Effect of changes in local skin temperature on postural vasoconstriction in man

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1 Clinical Science (1 988) 74, Effect of changes in local skin on postural vasoconstriction in man AHMAD A. K. HASSAN AND J. E. TOO= Department of Physiology, Charing Cross and Westminster Medical School, London (Received 24 March/l3 July 1987; accepted 29 July 1987) SUMMARY 1. The effects of locally induced alterations in skin on the postural changes in skin blood flow of the foot were assessed in 38 healthy subjects in a constant environment (22 k 0.5"C, mean * SD). 2. Moderate local cooling and warming of the foot (2636 C) was induced by blowing cold or hot air. Higher ranges of (3844 C) were achieved by a thermostatically controlled disc heater. 3. Skin blood flow was measured before and during each change in local skin using a laser Doppler flowmeter with the foot maintained at heart level, and placed passively 50 cm below the heart. Blood flow was measured in two skin areas: (i) the dorsum of the foot, where arteriovenous anastomoses are absent, and (ii) the pulp of the big toe, where these anastomoses are relatively numerous. 4. It was found that within the physiological range of 2636 C the normal postural fall in foot skin blood flow was preserved, whereas it was markedly attenuated or totally abolished at higher s (3844 C). The pattern of response was quite similar in areas having or lacking arteriovenous anastomoses. 5. It is suggested that the failure of postural vasoconstriction observed at the higher skin s might contribute to some of the problems of cardiovascular adaptations seen in a hot environment. Key words: arteriovenous anastomoses, laser Doppler flowmetry, posture, skin blood flow, skin, thermoregulation. Abbreviations: D, dependent; H, horizontal. Correspondence: Dr J. E. Tooke, Postgraduate Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter EX2 5DW, U.K. INTRODUCTION The thermoregulatory function of the cutaneous circulation is largely mediated by changes in skin blood flow in response to changes in core, skin or the of the environment [l]. It has been suggested that the arteriovenous anastomoses that are concentrated in acral regions, by producing large variations in flow, could facilitate this thermoregulatory role [2]. The effects of local on the skin circulation are physiologically relevant since the skin is exposed to a greater range of than any other organ in the body except, perhaps, the upper part of the alimentary tract [3]. The responses of the cutaneous vasculature as a whole to localized changes serve to assist body regulation by vasoconstriction to moderate cold stimuli and vasodilatation to warm ones [4]. Changes in local skin could also influence transcapillary fluid movement, as it has been shown that raising local skin is accompanied by a rise in capillary hydrostatic pressure [5] and capillary filtration rate [6]. Lowering the foot below heart level is associated with a reduction in foot blood flow thought to be mediated mainly by precapillary vasoconstriction in response to the increased hydrostatic pressure in the dependent position [7, 81. It has been suggested that the mechanism of this postural increase in precapillary resistance might involve a local sympathetic axon reflex [9] or a myogenic response [lo]. By limiting the rise in capillary hydrostatic pressure and by reducing blood flow on dependency, the postural vasoconstrictor response could act to reduce oedema formation in the upright posture [9, lo]. The influence of changes in skin on the posturally induced vasoconstriction is still unclear. However, in a previous study from this laboratory [ l l], during indirect heating in man (resulting mainly in centrally elicited thermoregulatory vasodilatation), the postural vasoconstrictor response was shown to be markedly

2 202 A. A. K. Hassan and J. E. Tooke attenuated in skin areas rich in arteriovenous anastomoses, and preserved in areas lacking these anastomoses. The aim of the present study was to investigate the effect of locally induced alterations in skin on the postural changes in skin blood flow in the human foot. METHODS Subjects Experiments were performed on 38 lightly clad healthy adult subjects (31 males and seven females), aged 2370 years, after 20 min of adaptation in a controlled room at an ambient of 22 * 0.5"C and at least 2 h after the last food, drink or smoking. All subjects gave their informed consent to the study, which was approved by the local Ethical Committee. Measurement of the postural changes in skin blood flow The postural changes in foot skin blood flow were measured using a laser Doppler flowmeter (Periflux, MK VII; Perimed, Stockholm, Sweden). A full description of the principle of this method has been given previously [ 1 I]. In brief, this noninvasive technique utilizes the Doppler shift of laser light backscattered from moving erythrocytes in the cutaneous microcirculation. The output voltage signal produced has been shown to be linearly related to the product of erythrocyte concentration and velocity in the measuring volume [12]. In recent years, a good correlation has been shown between laser Doppler flowmetry and many of the conventional techniques used to assess peripheral blood flow including 13"e clearance [ 131, venous occlusion plethysmography and thermal clearance [ 141, and the direct technique of dynamic capillaroscopy [15]. Also, when the flowmeter was used on the pulp of the toes, the recorded flow signals were found to closely parallel the changes in toe volume measured simultaneously by strain gauge plethysmography [ 161. Moreover, we have recently compared the flow values recorded by laser Doppler flowmetry with capillary blood flow velocity measured by television microscopy in the toe nailfold. A strong positive correlation was found between the two techniques when flow was measured in the horizontal (r = 0.979, P< ) and sitting (r= 0.899, P< 0.01) position [ 171. To test for the reproducibility of the method, a separate study was conducted on six male subjects aged 2237 years. Repeated measurements of rest flow from the same skin area (dorsum of the foot or pulp of the big toe) produced coefficients of variation of for flows measured at heart level and % for flows measured 50 cm below the heart. In the present study, the laser output voltage flow signal was recorded on a chart recorder. Measurement of skin and body s Skin was measured continuously on the recording site using a thermocouple of an electronic thermometer (Comark Electronics Ltd, Littlehampton, Sussex, U.K.). Oral was also measured before and during each change in local skin using a standard mercury clinical thermometer. Induction of changes in local skin The postural changes in skin blood flow were recorded first at a skin of 3VC, then during application of moderate local cooling and warming by blowing cold or hot air currents from a hair dryer to achieve skin s of 28, 26 then 32, 34 and 36 C. Higher ranges of skin (3844 C) were achieved using a thermostatically controlled discshaped heater (3 cm in diameter) supplied by the manufacturers with the laser Doppler flowmeter. However, in preliminary experiments, this heater was inadequate to achieve skin s above 42"C, and for this purpose a specially constructed heater was used [ 161. Repeat tests were also performed on six subjects to check for reproducibility of the experimental results at each change in local skin. In six subjects, the postural changes in flow were recorded again after spontaneous cooling of the heated skin area. In order to show whether central reflex effects are involved in the changes in flow after changes in the local of one foot, in 12 experiments skin blood flow was simultaneously measured on anatomically identical skin sites in the contralateral foot using another laser Doppler flowmeter. Study protocol The experimental design consisted of measuring foot skin blood flow with the subject lying horizontal first with the feet maintained at heart level for at least 2 min, then with one foot placed passively 50 cm below the heart (with the rest of the body staying horizontal) for at least 4 min. The mean flow values were planimetrically calculated from the tracings obtained during the 2 min in the horizontal (H) and during the fourth minute in the dependent (D) positions and expressed in arbitrary units (mv). The percentage ratio of dependent flow relative to horizontal flow (D/H) was calculated to show the magnitude of the postural change in flow. So, the lower the ratio the higher the magnitude of postural vasoconstriction and vice versa. In preliminary experiments, this ratio was found to be more reproducible with repeated measurements than the absolute values of dependent flow, with coefficients of variation of '/0. Recordings were made during each change in local skin on two skin areas: (i) the dorsum of the foot, an area where arteriovenous anastomoses have been shown to be absent, and (ii) the plantar surface of the big toe, where these shunt vessels are relatively numerous [2]. After each change in local skin, 1015 min were allowed for the flow to attain a new steady level before the postural changes in flow were assessed. Statistical analysis All results are expressed as m eansk~~~. Because the same skin area was studied throughout the experiment

3 Local and postural vasoconstriction 203 and the data obtained were found to be normally distributed, the paired ttest was used to compare mean flow values obtainedat and below heart level at any given skin. The effects of posture and of local skin (as well as their interactions) on skin blood flow were assessed by twoway analysis of variance. Multiple comparisons between rest flows (at 30 C) and flows obtained at higher or lower s were made using Dunnett's test [18]. RESULTS Analysis of variance revealed a significant effect of both posture and skin on skin blood flow (P= 1.8 X and P=2.8 X for the dorsum of the foot, and P= 2.5 x and P=4.6 X for the pulp of the big toe respectively) as well as a significant interaction between and posture on flow (P= and P= respectively). Dorsum of the foot At skin s of 2636"C, despite a gradual increase in flow measured at heart level with increasing, when the foot was lowered 50 cm below the heart, the flow fell significantly at each tested (Fig. 1). This maintenance of postural vasoconstriction despite rising skin (within the physiological T nl " L n=6 n=19 Skin ("C) Fig. 1. Effect of local changes in skin on the postural changes in skin blood flow (SBF) measured on the dorsum of the foot. 0, At heart level; n, 50 cm below the heart. Results are means with bars indicating SEM. n, Number of experiments. Statistical significance: *P< 0.02, **P< 0.01, ***P< as compared with mean flow values measured at heart level.

4 204 A. A. K. Hassan and J. E. Tooke Table 1. Effect of local skin on the postural changes in foot skin blood flow, expressed as the ratio of dependent flow (D) to horizontal flow (H) Results are means f SEM. n, Number of experiments for each skin site. Statistical significance (Wilcoxon's rank sum test): *P<O.O5, tp<0.01 as compared with mean values at 30 C, the starting resting. n Skin D/H (%) ("C) Dorsum of Pulp of the the foot big toe 26 39f f f f4* * 4* f8t f81 18f4 25f5 28f5 29f3 29f4 27f4 72 f f 7t 140f 121. range) is emphasized by the relative constancy of the ratio of dependent flow relative to horizontal flow (D/H) illustrated in Table 1. With further skin heating to 3840 C, the flow measured at heart level rose significantly (P< 0.001). Although there was still a significant fall in flow on dependency (Fig. l), the marked rise in D/H (Table 1) indicated partial attenuation of the normal postural ' response. At higher skin s (4044"C), the horizontal flow was greatly increased (P<O.OOl) but the postural fall in flow was completely abolished, as indicated by a significantly higher flow in the dependent position (Fig. 1) and a D/H ratio exceeding 100% (Table 1). Plantar surface of the big toe An almost similar pattern of response was found (Fig. 2 and Table 1). Thus the postural vasoconstrictor response was maintained at 2636"C, partially attenuated at 3842 C and totally abolished at 4244 C. However, the mean flow values measured in the toe pulp both in the horizontal and dependent positions were about 312 times higher than the corresponding values measured on the dorsum of the foot (Figs. 1 and 2). There was no significant change in body during the course of any of the experiments performed. Repeat tests in six subjects showed quite reproducible D/H and low coefficients of variation (Table 2). After return (spontaneous cooling) of the heated area to resting skin, the postural vasoconstrictor response was restored. On the dorsum of the foot the D/H was 20.5 k 4.2% after spontaneous cooling as compared with 22.5f3.8% before heating. On the plantar risa lzki B L I I t n=6 n=19 Skin ("C) Fig. 2. Effect of local changes in skin on the postural changes in skin blood flow (SBF) measured on the plantar surface of the big toe. 0, At heart level; m, 50 cm below the heart. Results are means with bars indicating SEM. 12, Number of experiments. Statistical significance: *P< 0.02, **P< 0.01, as compared with mean flow values measured at heart level. T

5 ~~ Local and postural vasoconstriction 205 Table 2. Reproducibility of the postural changes in foot skin blood flow expressed as the ratio of flow measured in the dependent position (D) to flow measured in the horizontal position (H) before (skin 2731 C) and during local heating in six healthy male subjects Skin ("(3 Results are means f SEM. n, Number of experiments. Dorsum of the foot (n = 6) Pulp of the big toe (n = 6) D/H (%) Mean D/H (%) Mean coefficient coefficient 1st test 2nd test of variation (%) 1st test 2nd test of variation (%) ~ ~~ 2731: 28f5 29f f4 22f f 6 30f f5 36f f7 54f f7 70f f14 117f f5 82f f8 120f f12 136fll 1.9 surface of the big toe the corresponding values were 18.2 f 3.2% and 19.8 f 3.5% respectively. It was also observed that the increased flow after local heating in one foot (159f23%, n=4) was not accompanied by any significant change in flow in the contralateral foot (4.7 * 0.2%), whereas the reduction in flow after moderate local cooling in one foot (55 f4%, n = 8) was almost always accompanied by a concomitant, although less marked, fall in flow (27 f 2%) in the contralateral foot, indicating the involvement of a central reflex effect. DISCUSSION This study has confirmed the relationship between local skin and skin blood flow previously reported using venous occlusion plethysmography [ 191. More importantly we have demonstrated that the postural reduction in foot skin blood flow was maintained throughout a physiological range of skin of 2636"C, whereas it was markedly attenuated at 3840 C and totally abolished at or above 42 C. Indeed, at this skin blood flow was higher in the dependent than in the horizontal position. Mechanisms of changes in flow after changes in local Because room and body s did not show any significant change throughout the experiments, the observed changes in skin blood flow after local cooling or heating are likely to be attributable to locally induced changes in skin. The changes in flow after local cooling or heating are believed to be mainly mediated by local mechanisms, as they are unaffected by sympathetic and somatic denervation [20, 211. However, in the present study local cooling of one foot resulted almost instantaneously in a concomitant, but relatively less marked, reduction in flow in the contralateral foot, indicating that the response to cold represents a summation of local effects and a centrally elicited reflex effect [22]. The nature of the local mechanisms underlying the changes in flow produced by changes in local is uncertain but direct effects of heat on the vascular smooth muscle [23] and changes in blood viscosity [24] are likely to be involved. Postural vasoconstriction during local changes in skin The mechanisms underlying the reduction in skin blood flow when the foot is placed in the dependent position appear to be fully operative over a wide range of skin (2636 C). In contrast, the marked attenuation or abolition of postural vasoconstriction at higher skin s (above 37 C) suggests an impairment of these mechanisms and could be explained by a heatinduced inhibition of the response of vascular smooth muscle to sympathetic nerve impulses or to circulating catecholamines [25271; the increased flow measured in the dependent position during local heating at 42 C could be ascribed to a passive distension of the cutaneous vascular bed in response to the postural increase in the local hydrostatic and transmural pressures. It is unlikely that the failure of postural vasoconstriction during local heating above 42 C is related to a thermal injury of the vascular bed as the postural response was completely restored after spontaneous cooling. It is likely that the high blood flow associated with local heating has a useful protective effect: by carrying heat away from the heated area, it reduces the below the skin surface and the likelihood of thermal damage [3]. The pattern of the postural vasoconstrictor response at any given skin was quite similar in skin areas with or without arteriovenous anastomoses. This is in contrast to the findings obtained during indirect heating where the partial release of the sympathetic vasoconstrictor tone was accompanied by a marked attenuation of postural vasoconstriction in the toe pulp yet preservation of the response in the dorsum of the foot [l 11. This discrepancy between the effects of direct and indirect heating is best explained by the observations that arteriovenous anastomoses are more sensitive to central thermoregulatory reflexes than to influences of local skin [28,29]. On exposure to a thermal stress, the combined effects of the attenuated vasoconstrictor response in areas rich in

6 206 A. A. K. Hassan and J. E. Tooke arteriovenous anastomoses (by increased core and release of sympathetic vasoconstrictor tone) [ 111, and the failure of the response in areas with and without anastomoses (by the local effect of heat) when the skin exceeds the physiological range, could result in displacement of a considerable amount of blood in the dependent extremities (venous pooling) with a subsequent fall in central blood volume, cardiac filling pressure, stroke volume and cardiac output [30]. This could partially explain the postural syncope (orthostatic intolerance) on standing in the heat [30, 311. In addition, the failure of the postural increase in precapillary resistance and the subsequent increase in flow in the dependent limbs at extremely high skin, together with the rise in capillary hydrostatic pressure [5] and capillary filtration rate [6], might contribute to the swelling of the extremities commonly observed in a hot environment. ACKNOWLEDGMENTS We thank Professor L. H. Smaje for his continuous support, and Mrs Alison Allen for typing the manuscript. A.A.K.H. was supported by an Egyptian Government Scholarship and J.E.T. by the Wellcome Trust. REFERENCES 1. Spealman, C.R. (1945) Effect of ambient air and of hand on blood flow in hands. American JournalofPhysiology, 145, Grant, R.T. & Bland, E.F. (1931) Observations on arteriovenous anastomoses in human skin and in the bird's foot with special reference to the reaction to cold. Heart, 15, Greenfield, A.D.M. (1963) The circulation through the skin. In: Handbook of Physiology, vol. 11, Circulation, pp Ed. Hamilton, W.F. American Physiological Society, Washington, D.C. 4. Hellon, R.F. (1963) Local effects of. British Medical Bulletin, 19, Levick, J.R. & Michel, C.C. (1978) The effects of position and skin on the capillary pressures in the fingers and toes. 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