed to look for the sources of variability in THR. However, further work will be required to fully understand the role of potential variables before the test can be used to study vascular reactivity in patients under anaesthesia and those admitted to intensive care.
Iontophoresis is a well-established technique for transdermal delivery of drugs. It uses a small electric current to drive ions through the skin according to their electrical charge. Combined with measurement of blood flow response by laser Doppler flowmetry, iontophoresis has been used safely and extensively in many studies using vasoactive drugs to look at skin vessel behaviour.3 4 12 Its advantage is that only local effects can be achieved without any systemic side effects. The concentrations used in our study were similar to those described by previous workers, and so was the response. The effect of vasodilatation on THR in the forearm has not been reported previously. We found that once maximal vasodilatation was achieved, the THR response was completely abolished in all subjects. Our results support the hypothesis that under normal conditions brachial artery compression induces vasodilatation within the vascular bed of forearm skin which manifests as hyperaemic response at the release of compression; this response is absent if the vessels are already dilated.
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Acknowledgement |
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References |
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