Altered control of skin blood flow at high skin and core temperatures.

JOURNAL OF APPLIED PHYSIOLOGY Vol. 38, No. 5, May 1975. Prinled

Altered high

in U.S.A.

control

of skin blood

flow

at

skin and core temperatures C. R. WYSS, G. L. BRENGELMANN, J. M. JOHNSON, L. B. ROWELL, IIepartments of Physiology and Biophysics and of Medicine and School of Nursing, University of Washington School of Afedicine, Seattle, Washington 98195

WYSS, C. R., G. L. BRENGELMANN, J. M. JOHNSON, L. B. ROWELL, AND I>. SILVERSTEIN. Altered control of skin bloodflow at high 1975.skin and core temperatures. J. Appl. Physiol. 38(5) : 839-845. Five subjects were studied during periods of controlled increases and decreases in skin temperature (T,) over the T, range of 3440°C. One protocol was designed to observe changes in forearm blood flow (FBF) and heart rate (HR) with changes in core temperature (T,; right atria1 blood temperature and esophageal temperature were measured) with T, held constant at two levels. FBF and HR changed linearly with T, in the T, range of 37-38OC with T, constant at 38OC. A second protocol imposed T, changes at two levels of T, and T, ; this protocol also included a prolonged cooling period. The influence of T, on FBF and HR was reduced when T, changes occurred at an elevated T, and Tc , and FBF showed considerable hysteresis during cooling. We conclude that a linear model for the control of FBF or HR is inadequate as a tool for predicting the control of these variables. temperature circulation;

regulation; heat stress;

thermoregulatory heart rate; forearm

models; blood flow

peripheral

WHAT EXTENT does a quantitative description of any thermoregulatory control mechanism depend upon the protocol used to obtain the data? The literature on control of sweat rate (SR) and skin blood flow (SkBF) includes both linear and nonlinear models (5, 8, 14, 15, 18). These models were derived from experiments which may not have been specifically designed to reveal properties (e.g., existence of thresholds) incorporated into the equations used to describe the behavior of the effector in question. For example, in our recent work on SkBF (18), based on measurements of forearm blood flow (FBF) in heated men, linear regression analysis was used to determine relative roles of skin temperature (T,) and internal temperature (T,)l in the control scheme. This sort of ad hoc quantitative approach may have the bad effect of suggesting that the model implicitly assumed represents how the system actually works. Several observations suggest that linear models are, in fact, inadequate as predictors of thermoregulatory behavior. First, the best fit equations describing the control of FBF and heart rate for successive, but different heating protocols show significant differences (18). Second, SkBF can remain elevated after prolonged heating even though TO

l The designation T, is used for nonspecific reference tures at internal thermosensitive sites, e.g., hypothalamus cord.

to temperaand spinal

AND

D. SILVERSTEIN

T, and T, return to control levels (13). Third, the behavior of FBF as a function of T, can be dependent on the previous heating or exercise history of the subject on any given day (6). Fourth, the model would predict that, during periods of constant T,, a simple linear regression of FBF versus T, should yield the same calculated sensitivity of FBF to changes in T, (cy) as that a calculated with a multiple regression analysis during periods of changing T,; but there can be disagreement between values of a calculated by the two methods (6). Since this latter discrepancy occurs over a range of T, where FBF rises linearly with T, (18), an important nonlinear T, influence in the control of SkBF is suggested. In the present study, we set out to test the validity of specific features in our previous linear model (18). Our previous protocol contained periods wherein T, and T, were highly correlated; this could have obscured nonlinear contributions of T,. Therefore, we designed one protocol to include an upward step in T, from an elevated level after prolonged heating at constant T,. This protocol was intended specifically to reveal any altered T, sensitivity at elevated T, and T,. This protocol was also designed to challenge another implicit characteristic of most current models: freedom from hysteresis, i.e., will the system retrace its steps on return to a previous value of T, and T,? We designed a second protocol to study influence of T, at two levels of constant T,. Although our experiments were not specifically designed to study the control of SR, we have included this variable in our analysis where possible. PROCEDURES

AND

METHODS

General. The subjects were five men aged 23-26 yr. Each was given a thorough physical examination and found to be in good health. The subjects gave their informed consent after being fully acquainted with all experimental procedures and after institutional review of the project. The study consisted of two parts, performed on separate days. The preparatory procedures for part I (4 subj) were identical to those for part 11 (5 subj) except that right atria1 blood temperature (Tra) was measured only in part II. After being fitted with heart rate and T, leads, the subject was dressed in a water-perfused suit used to control T, (12). Temperature probes were inserted into the esophagus to left atria1 level and into the right atrium (part 11 only) using previously described techniques (11). All studies were

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840

WYSS

ET

AL.

Ts* "C

40r

AVERAGE

39

,m

To,,

=c

r

r

HR,

bpm

80601

I

FBF,

I

I

I

1

ml/l00ml~min

3Qr

I

I

FIG. 1. Typical results from part I (subj SF). Average body skin temperature (average T,, top panel) was held constant at 38 and 4O’C. Note: I) esophageal temperature (T, $, second panel) reached 39°C but heart rate (HR, third panel) and forearm blood flow (FBF, fourth panel) ‘did not level off; 2) sweat rate (SR, jijth panel) 1eveled off at 55 min; 3) close correspondence between rise in FBF and HR and rise in T,, with average T, constant at 38 “C (15-55 min) ; 4) local temperature at Whitney gauge (local T,, top panel) did not exceed 37°C; and 5) neither HR nor FBF returned to control levels when average T,, local T,, and T,, had done so at 70 min.

minutes

conducted with subjects in the supine posture. One forearm was fitted with a mercury-in-Silastic strain gauge of Whitney’s design (16) ; the suit covered the gauge but was held away from it by a wire cage placed around the arm. The other arm was prepared for measurements of SR as previously described (18). Measurements of heart rate, FBF, SR, T,, T,,, and esophageal temperature (T,,) were made throughout each study; techniques for making these measurements have been described (2, 12, 18). In addition, during part Z, T, of the forearm (local T8) was measured on a spot next to the Whitney gauge with a bead thermistor taped to the skin under the wire cage. As before (18) we have used T,, as a measure of T, where possible because under dvnamic conditions T,, is a rapidly responding measure of T, (9, 18). T,, was measured in each subject for comparison with T,, as a measure of T,. We have used total FBF as an index of changes in SkBF based on evidence that during heating at rest muscle blood flow either remains unchanged or decreases slightly (3,4, 10). Part I. The experimental protocol for part I is illustrated in Fig. 1. After a 5- to IO-min control period with T, held at a level considered thermally neutral by the subject, T, was rapidly increased to 38°C and held at this level (for 30-45 min) until T,, began to level OK Thereafter, T, was rapidly increased to 40°C held there until T,, reached approximately 39°C and then rapidly reduced to below control levels.

We chose this protocol for two reasons. First, it contained a long period of constant T, at 38°C for an analysis of T, influences unencumbered by changes in T, or Ts. Second, T, was raised to a level almost 1 “C higher than reached in our previous study, thus allowing an examination of any “roll off” or saturation in responses to changes in T,. Part II. The protocol for part II is illustrated in Fig. 3. After a control period like that described above for part I, T, was rapidly increased to 37.5”C and held there until SR had been elevated above insensible levels for several minutes (20-30 min after start of heating). T, was then increased as rapidly as possible towards 40°C and not reduced until T,, reached approximately 38°C (5-8 min). T, was then rapidly reduced to 37.5”C and held there until both T,, and T,, had been stable for several minutes. Finally T, was rapidly lowered to control levels or below and held there until T,, and T,, had returned to control values. The rationale for this protocol was that abrupt changes in T, at two levels of T, and T, would provide a dissociation between T, and T, changes, and thus allow a separate analysis of their effects on SkBF in two distinct regions of the “T,-T, plane”. The protocol was designed to restrict changes in T, to a range previously investigated by us (18) in which we observed an approximately linear relationship between changes in SkBF and T,. This restriction freed us from having to deal with two possible nonlinear relationships simultaneously. Further, the extension of the period of cooling in


SKIN

BLOOD

FLOW FBF,

CONTROL ml/lOOml~min

AT

HIGH

BODY

841

TEMPERATURE

12Or

HR. bpm

SR, mg/cd.min I

OL Tes, FIG. 2. FBF (left panels), HR (center panels), and SR versus T,, for control and heating portions ofpart 1 (e.g., in Fig. 1) in s&j SF (top panels) and subj BH (lower panels). lines for FBF and HR are regression lines for two periods T,. Arrows below lines delimit data included in regression

(right

panels)

up to 62 min Solid straight of constant with T, con-

this protocol allowed an examination of the influences of T c and T, as the system returned to its control state following a period of heating. RESULTS

Part I. In part I we examined the behavior of FBF, heart rate, and SR as functions of T, at two levels of constant T,. FBF and heart rate rose linearly with respect to T, up to 38°C with T, held constant at 38°C. Figure 1 illustrates a typical response to the part I heating protocol. Although T,, exceeded 39°C in some subjects, neither heart rate nor FBF leveled off; thus the response of these variables does not saturate within this range of T,,. The SR response did level off in all subjects at levels of T,, between 37.9 and 38.3”C. Figure 2 shows FBF, heart rate, and SR plotted against T,, for two subjects during the control and heating portions of part I. As noted previously (18) both FBF and heart rate were approximately linearly related to T,, while T, was constant at 38°C. But at a constant T, of 40°C the sensitivity of FBF to a change in T,, was reduced by about 10-l 5 % while the sensitivity of heart rate was reduced by 25-50 % in different subjects, indicating that a) high T, depressed a! or 6) a! becomes a function of the level of T, with T, above 38°C. In either case, the above observations indicate that over the full range of T, and T, observed in part I, a linear description of the control of FBF, heart rate or SR is not adequate.

OC

1

I

37

30 Tes

8

39

stant at 38°C; arrows above lines delimit data with T, constant at 40°C. r Coefficients for regressions with T, at 38°C always exceeded 0.90 (average 0.96). Sensitivity of FBF and HR to changes in T,, (i.e., CY, slopes of regression lines) was reduced at higher levels of T, and T,,. SR response saturated in both subjects. Part II. This part of the study shows that T, does have an altered influence in the control of SkBF and heart rate when changes in T, occur at elevated levels of T, and Tc, and that the control of these variables is not free of hysteresis. The influence of T, on FBF and heart rate is reduced when T, and T, are elevated above normal levels. The influence of both T, and T, on FBF and heart rate is reduced as these temperatures fall from elevated levels (these results are summarized in Table 2). Figure 3 illustrates results from part II for one subject. At the end of the study FBF was elevated above control levels (13 vs. 4 ml/100 ml per min) even though T,,, T,,, and T, were all below control levels; this elevation was observed in three of the five subjects. The same results were seen at the end of Part I in all subjects (see Fig. 1). Clearly, the control of FBF deviates markedly from that gredicted by a linear model during periods of cooling; FBF exhibits marked hysteresis. Often heart rate as well was still elevated slightly above control levels at the end of cooling (Figs. 1 and 3). The initial rise in heart rate and FBF while T,, was depressed after the start of the first T, step in Fig. 3 indicates a T, and/or + T, influence on these variables; this was seen in all subjects. The sharp rise in heart rate at the start of the second T, increase (at 36 min) also indicates a T, and/ or +T, influence on heart rate when T, and T, were elevated; this increase was seen in all subjects. A rise in FBF similar to that seen for heart rate was never observed at the start of the second T, increase.


842

WYSS

Period

A

I

--

Period

ts, .C/

+2

Ts,

Period

I B

ET

AL.

1

C I

min

.C

40

36

FIG. 3. Results from part II (subj GS). T, (second panel) was increased, then decreased in two steps. Bars

HR, 100

at top of figure show time periods used for data analysis (see text and Table 2). Period A always extended from start of study up to second increase in T,; period B begins where right atriai blood temperature (Tra, third panel) started to rise above control and ends at second decrease in T,; period C begins at start of first decrease in T,, lasting to end of experiment. Rate of change of T, (Ts) is in top panel and T,, is in T,, panel. Note T,, lags behind Tra. HR, SR, and FBF are solid lines in lower three panels. FBF and HR fail to return to control levels at end of study. Dashed lines in HR, SR, and FBF panels show results of fitting a linear equation to the data; note dashed lines for HR and FBF stop at end of period B (see text and Table 1). Multiple correlation coefficients for HR, SR and FBF regressions were 0.98, 0.97, and 0.98, respectively, in this subject.

bpm

-

80-

60, o8

r

0.4

SR,

1

I

I

L IO

20

I

mg/cm2.min

-

FBF,

3or

ml/l00ml~min

1

1 30 minutes

I 40

1 50

1 60

1. Average results of regressions for part 11 for J;ve subjects ~ -__------._ .- -..-~- p--____--_______-

TABLE

.-

Equations with T,., as a measure of Tc FBF = 10.62 [O.lg]t(T,, - 36.5) + 0.55 [.05]t[T, - 33.0) + 0.59$[.25]t(+T,)* HR = 22.39 [0.34] (T,, - 36.5) + 3.05 [.lO] (T, - 33.0) + 4.08 [.50] (+T,)* SR = 0.91 [.Ol] (T,, - 36.5) - 0.05 r.0051 (T, - 33.0) + 0.14 r.021 c+T,)* Equations with T,, as a measure of Tc FBF = 9.81 [.16] (T,, - 36.5) + 1.05 [.04] (T, - 33.0) + 0.47$[.23] (+?‘,)* HR = 20.27 [.35] (Tes - 36.5) + 4.13 [.lO] (T, - 33.0) + 3.40 [.56] (+?,)* SR = 0.74 [.Ol] (T,, - 36.5) + 0.08 [.003] (T, - 33.0) + 0.14 [.03] (+T,)*

I?

-

2.40 [.25]t(-Ts)” - 4.34 [.51] (-T&* - 0.15 [.Ol] (-‘i?s)*

-

1.67 [.22] (-Ts)* 2.61 [.56] (-T,)* 0.09 [.Ol) (-T,)*

-

4

-

.ll + 52.0 - 0.10

0.97 0.98 0.98

19.3 7.34 - 18.0

3.26 + 45.6 - 0.66

0.98 0.97 0.97

9.34 4.91 9.25

Equations for FBF and HR are the average results of regressions performed from start ofperiod A to the end of period R (Fig. 3). Equations for SR are average results of regressions performed when SR was above insensible levels (e.g., 32-71 min in Fig. 3). R is the average multiple correlation coefficient. cr/@ is the ratio of regression coefficients for the T, term (CX) and T, term (/3). * The term within the parentheses is set equal to zero if negative. t The term within the brackets is the standard deviation of the mean value calculated as follows: [ ] = dZvar(bJ/N, where var(bi) is the variance of an individual regression coefficient, and N is the number of subjects aver$ Average regression coefficient so labeled is not significantly different from zero at a 95yo confidence level. aged.

In order to assess the influence of T,, T,, -j-T, and -TS in various periods of part 11, we applied a multiple linear regression analysis similar to that reported previously (18). As before, +T, and -T, were treated as separate variables.

In our previous analysis we imposed a threshold for influence of T, for empirical reasons (i.e., to maximize chance of seeing any role of T,). In the present study, were testing specific aspects of a linear model; thus, we

the the we did


SKIN

BLOOD

FLOW

CONTROL

AT

HIGH

BODY

not impose any thresholds since that would have introduced an arbitrary assumption of specific non-linear behavior into the analysis. All regressions were performed against T, and +TS during heating periods or -TQ T,, CT ra or Td, during cooling: periods. Table 1 shows average results of fitting the data of part II to a linear model. Data from the second cooling step were not included in the analysis for FBF and heart rate because of the obvious hysteresis exhibited by FBF during this period (see above). The model is shown explicitly in the equations of Table 1. The linear regressions result in a close empirical fit to the data (see Fig. 3 and the values of R in Table 1). This does not indicate, however, that the model assumed in the analysis necessarily represents the operation of the svstem. For example, the values of R in Table 1 are impressively large both for the equations with T,a and for those with T,, as a measure of T,. Yet it is clear that at least one of these temperatures is not a good measure of T, since their behavior differs significantly during critical periods when T, is changing rapidly (Fig. 3). Use of T,, as a measure of T, predicts a larger role of T, in the control of all variables (note the a/P values in Table 1); this is a result of the lag in T,, behind T,a (9, 18) ( see Fig. 3). The results from all subjects were very similar to the average results shown in Table 1. Table 2 represents a specific test of the model in Table 1. If the model shown in Table 1 correctly described the control of FBF and heart rate then one would expect to find no significant differences between the results of regressions over periods A, B, or C (defined in Fig. 3). Table 2 demonstrates

TABLE 2. Average results of regressions ouer restricted time periods of part II ..-^-~ -_-- .Variable

Time Period

a

P

A~_

a+ --~.

FBF

A

12.1

t FBF

B

11.0

t FBF

C

4.30

t HR

A

25.9

t HR

B

22.4

t HR

C

17.6

[0.63]* = 19t [0.18] = 60

0.98

t -0.50

t

[.lO] = 4.9

[0.73] = 5.9

0.02

[1.43] = 18

3.18

CO.401 = 55

1.93

t t t

1.15 [.24]* t = 4.8t 1.06

t

[.50] = 2.1

[.18] = 0.1

2.16

t 0.55

t

[.12] = 27

5.55

[.22] = 8.9

5.05

t t

[.21] = 10 [.16] = 3.3

[.59] = 9.5 [1.04] = 4.9

4.04

t

[.52] = 7.8

1.46 [.32] 1.23 [.34] t = 4.6 t = 3.6 ~.-__--_-_----Average results are shown for FBF and heart rate (HR) for regressions performed over three time periods as defined in the legend of Fig. 3. The average regression coefficient of the T,, term is cu; P is the average regression coefficient of the T, term, and a+ and 6are, respectively, the average regression coefficients of j-T, and -TT,. The units of a and p are ml. (100 ml)-r~min-r.°C-l for FBF and beats-minel* ‘C-1 for HR. The units of a+ and a- are ml (100 ml)-‘. ‘C-1 for FBF and beats/ “C for HR. * The term for SD in brackets is calculated as in Table 1. t The average regression coefficient shown is significantly different from zero at a 9570 confidence level if t is greater than 2.8.

t

l

[1.40] = 13

[.05]* = 18t

843

TEMPERATURE

38

1 2:Obse;

FBF;

I

0’ Influences on FBF,

of Tc ml/100ml

1 8

I

I

Ts min True

Tc

I

/

I2

6

0 -20

IO

20

30

40

minutes

FIG. 4. Results of linear analysis of FBF control when T, influences are nonlinear. Top panel illustrates typical changes in T, and core temperature (T,) (5, 17, 18). Supposing that solid lines in bottom panel are true influences of T, and T,, then observed FBF will be as shown in second panel (i.e., T, influence is a times the change in Tc, and T, influence is P times change in T, up to a T, of 37°C; T, influence is nonlinear, i.e., it is assumed to be constant at higher T,). Dotted and dashed lines in bottom panel show T, and T, influences on FBF which would be calculated from these data using multiple linear regression. Error in calculated a! exceeds 40% because analysis assumes T, influences are linear (i.e., assumes effect on FBF of changing T, from 37 to 40°C equals effect of changing T, from 34 to 37°C).

that this condition is not met; in particular, note the significant2 reduction in the sensitivity of the effecters to T, changes (p) during period B (high T, and T,) as compared to period A (control T, and T,). Thus the value of ,6 for FBF in Table 1 (with T,a as T,) is an underestimate of the ,6 seen during period A and an overestimate of the P calculated for period B. Table 2 is further evidence that during heating at rest FBF and heart rate rise approximately linearly with T, up to a T,a of 38°C. There is a significant2 reduction in calculated sensitivity of the effecters to changes in T,, (a) between periods A and B, but this reduction is only 10 76. The results of regressions for period C in Table 2 quantify the hysteresis mentioned earlier. Both cy and ,6 are significantly reduced for FBF and heart rate during cooling, reflecting the failure of these variables to return fully to control when T, and T, had done so (Figs. 1 and 3). The results of regressions performed over other time periods are consistent with those shown in Table 2 (i.e., all regressions including the second heating step show a smaller ,6 than those over the first T, step and all regressions including the second cooling step show decreased a and P) . 2 The values of average regression coefficients in Table 2 were assumed to be normally distributed variables with standard deviations as given within the square brackets. If this assumption is made then values of 6 for FBF and heart rate between periods A and B are significantly different (P < 0.0001).


WYSS

844 DISCUSSION

These studies reveal two major findings: I) T, influences both SkBF and heart rate in a nonlinear manner over the temperature range studied, and 2) the control of SkBF exhibits marked hysteresis. In light of the close empirical fit to the data achieved by assuming a linear model (see Table 1 and Fig. 3) one might dismiss the observed nonlinear T, influence as an insignificant effect. In fact, this observation has serious implications for any application of a linear model in studying the control of SkBF. Figure 4 illustrates how a large error can be made in the calculation of Q! by assuming linear control of SkBF in the face of a nolinear T, influence on SkBF. The hysteresis observed in the control of SkBF indicates that the linear model as shown in Table 1 is fundamentally inadequate as a description of the control of SkBF. Clearly, at least one driving variable is missing in the model. This variable could be time, direction of change of T,, and/or deep body temperatures which lag behind T,, and T,, (e.g., rectal temperature (11, 12)). It is also possible that the model as it stands includes all of the relevant variables but lacks a term describing the recent history of the system, e.g., a time integral of some function of T, and T,. Others have observed similar nonlinear behavior of SkBF during periods of cooling. One group (7, 17) has reported a prolonged

40

FBF,

FIG. 5. Result of using a linear model generated from data of Part 11 for s&j GS (Fig. 3) to predict his HR, FBF, and SR during part I. Symbols and layout are as in Fig. 1 except for inclusion of predicted values of effector variables (dashed lines) in three lower panels. Equations used to generate dashed lines were beet-fit linear equations from part II for this subject using T,, as a measure of T, (see text and Table 1).

ml/l00ml~min

\\ I

AL.

elevation in the amplitude of forearm photoelectric plethysmograph pulses after a period of heating, and Wenger et al. (15) show a sustained elevation of FBF during a period of rapidly falling T,, after exercise. Rowe11 (13) has reviewed other observations of this phenomenon. The hysteresis observed in the control of heart rate (see RESULTS and Table 2) could be secondary to the relative depression of peripheral resistance attending hysteresis in the control of SkBF (i.e., arterial blood pressure often falls during rapid cooling (11)). The crucial test of any model is its ability to predict responses in situations not used to derive the data on which the model is based. In order to apply this test we have used the linear equations generated with data from individual subjects in part I1 (see Table 1 for the averages of these equations) to predict the behavior of FBF, heart rate and SR during part 1 in the same subjects; Fig. 5 illustrates a typical result. These tests directly reflected the results of this study as follows: I> agreement between observed and predicted values of FBF and heart rate was best during a period of unchanging T, with T, in the range of 37 to 38°C; 2) heart rate was more accurately predicted by the linear model than FBF during periods of changing T,, reflecting the more linear nature of the T, influence on heart rate (see Table 2); and 3) the model fails completely during the period of cooling due to the hysteresis exhibited by both FBF and heart rate.

IO0 r----JH

ET

I

I

1

1

I

I

\\

S R, mg/cm2.min

3u

4v

minutes


TEMPERATURE

845

As illustrated in Fig. 5 observed and predicted values of SR were in poor agreement. This result is surprising in light of reports that a linear model provides a good description of the control of SR (8). Although local T, was not held constant in these studies (it rose slowly to 37°C) we believe that the calculated sensitivity of FBF to changes in T, (Tables 1 and 2) results largely from neurogenic and not local factors for the following reasons. a) Local T, lags body T, (see Fig. 1) leading to a poor correlation between the two temperatures during the critical period when T, is changing from one level to another; thus any local effects on FBF would have the wrong time course to explain the results. b) Also, the FBF response to local T, is a lagging one (1) leading to further lack of correlation between any responses to local T, versus whole body T,. c) Finally, changes in local T, were too small to account for the observed changes in FBF (raising local arm T, to 37-38°C requires very long periods to effect even small changes in FBF (1). During this study and our previous work, our subjects have shown consistent -responses to heating at rest. The responses can be empirically described assuming linear influence of and additive interaction of input temperatures (Table 1). However, when these assumptions are examined in detail we find tha.t the influence of T, in the control of

SkBF and heart rate is a function of the level of T, and/or T, during heating. Also, the influence of both T, and T, in the control of these variables is reduced when T, and T, are dropping from elevated levels as compared to their influence when rising from normal levels. Thus, a linear equation accurately describing one set of data will not accurately predict the data from a different occasion and a different protocol. The practice of using linear descriptions of the control of thermoregulatory effector variables (8, 14, 15, 18) has value in assessing the average relative influence of controlling temperatures, but this approach can obscure the underlying complexities of the temperature regulating system.

SKIN

BLOOD

FLOW

CONTROL

AT

HIGH

BODY

We gratefully acknowledge the assistance of Mrs. Evelyn C. Steen, R.N., and Mr. Michael McKeag. This work was supported by National Heart and Lung institute Grants HL-09773 and HL-16910. A part of this study was conducted through the Clinical Research Facility of the University of Washington supported by National Institutes of Health Grant RR-37. C. R. Wyss was supported by National Heart and Lung Institute Grant HL-05889 and National Institute of General Medical Sciences Grant GM-00260. J. M. Johnson was supported by National Heart and Lung Institute Grant HL-16910. D. Silverstein was supported by National Heart and Lung Institute Grant HL-0528 1- 15. Received

for

publication

9 October

1974.

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Neural control of human skin blood flow.

Skin temperatures at the nape in infants at high altitude.

Plasma norepinephrine concentration during submaximal and maximal exercise at lowered skin and core temperatures.

Effects of skin blood flow and temperature on skin--electrode impedance and offset potential: measurements at low alternating current density.

Effects of caffeine on skin and core temperatures, alertness, and recovery sleep during circadian misalignment.

Control of skin blood flow during exercise: thermal and nonthermal factors.

Considerations for the measurement of core, skin and mean body temperatures.

Monitoring of core temperature through the skin: A comparison with esophageal and tympanic temperatures.

Blood hyperviscosity with reduced skin blood flow in scleroderma.

Patterns of reinnervation and blood flow in split-skin grafts.

Three-dimensional interactions of mean body and local skin temperatures in the control of hand and foot blood flows.

Thermoregulatory heat production in man: prediction equation based on skin and core temperatures.

Capillary blood flow to the skin of forearm in cirrhosis.

Skin response to histamine dry skin prick test: influence of duration of the skin prick on clinical parameters and on skin blood flow monitoring.

Does activity affect residual limb skin temperatures?

Altered core and skin temperature responses to endurance exercise in heart failure patients and healthy controls.

Changes in human skin blood flow by hyperthermia.

Endothelin reduces blood flow in experimental skin flaps.

A laser Doppler scanner for imaging blood flow in skin.

Acetylcholinesterase inhibitor, pyridostigmine bromide, reduces skin blood flow in humans.

Influence of different durations of electroacupuncture stimulation on skin blood flow and muscle blood volume.

Changes in mouse blood pressure, tumor blood flow, and core and tumor temperatures following nembutal or urethane anesthesia.

Cerebral blood flow at high altitude.

The regional differences in the contribution of nitric oxide synthase to skin blood flow at forearm and lower leg sites in response to local skin warming.