6
Pergamon J PII: SO306-4565(97)00022-3 rherm. Eiol. Vol. 22, No. 4/5, pp. 275-280. 1997 !D 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0306-4565197 $17.00 + 0.00 HEAT ACCLIMATION IN TELEMETRY EQUIPPED RAT CANDACE B. MATTHEW US Army Research Institute of Environmental Medicine. Kansas St., Natick, MA 01760-5007, U.S.A. (Received 7 March 1997; accepted in revised form I I June 1997) Abstract-In rats with radio-telemetry units, core temperature (Tc), heart rate (HR), and blood pressure (BP) were measured during 2 weeks of heat acclimation and a subsequent heat stress test to differentiate between acclimation and handling effects. Heat acclimated telemetry equipped rats (THAC) had significantly lower HR, systolic BP, and Tc during heat stress than non-acclimated telemetry equipped rats (TCAC). THAC and TCAC rats had greater endurance times and lower water loss rates than comparable groups without telemetry. Differences in resting Tc previously attributed to acclimation may be due to a reduction in sensitivity to stress of handling and measurement of rectal temperature in heat acclimated animals. 0 1997 Elsevier Science Ltd. All rights reserved. Key Word Index: Telemetry; heat; acclimation; thermoregulation; rats; animal; handling stress INTRODUCTION A great deal of individual variability exists in tolerance to high environmental temperatures (Ep- stein, 1990). Intolerant individuals are more likely to suffer heat exhaustion or heat stroke during exposure to high ambient temperatures or while working in more moderate temperatures (Epstein, 1990). Re- peated exposure to a hot environment elicits physiological adaptations which increase tolerance to heat stress. When tolerance occurs as a result of protracted residence in a natural hot climate, it is termed acclimatization. A similar physiological state can be achieved under experimental conditions during acute exposure to a hot environment, often with exercise, for 5 or more days and is termed acclimation (Kolka, 1993). While humans rely on evaporation of sweat for evaporative cooling (Hassanein et al., 1992), rats spread saliva over their ventral surfaces for evaporative cooling when they become hyperthermic (Hainsworth, 1967). Although there is individual variability in heat tolerance and ability to acclimate, the following are among the physiological changes generally observed with acclimation in both man (Wenger, 1988) and rats (Gordon, 1990; Horowitz et al., 1983; Horowitz and Meiri, 1993; Horowitz and Samueloff, 1988): INCREASES IN plasma volume, tolerance time in the heat, skin blood flow, time interval during which sweating (saliva spreading in core temperature; heart rate; blood pressure; rats) can be maintained; DECREASES IN core temperature (Tc) during heat exposure, Tc threshold for sweating (salivation), and heart rate (HR) during heat exposure. Core temperature (Dilsaver and Majchrzak, 1990; Morley et al., 1990; Vidal et al., 1983) and HR (Guiol et al., 1992) are both increased by the handling and/or restraint usually required to measure these variables in the rat. Further, some of the specific pathogen-free rats currently supplied by breeders may have an exaggerated hyperthermic response to experimental stress (Matthew et al., 1996). The use of radiotelemetry implants (requiring no handling of the animals following surgical implantation) for measurement of blood pressure (BP) and HR has been validated using both pressure transducers and direct arterial cannulation (Bazil et al., 1993; Morley et al., 1990). Likewise, temperatures measured with the telemetry implants are comparable to those obtained with rectal probes (Dilsaver et al., 1992). Telemetry was also used to determine the relative contributions of voluntary activity, ambient tempera- ture, and drinking and their interaction on the dose-response hyperthermia induced by 3,3-methylenedioxymethamphetamine administra- tion (Dafters, 1995). This study was designed to examine the effects of heat acclimation on HR, Tc, and.BP in telemetry equipped rats. Additionally, Tc and water loss are compared in telemetry and non-telemetry equipped acclimated rats. 275

Heat acclimation in telemetry equipped rat

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Page 1: Heat acclimation in telemetry equipped rat

Pergamon

J

PII: SO306-4565(97)00022-3

rherm. Eiol. Vol. 22, No. 4/5, pp. 275-280. 1997 !D 1997 Elsevier Science Ltd. All rights reserved

Printed in Great Britain 0306-4565197 $17.00 + 0.00

HEAT ACCLIMATION IN TELEMETRY EQUIPPED RAT

CANDACE B. MATTHEW

US Army Research Institute of Environmental Medicine. Kansas St., Natick, MA 01760-5007,

U.S.A.

(Received 7 March 1997; accepted in revised form I I June 1997)

Abstract-In rats with radio-telemetry units, core temperature (Tc), heart rate (HR), and blood pressure

(BP) were measured during 2 weeks of heat acclimation and a subsequent heat stress test to differentiate

between acclimation and handling effects.

Heat acclimated telemetry equipped rats (THAC) had significantly lower HR, systolic BP, and Tc

during heat stress than non-acclimated telemetry equipped rats (TCAC).

THAC and TCAC rats had greater endurance times and lower water loss rates than comparable groups

without telemetry.

Differences in resting Tc previously attributed to acclimation may be due to a reduction in sensitivity

to stress of handling and measurement of rectal temperature in heat acclimated animals. 0 1997 Elsevier

Science Ltd. All rights reserved.

Key Word Index: Telemetry; heat; acclimation;

thermoregulation; rats; animal; handling stress

INTRODUCTION

A great deal of individual variability exists in

tolerance to high environmental temperatures (Ep-

stein, 1990). Intolerant individuals are more likely to

suffer heat exhaustion or heat stroke during exposure

to high ambient temperatures or while working in

more moderate temperatures (Epstein, 1990). Re-

peated exposure to a hot environment elicits

physiological adaptations which increase tolerance to

heat stress. When tolerance occurs as a result of

protracted residence in a natural hot climate, it is

termed acclimatization. A similar physiological state

can be achieved under experimental conditions

during acute exposure to a hot environment, often

with exercise, for 5 or more days and is termed

acclimation (Kolka, 1993).

While humans rely on evaporation of sweat for

evaporative cooling (Hassanein et al., 1992), rats

spread saliva over their ventral surfaces for

evaporative cooling when they become hyperthermic

(Hainsworth, 1967). Although there is individual

variability in heat tolerance and ability to acclimate,

the following are among the physiological changes

generally observed with acclimation in both man

(Wenger, 1988) and rats (Gordon, 1990; Horowitz

et al., 1983; Horowitz and Meiri, 1993; Horowitz and

Samueloff, 1988): INCREASES IN plasma volume,

tolerance time in the heat, skin blood flow, time

interval during which sweating (saliva spreading in

core temperature; heart rate; blood pressure;

rats) can be maintained; DECREASES IN core

temperature (Tc) during heat exposure, Tc threshold

for sweating (salivation), and heart rate (HR) during

heat exposure.

Core temperature (Dilsaver and Majchrzak,

1990; Morley et al., 1990; Vidal et al., 1983) and HR

(Guiol et al., 1992) are both increased by the handling

and/or restraint usually required to measure these

variables in the rat. Further, some of the specific

pathogen-free rats currently supplied by breeders

may have an exaggerated hyperthermic response to

experimental stress (Matthew et al., 1996). The use of

radiotelemetry implants (requiring no handling of the

animals following surgical implantation) for

measurement of blood pressure (BP) and HR has

been validated using both pressure transducers and

direct arterial cannulation (Bazil et al., 1993; Morley

et al., 1990). Likewise, temperatures measured with

the telemetry implants are comparable to those

obtained with rectal probes (Dilsaver et al., 1992).

Telemetry was also used to determine the relative

contributions of voluntary activity, ambient tempera-

ture, and drinking and their interaction on

the dose-response hyperthermia induced by

3,3-methylenedioxymethamphetamine administra-

tion (Dafters, 1995). This study was designed to

examine the effects of heat acclimation on HR, Tc,

and.BP in telemetry equipped rats. Additionally, Tc

and water loss are compared in telemetry and

non-telemetry equipped acclimated rats.

275

Page 2: Heat acclimation in telemetry equipped rat

276 C. B. Matthew

METHODS AND MATERIALS

Animals

All experimental procedures were approved by our

Institute Animal Care and Use Committee and

carried out with adherence to the ‘Guide for the Care

and Use of Laboratory Animals’, as revised in 1996.

Adult male Sprague-Dawley (CD’, Charles River

Labs, Kingston. NY, 400-500 g) Rattus norvegicus

were used; female rats were not used in these studies

because of the effect of the estrous cycle on body

temperature. Rats were divided into four groups:

CAC (N = 24, control), HAC (N = 24, heat accli-

mated), TCAC (N = 6, telemetry equipped, control).

and THAC (N = 6, telemetry equipped, heat

acclimated).

Telemetry implants

Transmitters (Data Sciences, St. Paul, Minnesota,

cat# TLI lM2-C50-PXT) were surgically implanted in

the abdominal cavity. These sensors measure physical

activity, Tc, BP, HR, and biopotential (in this case

ECG). Signals from the implants were received and

analyzed using DATAQUEST IV software on an 386

PC equipped with and OS2 operating system (Data

Sciences).

Surgery

Rats were anesthetized with sodium pentobarbital

(50 mg kg ‘, ip and given atropine 400 ug kg ‘, im).

Telemetry transmitters were implanted aseptically as

follows: A mid-ventral incision was made and the

descending aorta exposed between the renal arteries

and the iliac bifurcation. The BP cannula was

introduced into a micro-incision just anterior to the

iliac bifurcation and advanced toward the renal

arteries; the cannula was fixed in place with tissue

adhesive and a dacron patch. The temperature probe

attached to the implant was sutured to the abdominal

wall just lateral to the transmitter body placement,

The two ECG leads were run through stab wounds

in the abdominal muscle wall, tunneled subcu-

taneously with a trochar to the Lead II configuration.

and sutured to subcutaneous tissue. The body of the

transmitter was sutured into the abdominal muscle

wall closure through the holes for that purpose in the

tab on the transmitter body. Following surgery, 10

days were allowed to ensure complete recovery prior

to heat acclimation; animals were closely monitored

for food and water consumption and general health

status.

Experimental procedures

Before acclimation, three times a week during

acclimation, and three times a week for two weeks

following the heat stress test BP, HR, Tc, and ECG

were monitored for 60-90 min at the same time each

morning (between 0730 h and 0900 h). Rats were

acclimated for 2 weeks as follows: CAC and TCAC

rats were housed in a chamber maintained at 26°C.

50%rh and HAC and THAC rats were housed at

32-33-C 50% rh. As previously reported (Horowitz,

1976) not all rats are able to heat acclimate; thus, two

rats whose heart rates did not decrease with

increasing duration of heat exposure and whose

weight loss failed to stabilize were not included in the

THAC group.

After acclimation, pairs of rats (CAC and HAC or

TCAC and THAC) were subjected to a heat-stress

test. The animals, while remaining in their home

cages, were placed in a chamber maintained at 415°C

until a Tc of 415°C was attained. The Tc of the CAC

and HAC rats was manually measured by insertion

of a rectal thermistor (#423. Yellow Spring Instru-

ment Co., Inc., Ohio) 6.5 cm beyond the anal

sphincter every 15 min. The TCAC and THAC rats

had Tc, HR, and BP monitored telemetrically every

2.5 min from 30 min prior to heat stress through

30 min after removal from the heat. At the end of the

heat-stress test all the animals were removed to a

26 C chamber to recover.

All values are given as the mean + standard error.

Statistical comparisons between pairs of groups in

Tables 1 and 2 were done using Student’s ‘t’ test. In

Fig. I each point represents the mean of the six

animals in the group at that time; there was no data

averaging over time. Each dependent variable in

Table 1, Heat-stress test: core temperature data (via telemetry in TCAC and THAC. via rectal urobe in CAC and HAC)

Group (N) Pre-heat Tc ( C) Endurance time* (min) Heat rate ( min- ‘) Cool rate (’ min ‘j

TCAC(6) 37.7 f 0.2 334 f 28 .012 f ,001 ,098 f ,020

THAC(6) 37.7 f 0.1 381 f 22 ,010 + ,001 .092 + ,013

CAC(24) 38.6’ + 0. I 223* + I? .015 f ,002 .038? + ,005

HAC(24) 38.1’: * 0.1 218’ + 12 ,016’ + .OOl ,056’: * ,004

Values are mean & standard error.

*Time to reach a Tc of 41.5 C

?Significantly different (P < 0.05) from comparable telemetry group. $ Significantly different from CAC.

Page 3: Heat acclimation in telemetry equipped rat

Telemetry and heat acclimation

Table 2. Heat-stress test: weight loss data

217

Group (N) Pre-heat Wt (g) Water loss* (g) Water loss rate (g min- ‘)

TCAC(6) 493 + 13 58 f 5 .I7 f .Ol THAC(6) 423’ f 11 45” f 4 ,124 + .Ol CAC(24) 487 + 9 41’ f 2 .I9 f .Ol HAC(24) 430: + 7 34’: + 2 .1s: f .Ol

Values are mean f standard error. *Weight loss corrected for fecal pellet production. ‘Significantly different (P i 0.05) from comparable telemetry group. ?&nificantly different from CAC. Significantly different from TCAC.

Fig. 1 was analyzed by group and time using a two

way analysis of variance.

RESULTS

Data in Table 1 indicate that the HAC rats had significantly decreased pre-heat Tc and greater cooling rates than the CAC rats. However, the pre-heat Tc’s and cooling rates of the TCAC and THAC rats were not different. Both telemetry groups had lower pre-heat Tc, greater endurance time, slower rates of rise of core temperature during heat stress, and faster cooling rates after removal from the heat than their non-telemetry equipped counterparts.

Weights of the four groups were not different prior to the start of acclimation (data not shown), but following 2 weeks of acclimation, acclimated rats were significantly lighter than their respective control groups (Table 2). In the HAC and THAC rats there was an initial drop in weight for 2-3 days then a gradual return to and stabilization at the pre-acclim- ation weight; CAC and TCAC rats continued to grow normally. Telemetry equipped rats lost significantly more water at a slower rate (THAC vs HAC but not

TCAC vs CAC, Table 2) during their longer (Table 1) heat exposure intervals than non-telemetry equipped

rats. Heart rate of THAC rats was significantly reduced

from that of the TCAC rats by 3 days of acclimation (287 f 5 vs 319 &- 8 bpm). In Fig. 1 the mean HR, Tc, and systolic BP of all six rats in the TCAC and THAC groups are plotted from 30 min prior to the start of the heat stress until such time as the first rat in each group reached the endpoint Tc of 41.5”C (TCAC = 255 min, THAC = 355 min). Standard error bars are not included to simplify the figure; however the ranges of standard errors for each dependent variable were: HR: + 4 to 17 bpm, Tc: f 0.1 to 0.3”C, and systolic BP: k 1 to 8 mmHg. A two-way analysis of variance by acclimation state and time on the data of Fig. 1 indicated the following:

There are significant differences (P < 0.001) between

acclimated and unacclimated rats during all of the intervals indicated by an asterisk as follows: HR of THAC is lower across the whole interval from - 30 to 255 min, Tc of the THAC is lower from 0 to 90 and from 180 to 255 min, systolic BP of the THAC group is lower from 0 to 255 min). There is a difference by time in Tc from 0 to 90 min and in systolic BP from 0 to 255 min. Diastolic BP (data not shown) was not different between the two groups. There are no significant differences due to the interaction between time and acclimation state. Following the end of heat stress all rats were returned

to an ambient temperature of 26°C and the heart rates of the two groups were no longer different by 2 days post heat stress.

DISCUSSION

The pre-heat Tc (Table 1) of the HAC rats was significantly less than that of the CAC rats. However, TCAC and THAC rats had pre-heat TC’s that were not different from each other but were lower than those of either the CAC or HAC rats. Similarly, Morley et al. (Morley et al., 1990) reported that the apparently higher Tc of hypertensive rats was not different from normotensive rats when the Tc of both groups was measured via telemetry. This suggests

that the hypertensive rats may have simply been more sensitive to the restraint and handling stress necessary for measurement of Tc using rectal probes. Further, Berkey et al. (Berkey et al., 1990) reported that the Tc of telemetry-equipped hypertensive rats remained the same as that of non-hypertensive rats when exposed to an elevated ambient temperature of 35”C, but a further increase to 40°C was sufficiently stressful to result in a significantly higher elevation of Tc in the hypertensive rats.

Likewise, the slower cooling rates of the HAC and CAC rats (Table 1) after completion of the heat stress test could be attributed to the handling and restraint response. Also, the slower cooling rates of the CAC rats may have been augmented by the greater water

Page 4: Heat acclimation in telemetry equipped rat

278 C. B. Matthew

loss of CAC rats (Table 2) and resultant decreased

volume available for peripheral perfusion and

radiative loss on return to the cooler (26°C) ambient

temperature.

Heat acclimation in rats has previously (Horowitz

(‘1 al., 1983) increased endurance time in the heat: 5

days of acclimation resulted in the greatest augmen-

tation. and longer acclimation periods resulted in

significant but diminished endurance advantages. In

the current work there was no difference in time to

reach 41.5”C between the HAC and CAC rats after

14 days of acclimation. Factors that may have

contributed to this difference are that, in the earlier

work, the Tc was measured continuously with an

indwelling rectal probe and the ambient temperature

was lower (40°C). Additionally, the strain of rats used

250

42

38 '?

37 L

180

in the current study have previously been shown

(Matthew ef al., 1996) to have an exaggerated

hyperthermic response to handling which may have

helped to mask the expected increase in endurance.

However, the HAC rats did exhibit the following

significantly different (from CAC) indices of acclim-

ation: lower pre-heat Tc, higher cooling rates, more

efficient evaporative water loss, and hypertrophy of

the salivary glands (HAC = 0.84 + 0.02 mg gland

& ’ body weight vs CAC = 0.69 _+ 0.01).

In this study, HR of the THAC rats was

significantly lower than that of the TCAC rats by 3

days of acclimation and continued throughout the

heat stress. The Tc and systolic BP of the THAC rats

did not diverge from those of the TCAC rats until

after the start of the heat stress. However, the

Start of Heat

- Mean Control, TCAC

Mean Acclimated, THAC I I I I I I I 1 # I I I

* = significantly different

30 60 90 120 150 180 210 240 270 300 330 360 390

Time (minutes)

Fig. 1. The means of the Tc. HR. and systoiic BP for TCAC and THAC (N = 6 group ‘) are plotted

from 30 min before the start of the heat stress through the time that the first animal ofeach group reached a Tc of 41.5 C. *Indicates a significant (P < 0.001) difference between TdAC and THAC for the indicated

time period. Tc measured via telemetry.

Page 5: Heat acclimation in telemetry equipped rat

pre-heat Tc difference between HAC and CAC The views, opinions, and/or findings contained in groups was no longer evident by 30 min of this report are those of the author and should not be heat exposure (CAC = 39.9 f 0.1 “C, HAC construed as official Department of the Army = 39.8 f O.l’C). Again, it appears that the hyper- position, policy or decision, unless so designated by thermia resulting from handling may be greater than other official documentation. In conducting the and mask differences due to acclimation. research described in this report, the investigators

The effect of acclimation on Tc (Fig. 1) was a shift adhered to the ‘Guide for the Care and Use of in the heating curve; the initial elevation to plateau Laboratory Animals’, Department of Health and temperature was delayed by about 60 min and the Human Services, revised 1996. United States Army plateau in Tc indicating sufficient evaporative cooling Research Institute of Environmental Medicine is an was maintained longer in the THAC than the TCAC AAALAC accredited facility and will continue to group. The lower water loss rate of the THAC rats adhere to the standards and requirements thereof. (Table 2) maintained over a longer period of time Citations of commercial organizations and trade (Table 1) seems to indicate a more efficient use of names do not constitute an official Department of the evaporative water loss. The lower weights of the Army endorsement or approval of the products or HAC and THAC rats at the start of heat (Table 2) services of these organizations. are due to the previously reported (Gordon, 1990) decreased food consumption of rats during heat Acknowledgements-The author would Iike to thank SGT’s acclimation. Total weight loss during heat stress was Anthony I. Osagie, DeAngelious Morrison, and Daniel K.

not the limiting factor in determining heat tolerance Navara and MS Kimberly A. Tartarini for their technical

as telemetry-equipped rats lost significantly more support and Dr. Ralph P. Francesconi for reviewing the

water but at a slower rate than the non-telemetry- manuscript.

equipped rats (Table 2). Here again, the absence of handling stress has resulted in more efficient use of

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