Is cold acclimation of benefit to hibernating rodents?

The thermal challenge associated with cold acclimation (CA) and hibernation requires effective cardio-respiratory function over a large range of temperatures. We examined the impact of acute cooling in a cold-naïve hibernator to quantify the presumed improvement in cardio-respiratory dysfunction triggered by CA, and estimate the role of the autonomic nervous system in optimising cardiac and respiratory function. Golden hamsters (Mesocricetus auratus) were held at a 12 h:12 h light:dark photoperiod and room temperature (21°C euthermic control) or exposed to simulated onset of winter in an environmental chamber, by progression to 1 h:23 h light:dark and 4°C over 4 weeks. In vivo acute cooling (core temperature Tb=25°C) in euthermic controls led to a hypotension and bradycardia, but preserved cardiac output. CA induced a hypertension at normothermia (Tb=37°C) but on cooling led to decreases in diastolic pressure below euthermic controls and a decrease in cardiac output, despite an increase in left ventricular conductance. Power spectral analysis of heart rate variability suggested a decline in vagal tone on cooling euthermic hamsters (Tb=25°C). Following CA, vagal tone was increased at Tb=37°C, but declined more quickly on cooling (Tb=25°C) to preserve vagal tone at levels similar to euthermic controls at Tb=37°C. For the isolated heart, CA led to concentric hypertrophy with decreased end-diastolic volume, but with no change in intrinsic heart rate at either 37 or 25°C. Mechanical impairment was noted at 37°C following CA, with peak developed pressure decreased by 50% and peak rate-pressure product decreased by 65%; this difference was preserved at 25°C. For euthermic hearts, coronary flow showed thermal sensitivity, decreasing by 65% on cooling (T=25°C). By contrast, CA hearts had low coronary flow compared with euthermic controls, but with a loss of thermal sensitivity. Together, these observations suggest that CA induced a functional impairment in the myocardium that limits performance of the cardiovascular system at euthermia, despite increased autonomic input to preserve cardiac function. On acute cooling this autonomic control was lost and cardiac performance declined further than for cold-naïve hamsters, suggesting that CA may compromise elements of cardiovascular function to facilitate preservation of those more critical for subsequent rewarming.

Cold-impaired cardiac performance in rats is only partially overcome by cold acclimation.

The consequences of acute hypothermia include impaired cardiovascular performance, ultimately leading to circulatory collapse. We examined the extent to which this results from intrinsic limitations to cardiac performance or physiological dysregulation/autonomic imbalance, and whether chronic cold exposure could ameliorate the impaired function. Wistar rats were held at a 12 h:12 h light:dark (L:D) photoperiod and room temperature (21°C; euthermic controls), or exposed to a simulated onset of winter in an environmental chamber by progressive acclimation to 1 h:23 h L:D and 4°C over 4 weeks. In vivo, acute cold exposure (core temperature, T(b)=25°C) resulted in hypotension (approximately -20%) due to low cardiac output (approximately -30%) accompanying a bradycardia (approximately -50%). Cold acclimation (CA) induced only partial compensation for this challenge, including increased coronary flow at T(b)=37°C (but not at T(b)=25°C), maintenance of ventricular capillarity and altered sympathovagal balance (increased low:high frequency in power spectral analysis, PSA), suggesting physiological responses alone were insufficient to maintain cardiovascular performance. However, PSA showed maintenance of cardiorespiratory coupling on acute cold exposure in both groups. Ex vivo cardiac performance revealed no change in intrinsic heart rate, but a mechanical impairment of cardiac function at low temperatures following CA. While CA involved an increased capacity for ß-oxidation, there was a paradoxical reduction in developed pressure as a result of adrenergic down-regulation. These data suggest that integrated plasticity is the key to cardiovascular accommodation of chronic exposure to a cold environment, but with the potential for improvement by intervention, for example with agents such as non-catecholamine inotropes.

Effects of acute and chronic cooling on cardiorespiratory depression in rodents.

The cardiovascular and ventilatory responses of the Wistar rat (a non-hibernator) and the Syrian hamster (a hibernator) to acute and chronic cold exposure were investigated. The acute lowering of core temperature (T(c) = 22 degrees C, hypothermia) compared with normothermia (T(c) = 37 degrees C) and hyperthermia (T(c) = 40 degrees C) was used to examine the underlying differences in the extent of cold adaptation. In euthermic rats, acutely induced hypothermia resulted in a pronounced reduction in heart rate (f(H) reduced by 55%; P < 0.01), a modest but significant elevation of mean arterial blood pressure (mABP increased by 16%; P < 0.05), and a marked reduction in respiratory frequency (f(R) reduced by 64%; P < 0.01). All parameters returned to baseline values on returning T(c) to 37 degrees C, with a modest overshoot on acute hyperthermia. These data are consistent with the depressive effect of low temperature on biological rate functions and increased vagal tone in the cold, while matching f(R) to a lowered metabolic rate (MO(2)). Cold acclimation had little effect on this pattern of response, suggesting that any adaptive increase in thermogenesis is limited. Euthermic hamsters also showed a significant reduction in f(H) on acute cooling (74%; P < 0.01). In contrast to rats, hamsters developed a significant decrease in mABP (52%; P < 0.01) and maintained a relatively high f(R) (4%; n.s.). These data suggest a resetting of the baroreflex and relative hyperventilation, consistent with an elevated MO(2) associated with enhanced nonshivering thermogenesis. Cold acclimation had little effect on thermal sensitivity, though the response curves were displaced to produce a relative hypertension and tachycardia at a given T(c). These data suggest a reduced cardiorespiratory coupling in the hibernator compared with the non-hibernator.

Maintenance of heterogeneity of capillary spacing is essential for adequate oxygenation in the soleus muscle of the growing rat.

OBJECTIVES: Normal muscle growth is accompanied by capillary proliferation, which usually lags behind the increase in muscle size, causing a decline in mean capillary density (CD). It is not known, however, how the capillary distribution is affected and what impact it has on the oxygenation of the muscle. METHODS: The capillarization of soleus muscles of rats (64-425 g) was determined with the method of capillary domains. As well as quantifying CD, capillary to fiber ratio (C:F), and fiber size, this method provides a measure of the heterogeneity of capillary spacing. Capillary locations were used to mathematically model oxygenation levels within the muscle. RESULTS: The increase in muscle mass was largely attributable to 5-fold increase in fiber size, accompanied by a more than 3-fold rise in C:F. The mismatch between rates of angiogenesis and muscle growth resulted in a decrease in CD. However, the heterogeneity of capillary spacing was unaffected (heterogeneity index logRSD: 0.091 +/- 0.013; mean +/- SD) as was muscle PO2, with modal values between 4 and 60 mmHg (0.5 and 8 kPa). CONCLUSIONS: Angiogenesis during normal muscle growth does not maintain CD, but with similar heterogeneity of capillary spacing it preserves the potential for adequate intramuscular oxygenation.

Differing mechanisms of cold-induced changes in capillary supply in m. tibialis anterior of rats and hamsters.

The physiological, metabolic and anatomical adaptations of skeletal muscle to chronic cold exposure were investigated in Wistar rats (Rattus norvegicus), a species that defends core temperature, and Syrian hamsters (Mesocricetus auratus), which may adopt a lower set point under unfavourable conditions. Animals were exposed to a simulated onset of winter in an environmental chamber, progressively shortening photoperiod and reducing temperature from 12 h:12 h L:D and 22 degrees C to 1 h:23 h L:D and 5 degrees C over 4 weeks. The animals were left at 4 degrees C for a further 4 weeks to complete the process of cold-acclimation. M. tibialis anterior from control (euthermic) and cold-acclimated animals of similar mass showed a significant hyperactivity-induced hypertrophy in the rat, but a small disuse atrophy in the hamster. Little evidence was found for interconversion among fibre types in skeletal muscle on cold-acclimation, and only modest differences were seen in activity of oxidative or glycolytic enzymes in either species. However, adjustments in Type II fibre size paralleled the muscle hypertrophy in rat and atrophy in hamster. Cold-induced angiogenesis was present in the rat, averaging a 28 % increase in capillary-to-fibre ratio (C:F) but, as this was balanced by fibre hypertrophy across the whole muscle, there was no change in capillary density (CD). In contrast, the C:F was similar in both groups of hamsters, whereas CD rose by 33 % in line with fibre atrophy. Within distinct regions of the m. tibialis anterior, there was a correlation between angiogenesis and fibre size in rats, in which oxygen diffusion distance increased, but not in hamsters, in which there was a reduced oxygen diffusion distance. Consequently, the change in C:F was greatest (39 %) in the glycolytic cortex region of the m. tibialis anterior in rats. We conclude that non-hibernator and hibernator rodents improve peripheral oxygen transport following cold-acclimation by different mechanisms. In rats, an increase in fibre girth was accompanied by a true angiogenesis, while the improved apparent capillary supply in hamsters was due to smaller fibre diameters. These responses are consistent with the strategies of resisting and accommodating, respectively, an annual fall in environmental temperature.