Clinical and Experimental Pharmacology and Physiology (1 976) 3, 449-452.

Circulatory changes in cold-acclimation and cold stress

D. T. J. Chiu and K. K. Cheng Department of Physiology, Facctlty of Medicine, Hong Kong University, Hong Kong

(Received 13 October 1975; revision received 9 December 1975)

SUMMARY

1. The cardiovascular changes of conscious cold-acclimated (CA) and warm- acclimated (WA) rats during exposure to 5°C or 28°C were studied.

2. The cardiac output, heart rate and stroke volume of CA rats exposed to 5°C and of WA rats during cold stress were significantly greater, and their calcu- lated total peripheral resistance significantly less than those of WA rats exposed to 28°C. These results show that circulatory changes participate in cold acclimation and cold stress. The circulatory changes in the two conditions were compared and the mechanism of the observed differences were discussed.

3. CA rats exposed to 28°C showed a striking decrease of oxygen consumption and arterio-venous O2 difference, but significant circulatory changes were decreased heart rate and cardiac index only, indicating that the response was mainly metabolic.

Key words : aortic pressure, cardiac output, cold-acclimation, cold stress, oxygen consumption, peripheral resistance, rat.

INTRODUCTION

Studies of the cardiovascular changes in cold exposure were few and conflicting. For in- stance, Heroux (1961) claimed that arterial blood pressure increased in cold-acclimated rats but not LeBlanc (1960), while Evonuk & Hannon (1963) noted that cardiac output did not change in cold-acclimatized rats but Jansky & Hart (1968) showed that it rose in rats adapted to cold.

It was the intention of this study to clarify with the use of a more refined technique the issue of the cardiovascular effect of cold stress and of cold-acclimation in conscious rats.

METHODS

Cold-acclimated (CA) and warm-acclimated (WA) rats were produced by keeping adult male Wistar rats in controlled-temperature rooms at 5°C and 28°C respectively for 6-10

Correspondence: Dr K. K. Cheng, Physiology Department, Hong Kong University, Li Shu Fan Building, Sassoon Road, Hong Kong.

449

450 D. T. J. Chiu and K. K. Cheng

weeks. They were then exposed to either cold (5°C) or warm (28°C) environments, and their cardiac output, oxygen consumption and aortic pressure were measured as described by Chiu (1974). Briefly, the right ventricle was catheterized via the jugular vein and the dorsal aorta via the carotid artery after the rat was lightly anaesthestized with pentobarbitone sodium (30 mglkg, i.p.), and when the rat regained consciousness and moved about, it was placed in the water-tight chamber of a closed-circuit oxygen consumption apparatus. The chamber was immersed in a thermostated water bath at 5°C or 28°C for 0.5 h for stabiliza- tion before the above determinations were made. The tests were, therefore, done about 2 h after the rat had left the controlled-temperature room, but this should not affect the result because the effect of cold acclimation is not lost at room temperature for up to 4 days (Sellers et al., 1951). The total peripheral resistance (TPR), stroke volume, heart rate and arterio-venous 0, difference were calculated from the obtained data as described by Chiu (1974). Data were analysed by standard t-test, and all the reported differences were statisti- cally significant at P<O.O5 and usually at P<O.OOl.

RESULTS

Table 1 summarizes the results. For better appreciation of the physiological differences, parameters of given pairs of experimental groups are compared in whole, as follows.

(1) WA at 28°C v. CA at 5°C (Columns 1 and 3, Table 1) Comparing animals at the temperatures to which they had been previously acclimated

shows that CA rats had a higher cardiac output and index, heart rate and stroke volume than WA rats. There was no significant difference in aortic pressure, and the calculated

TABLE 1. Cardiovascular changes, the oxygen consumption and arterio-venous 0, difference of cold- and warm-acclimated rats exposed to cold and warm environments (n in parentheses)

Warm-acclimated Cold-acclimated

Exposed to 28°C Exposed to 5°C (24) (8)

Mean s.e.m. Mean s.e.m.

Exposed to 5°C Exposed to 28°C (18) (6)

Mean s.e.m. Mean s.e.m.

Cardiac output (ml/min) Cardiac index (l/min/m2) Heart rate (beats/min) Stroke volume (ml/beat) Total peripheral resistance

(mmHg/ml/min) Mean aortic pressure

(mmHg) Oxygen consumption

(ml/min/m2) Arterio-venous oxygen

difference (~01%)

65.0 2-53 128.1 11.43 1.6 0.06 3.1 0.27

0.17 0.007 0.29 0.028 391 7.1 437 10.4

2-23 0.098 1.06 0.059

140 2.3 128 3.8

121.8 3.71 287.1 13.70

7.89 0.109 9.67 0.640

113.3 4 2 8 95.8 8-13 2.9 0.11 2.4 0.22

489 6.9 409 16.1 0.23 0.009 0.24 0.022

1.31 0.075 1.05 0.118

144 4.7 140 4.2

328.5 9.07 177.5 8.28

11.38 0.300 7.62 0.665

Circulatory changes in cold exposure 45 1

TPR was lower in the CA group. Oxygen consumption and arterio-venous 0, difference were higher in the CA group.

(2) (a) WA at 5°C v. WA at 28°C Comparing columns 2 and 1, Table 1, indicates that acute cooling of WA rats increased

cardiac output and index, heart rate and stroke volume. The aortic pressure fell significantly and so did the calculated TPR. The oxygen consumption and arterio-venous 0, difference increased.

(b) WA at 5°C v. CA at 5°C Comparing columns 2 and 3, Table 1, shows the differences between the WA rats when

acutely cooled and the CA rats at the same temperature. The cardiac output and index did not differ significantly, but the cooled WA rats had a larger stroke volume and slower heart rate, with lower aortic pressure, calculated TPR, oxygen consumption and arterio-venous 0, difference.

(3 ) (a) CA at 5°C v. CA at 28°C (Columns 3 and 4, Table 1) Acute warming of CA rats did not significantly affect the cardiac output but decreased

the cardiac index and heart rate. Stroke volume, aortic pressure and calculated TPR did not change significantly. The oxygen consumption and arterio-venous 0, difference were decreased.

(b) CA at 28°C v. WA at 28°C (Columns 4 and 1, Table 1) Acutely warmed CA rats had, when compared to WA rats at the same temperature, a

higher cardiac output and index and stroke volume, without significant difference in the heart rate and aortic pressure. The calculated TPR was lower and the oxygen consumption higher, while the arterio-venous 0, difference did not differ significantly.

DISCUSSION

The greatly increased cardiac output, heart rate and stroke volume with pronouncedly decreased TPR in CA and WA rats exposed to 5°C clearly show that circulatory changes participate in the response of cold acclimation and to cold stress beside the increased metabolic activity. The present result in CA rats is in agreement with findings of Heroux (1961) and of Jansky & Hart (1968), while the discrepant results of LeBlanc (1960) and Evonuk & Hannon (1963) are attributable to their use of anaesthesia which affects the cardiac output (Popovic & Kent, 1964; Jansky & Hart, 1968). The rise of stroke volume and heart rate in cold acclimation and during cold stress is apparently related in part to the activated P-receptor mechanism in prolonged cold exposure (LeBlanc, Vallikres & Vachon, 1972), but the mechanism of the significantly slower heart rate and greater stroke volume in WA rats during cold stress compared to CA rats exposed to 5"C, though their cardiac output did not differ significantly, is not clear.

The greater decrease of the TPR in WA rats during cold stress compared to that in CA rats exposed to cold is at least partly attributable to the more pronounced vasodilatation in skeletal muscle caused by the vasodilator metabolites produced by the thermogenic shivering in cold stress, while in the CA rats the associated non-shivering thermogenesis in the non-

452 D. T. J. Chiu and K. K. Cheng

muscular tissue (Roberts & Smith, 1967; Smith & Horwitz, 1969; Chaffee & Roberts, 1971) should diminish the vasodilator response in skeletal muscle with consequent less fall of the TPR. The significant decrease of aortic pressure in the WA rats during cold stress compared to that of CA rats exposed to cold is obviously related to the associated greater decreased TPR. The greater oxygen consumption and arterio-venous O2 difference in CA rats exposed to 5°C than in WA rats during cold stress may be related to the greater oxygen demand of the hypertrophic organs and tissues in the CA rats (Heroux & Gridgeman, 1958; Ray, Roubicek & Hamidi, 1968). For the same reason, although the arterio-venous O2 difference did not differ, the oxygen consumption of CA rats exposed to 28°C remained higher than that of WA rats exposed to 28°C. The marked reduction of oxygen consumption in CA rats exposed to 28°C with decrease of heart rate and cardiac index only, suggests that the response was mainly a decrease of the adaptively increased metabolic activity of the CA rats (Heroux & Gridgeman, 1958; Hsieh, 1963; Roberts & Smith, 1967) with slight circulatory change only.

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