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18F-2-deoxyglucose deposition and regional flow in pigs with chronically dysfunctional myocardium. Evidence for transmural variations in chronic hibernating myocardium.

BACKGROUND: Hibernating myocardium in patients with collateral-dependent myocardium is characterized by relative reductions in resting flow and increases in the uptake of 18F-2-deoxyglucose (FDG) in the fasting state. We performed the present study to examine whether these key physiological alterations could be produced in a porcine model of chronic coronary occlusion and to assess whether the adaptations consistent with hibernation varied across the myocardial wall. METHODS AND RESULTS: We chronically instrumented pigs (n = 18) with a fixed occluder on the proximal left anterior descending coronary artery (LAD). Three months later, ventricular function, regional myocardial perfusion, and FDG deposition (by excised tissue counting or positron emission tomography) were assessed in pigs after an over-night fast in the closed-chest anesthetized state. Total LAD occlusion with angiographic collaterals was present in the majority of animals. Left ventriculography showed severe anterior hypokinesis, and resting perfusion was significantly reduced in the hibernating LAD region in comparison with the normal remote regions (subendocardium: 0.80 +/- 0.06 versus 1.07 +/- 0.06 mL.min-1.g-1, P < .001; full-thickness: 0.87 +/- 0.04 versus 0.99 +/- 0.06 mL.min-1.g-1, P < .01). There was a twofold increase in full-thickness fasting FDG uptake in the dysfunctional LAD region (1.8 +/- 0.2 by positron emission tomography versus 1.9 +/- 0.1 by ex vivo counting). Ex vivo tissue counting revealed a pronounced transmural variation in FDG uptake in the hibernating region (LAD/normal), which averaged 2.5 +/- 0.2 in the subendocardium, 1.9 +/- 0.2 in the midmyocardium, and 1.4 +/- 0.1 in the subepicardium. CONCLUSIONS: These results demonstrate that pigs instrumented with a proximal LAD stenosis develop hibernating myocardium characterized by relative reductions in resting function and perfusion in association with increased uptake of FDG in the fasting state. The transmural variations in relative resting flow and FDG uptake suggest that myocardial adaptations consistent with hibernation are most pronounced in the subendocardial layers and vary in relation to local coronary flow reserve.

Animals↗

Grafting of nigral tissue hibernated with tirilazad mesylate and glial cell line-derived neurotrophic factor.

Transplantation of embryonic ventral mesencephalon is a potential therapy for patients with Parkinson's disease. As only around 5-10% of embryonic dopaminergic neurons survive grafting into the adult striatum, it is considered necessary to use multiple donor embryos. To increase the survival of the grafted dopaminergic neurons, the clinical transplantation program in Lund currently employs the lipid peroxidation inhibitor, tirilazad mesylate, in all solutions used during tissue storage, preparation, and transplantation. However, the difficulty in obtaining a sufficient number of donor embryos still remains an important limiting factor for the clinical application of neural transplantation. In many clinical transplantation programs, it would be a great advantage if human nigral donor tissue could be stored for at least 1 week. This study was performed in order to investigate whether storage of embryonic tissue at 4 degrees C for 8 days can be applied clinically without creating a need to increase the number of donors. We compared the survival of freshly grafted rat nigral tissue, prepared according to the clinical protocol, with tissue transplanted after hibernation. Thus, in all groups tirilazad mesylate was omnipresent. One group of rats was implanted with fresh tissue and three groups with hibernated tissue with or without addition of glial cell line-derived neurotrophic factor (GDNF) in the hibernation medium and/or the final cell suspension. Earlier studies have suggested that GDNF improves the survival of hibernated nigral transplants. We found no statistically significant difference between the groups regarding graft survival after 3 weeks. However, there was a nonsignificant trend for fewer surviving dopaminergic neurons in grafts from hibernated tissue compared to fresh controls. Furthermore, we show that the addition of GDNF to the hibernation medium and/or to the final cell suspension does not significantly increase the survival of the dopaminergic neurons.

Animals↗

Long-term hibernation of human fetal striatal tissue does not adversely affect its differentiation in vitro or graft survival: implications for clinical trials in Huntington's disease.

Transplantation of human fetal CNS tissue is a promising therapy for neurodegenerative conditions such as Huntington's disease (HD), but its widespread adoption is limited by restricted tissue availability. One method of overcoming this problem would be to store the tissue in hibernation medium, an approach that we reported previously for human fetal striatal tissue stored for up to 24 h. We now demonstrate the feasibility of storing such tissue for up to 8 days in hibernation medium. When either fresh or 8-day hibernated striatal cells were cultured under standard conditions for 4 days, the proportion of DARPP-32-positive neurons did not differ significantly, although the total number of cells was significantly less from tissue that had been hibernated. Six weeks after transplantation into cyclosporin A-immunosuppressed unilateral quinolinic acid-lesioned rats, there was no significant difference between fresh and hibernated grafts, both in terms of graft volume and extent of striatal phenotypic markers. This study therefore clearly demonstrates that hibernation of human fetal striatal tissue for up to 8 days is not deleterious to its differentiation in culture or survival following transplantation, and is therefore an appropriate method of storage for this tissue.

Animals↗

Reversible congestive heart failure caused by myocardial hibernation.

Myocardial hibernation is reversible contractile dysfunction of cardiac myocytes caused by chronic ischemia. Animal studies and observations in human beings suggest that the term hibernation is a misnomer. Repetitive ischemic insult that does not produce necrosis results in functional and histologic tissue deterioration, which culminates in myocyte apoptosis. Revascularization of "hibernating" myocardium results in partial or complete recovery of function, depending upon the duration of ischemia and the severity of cellular degeneration. Improvement in global left ventricular function is proportional to the quantity of hibernating tissue that is revascularized, but this threshold quantity has not been determined with certainty. Diagnostic methods used to detect viable tissue within akinetic left ventricular segments depend upon the recognition of recruitable contractile function or the active concentration of a radioactive tracer. No diagnostic method has shown clear superiority. The most sensitive methods appear to be single-photon emission computed tomographic imaging after reinjection of thallium-201 at 24 hours and positron-emission tomographic imaging with 18F-fluorodeoxyglucose. The most specific diagnostic method appears to be measurement of dobutamine-stimulated contractile function, using either echocardiography or gated magnetic resonance imaging. We present a review of the pathophysiology, diagnosis, and treatment of myocardial hibernation, and include an illustrative case report involving a 57-year-old man with myocardial hibernation.

Angioplasty, Balloon, Coronary↗

Myocardial hibernation. Clinical and pathological perspectives.

Myocardial hibernation refers to a state of persistent regional contractile ventricular dysfunction, in patients with coronary artery disease that is reversible with revascularization. Identification of hibernating myocardial segments is critical for selecting patients who are most likely to benefit from revascularization procedures. Positron emission tomography, thallium scintigraphy, dobutamine stress echocardiography, myocardial contrast echocardiography and magnetic resonance imaging have been extensively used for detection of viable dysfunctional myocardial segments. Although chronic hypoperfusion and repetitive episodes of brief ischemia may play a role in mediating the changes associated with myocardial hibernation the exact pathogenetic mechanisms are not well understood. The structural alterations found in hibernating myocardial segments involve both the cardio-myocytes and the cardiac interstitium. Depletion of contractile elements, loss of myofilaments, disorganization of myocyte cytoskeletal proteins and alterations in adrenergic receptor density have been reported in segments with reversible systolic dysfunction and may cause segmental hypocontractility. In addition, activation of the inflammatory cascade is noted, leading to cytokine and chemokine induction, leukocyte recruitment, interstitial remodeling and fibrosis. Myocardial hibernation represents a part of the spectrum of ischemic cardiomyopathy, which in the absence of a completed myocardial infarction is a dynamic continuous process ultimately leading to irreversible injury and dysfunction. Understanding of the specific molecular signals involved in the pathogenesis of myocardial hibernation is crucial in order to design strategies preventing irreversible dysfunction.

Animals↗

[Stunning, hibernation, and heart failure in patients with coronary disease: crucial role of impaired coronary flow reserve].

Hibernating myocardium can be defined as a chronic, but reversible left ventricular dysfunction that may contribute to congestive heart failure in patients with coronary artery disease. The dysfunction can improve after coronary revascularization and therefore its identification and treatment become central in the management of patients with heart failure secondary to coronary artery disease. Hibernating myocardium can be detected by several techniques (echocardiography performed during the infusion of dobutamine, single photon and positron emission tomography-PET, and magnetic resonance imaging), but none of these techniques can be considered unequivocally superior to the others for the identification of hibernating myocardium. As PET technology has advanced, the noninvasive quantification of absolute regional myocardial blood flow has become possible. The measurement of myocardial blood flow by PET has contributed to the demonstration that transmural blood flow in hibernating muscle is generally within the normal range while the coronary flow reserve is invariably and severely impaired. These findings have contributed to a new pathophysiological theory of hibernation where repetitive ischemia and stunning are considered as the initial mechanisms that might start the process of myocardial hibernation.

Animals↗

Regional 11C-hydroxyephedrine retention in hibernating myocardium: chronic inhomogeneity of sympathetic innervation in the absence of infarction.

UNLABELLED: We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine can identify regional reductions in sympathetic norepinephrine uptake in pigs with hibernating myocardium. However, nonneuronal uptake limited relative differences between regions and would preclude accurate assessment with conventional imaging. We therefore hypothesized that the superior specificity of the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the imaging of regional differences, and we designed this study to determine whether altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional myocardium can be imaged in vivo and to determine the temporal progression and stability of sympathetic dysinnervation in hibernating myocardium. METHODS: Pigs (n = 15) were chronically instrumented with a 1.5-mm stenosis of the left anterior descending coronary artery, a procedure that we have previously shown to produce viable chronically dysfunctional myocardium with reduced resting flow, or hibernating myocardium, after 3 mo. Physiologic studies and HED PET were performed 1-5 mo later with the animals in the closed-chest sedated state. One animal with a myocardial infarct was analyzed separately. RESULTS: After 3 mo, anterior hypokinesis developed (wall thickening, 32% +/- 4% vs. 60% +/- 4%, P < 0.001), with reductions in resting flow (subendocardial flow, 0.81 +/- 0.11 vs. 1.20 +/- 0.18 mL/min/g, P < 0.05) and a critical reduction in subendocardial flow reserve (subendocardial adenosine flow, 0.53 +/- 0.20 vs. 3.96 +/- 0.43 mL/min/g, P < 0.001). Extensive defects in HED uptake were found for hibernating myocardium, with regional retention approximately 50% lower than that in normally perfused remote myocardium (0.035 +/- 0.002 vs. 0.066 +/- 0.002 min(-1), P < 0.001). Relative HED uptake (left anterior descending coronary artery/remote) was lower in chronically instrumented animals than in control animals (n = 4, P < 0.001) and animals studied 1 mo after instrumentation (n = 2, P < 0.05). The regional reduction in sympathetic nerve function was persistent and unaltered for at least 2 mo after the development of hibernating myocardium. CONCLUSION: Hibernating myocardium is associated with persistent reductions in regional uptake of norepinephrine by sympathetic nerves. The inhomogeneity in sympathetic innervation in viable dysfunctional myocardium is similar to that occurring after myocardial infarction and may contribute to arrhythmic death in patients with ischemic cardiomyopathy.

Animals↗

How to discriminate between hibernating and stunned myocardium.

AIM: The aim of the present study was to examine if it is possible to discriminate between hibernating and stunned myocardium in vivo by determining the ratio between diastolic and systolic coronary arterial inflow and by measuring oxygen saturation in draining coronary venous blood. METHODS: Experiments were performed in 32 open chest pigs anesthetized with sodium pentobarbital. In 11 pigs hibernation was induced in a part of the left ventricular myocardium by reducing flow in the mid-left anterior descending coronary artery (LAD) to about 60% of baseline flow. In 12 pigs stunning was induced by occluding mid-LAD twice for 10 min with a 30 min interval. In 9 pigs (control group) coronary flow was not manipulated. RESULTS: We found, at comparable degrees of regional dysfunction, that the ratio between diastolic and systolic flow in stunned myocardium remained unaltered, but fell from about 2 to 1 in hibernating myocardium. Furthermore, coronary venous oxygen saturation decreased from about 30% to 17% in blood draining hibernating myocardium, but remained statistically unaltered in blood draining stunned myocardium. CONCLUSION: We conclude that it is possible to discriminate between hibernating and stunned myocardium by measuring phasic coronary arterial blood flow and oxygen saturation in blood draining the region in question. During hibernation only, the diastolic flow component of coronary arterial inflow is reduced and the coronary venous oxygen extraction increased.

Analysis of Variance↗

Characterization of hibernating and stunned myocardium.

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium ischemia is still ongoing, whereas in stunned myocardium blood flow is fully or almost fully restored. Both the hibernating and the stunned myocardium retain an inotropic reserve. In hibernating myocardium the increase in contractile function is at the expense of metabolic recovery whereas in stunned myocardium no metabolic deterioration occurs during inotropic stimulation. Therefore, inotropic stimulation in combination with metabolic imaging may help not only to identify viable, dysfunction myocardium but also to distinguish hibernating and stunned myocardium. The only causal therapy of hibernating myocardium is to restore blood flow to the hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since by definition blood flow is normal and contractile function will recover spontaneously. If, however, myocardial stunning involves large parts of the left ventricle and thus impairs global left ventricular function, the extent of myocardial stunning can be reduced by inotropic stimulation, without inducing further damage to the myocardium. In the experimental setting, antioxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, most effectively when administered before ischemia.

Adenosine Triphosphate↗

Regulation of ground squirrel Na+K+-ATPase activity by reversible phosphorylation during hibernation.

Maintenance of skeletal muscle energy status during hibernation in ground squirrels, Spermophilus lateralis, was accompanied by a decrease in Na+K+-ATPase pump activity. Energy charge was maintained (0.89) during hibernation at the expense of total adenylates (decreased by 41%). Muscle Na+K+-ATPase activity was 9.1 U/mg protein in euthermic controls but decreased by 60% during hibernation. Enzyme activity was similarly suppressed in vitro when extracts of control muscle were incubated with ATP plus second messengers of protein kinases A, G or C whereas stimulation of protein phosphatases in muscle extracts from hibernators increased Na+K+-ATPase activity. Additional studies confirmed that suppression and reactivation of the enzyme in euthermic muscle extracts can be achieved with protein kinase A and alkaline phosphatase treatments, respectively, and indicated that phosphorylation changes the ATP dependency of the enzyme. Thus, hibernation-induced suppression of Na+K+-ATPase activity in muscle and other organs of ground squirrels, which is a key part of the overall suppression of metabolic rate that constitutes torpor, appears to be regulated via reversible protein phosphorylation.

Adenine Nucleotides↗

Metabolic effects of cold storage on livers from euthermic and hibernating Columbian ground squirrels.

The current study was undertaken to investigate energy metabolism during hypoxia in the cold in livers from euthermic and hibernating Columbian ground squirrels. We hypothesized that the hibernating Columbian ground squirrel would be able to maintain liver energetics for a considerably longer time than euthermic animals. Particular reference was made to the function of glycolysis, which is the only mechanism for energy production under hypothermic ischemia. The transition from aerobic to anaerobic metabolism was apparent in both euthermic and hibernating animals as lactate levels rose within 1-3 h; total lactate accumulation was 2.5 micromol/g in both groups. In euthermic squirrels, liver ATP and ADP decreased considerably over the first 3-h storage; values dropped by 55% and 34%, respectively. Conversely, as the drain on high energy phosphate pools progressed, there was an increase in low energy adenylate, AMP. Between 10 and 24 h of storage, increases in AMP accounted for approximately 25-30% of total ATP + ADP decrease. The remainder of the drop in adenylates was accounted for by considerable decreases in total adenylate (TA) contents; by 24 h TA contents had decreased by 2.0 micromol/g. Livers from hibernating squirrels exhibited similar patterns of adenylate change and were not significantly higher than their euthermic counterparts. With respect to regulatory control of glycolysis, livers from euthermic squirrels exhibited no regulatory control at phosphofructokinase (PFK) or pyruvate kinase (PK). Livers from hibernating animals, however, showed an activation at PFK by 10 h of cold storage; levels of hexose phosphates, glucose-6-phosphate + fructose 6-phosphate (G6P + F6P), dropped and fructose 1, 6-biphosphate (F1,6P2), increased. Changes in metabolite levels (phosphoenolpyruvate and pyruvate) associated with another key suspect regulatory enzyme, PK, indicated no role in regulatory control of glycolysis during the 24-h period. The apparent increase in PFK responsiveness to declining energy stores may be a futile activation since there was no accompanying increase in anaerobic end product, lactate, and no maintenance of energetics.

Adenine Nucleotides↗

Effects of high fat diets on hibernation and adipose tissue in Turkish hamsters.

The effects of dietary fat saturation and fat content on hibernation and several properties of white and brown adipose tissue (WAT and BAT, respectively) were investigated in Turkish hamsters (Mesocricetus brandti). Male hamsters were housed in a long photoperiod (LD 16:8) at 23 degrees C and fed one of three diets: (1) chow (6.5% fat per weight), (2) chow + 13.5% vegetable oil (OIL, 20% fat per weight [largely unsaturated fat]) and (3) chow + 13.5% vegetable shortening [(SHORTENING, 20% fat per weight (largely saturated fat)]. Five weeks later body weights had stabilized and the animals were transferred to a short photoperiod (LD 8:16) at 3 degrees C. At the peak of the hibernation season (17 weeks) the animals were sacrificed within 24 h of arousal. Chow-fed hamsters had the greatest percentage of animals hibernating and days found torpid compared with the two fat-fed groups, with no differences found between the latter two groups for these measures. There were no differences between hibernating (HIB) and non-hibernating (NON-HIB) hamsters across or within the diet groups for any of the BAT measures [uncoupling protein content, mitochondrial mass, lipoprotein lipase (LPL) activity, and in vivo lipogenesis], nor were there significant effects of the diet on these measures. CHOW- and OIL-fed HIB hamsters showed decreases in body weight. All HIB groups had decreases in each carcass component, several fat pad weights, testes weight, and food intake. No consistent differences in WAT LPL activity or in vivo lipogenesis were found between HIB and NON-HIB hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Effects of cold exposure and hibernation on renal Na,K-ATPase of the jerboa Jaculus orientalis.

Changes in activity and abundance of renal Na,K-ATPase were evaluated during cold exposure and hibernation of the jerboa Jaculus orientalis by measuring the hydrolytic activity, the number of units and the transport activity of Na,K-ATPase in isolated nephron segments. As compared to controls, jerboas exposed to cold (6 degrees C) for 4-5 weeks displayed mild diuresis, decreased urinary osmolality and increased kaliuresis. In cold-exposed jerboas, Na,K-ATPase hydrolytic activity was reduced in the medullary thick ascending limb and enhanced in the cortical and outer medullary collecting duct, whereas it was not altered in other nephron segments. The number of Na,K-ATPase units and the activity of Na,K-pump, determined by [3H]-ouabain binding and by ouabain-sensitive rubidium uptake respectively, changed in parallel with the hydrolytic activity in the medullary thick ascending limb and cortical collecting duct. The maximal rate of activity (Vmax) of Na,K-ATPase was not modified further during hibernation. Thus, cold exposure, but not the onset of hibernation, induces segment-specific changes in the abundance and activity of Na,K-ATPase units which are likely to be related to the entry into hibernation, but not to the maintenance of some renal functions during deep hibernation.

Animals↗

Blood gas analyses of hibernating hamsters and dormice.

Blood gases were measured in hibernating and hypothermic animals as a biological model of clinical hypothermia. Blood gas analyses from hamsters and dormice were carried out with the aid of permanent arterial catheters during normothermia and hibernation. In golden hamster pH increased from 7.30 to 7.46 during hibernation and PaCO2 decreased from 59.7 to 40.5 mm Hg. In dormice pH increased from 7.24 to 7.44 and PaCO2 decreases from 38.5 to 27.4 mm Hg. The actual bicarbonate concentration increased from 29 to 52 mMol in golden hamsters and from 16 to 34 mMol in dormice during hibernation. In experiments with induced hypothermia in golden hamsters under ketamine-anaesthesia there was no correlation between temperature and PaCO2. Despite the slight decrease in PaCO2 during hibernation we conclude that PaCO2 rather than total carbon dioxide content is held constant when temperature is changed. During clinical hypothermia it will probably be safe to keep PaCO2 constant.

Acid-Base Equilibrium↗

Adaptation of intestinal enzymes to seasonal and dietary changes in a hibernator: the European hamster (Cricetus cricetus).

Effects of diet, hibernation and seasonal variations on hydrolase activities were determined in mucosa and purified brush border membranes of the small intestine of European hamsters. Wild hamsters captured in April and fed for several weeks with an equilibrated laboratory chow (20% protein, 50% carbohydrates) exhibited a rise in disaccharidase activities (sucrase, isomaltase, lactase) but no changes in aminopeptidase N activity. During deep hibernation, in contrast to sucrase and isomaltase activities which showed only minor changes, lactase activity was significantly enhanced along the jejunoileum, and aminopeptidase N activity was maximum in the ileum. After a short period (48 h) of wakefulness and feeding following 10 days of starvation during the hibernation period, the activities of the disaccharidases and of aminopeptidase N returned to values measured in active animals. In contrast to the nutritional state, which has an important impact on the activities of intestinal enzymes, season has little effect on the intestine of the active animal under a controlled environment. The pattern of enzyme activities which occurs along the small intestine in the hibernating animal may be a prerequisite for optimum digestion during the short phases of waking during the hibernation period of the European hamster.

Adaptation, Physiological↗

Comparison of hibernation, estivation and daily torpor in the edible dormouse, Glis glis.

Three major forms of dormancy in mammals have been classified: hibernation in endotherms is characterised by reduced metabolic rate (MR) and body temperature (Tb) near ambient temperature (Ta) over prolonged times in the winter. Estivation is a similar form of dormancy in a dry and hot environment during summertime. Daily torpor is defined as reduced MR and Tb lower than 32 degrees C, limited to a duration of less than 24 h. The edible dormouse (Glis glis) is capable for all three distinct forms of dormancy. During periods of food restriction and/or low Ta, daily torpor is displayed throughout the year, alternating with hibernation and estivation in winter and summer respectively. We recorded Tb, O2-consumption and CO2-production in unrestrained dormice at different Ta's for periods of up to several months. Cooling rate and rate of metabolic depression during entrance into the torpid state was identical in all three forms of dormancy. The same was true for thermal conductance, maximum heat production, duration of arousal and cost of an arousal. The only difference between hibernation and daily torpor was found in the bout duration. A daily torpor bout lasted 3-21 h, a hibernation bout 39-768 h. As a consequence of prolonged duration, MR, Tb and also the Tb - Ta gradient decreased to lower values during hibernation bouts when compared to daily torpor bouts. Our findings suggest that all three forms of dormancy are based on the same physiological mechanism of thermal and metabolic regulation.

Animals↗

The role of dietary fatty acids in the evolution of spontaneous and facultative hibernation patterns in prairie dogs.

The white-tailed prairie dog is a spontaneous hibernator which commences deep torpor bouts during early fall while the black-tailed prairie dog is a facultative hibernator that will only enter shallow torpor when stressed by cold and food deprivation. Plant oils rich in polyunsaturated fatty acids (PUFAs) enhance the duration and depth of mammalian torpor. Thus, we tested the hypothesis that black-tailed prairie dogs sampled in the field have less PUFAs in their diets and that the enhancement of torpor bouts by this species on a diet higher in PUFA is less profound than that by white-tailed prairie dogs. Individuals of both species fed a high PUFA diet: (1) entered torpor earlier, (2) had lower torpor body temperatures and (3) had longer bouts of torpor, compared to those on a low PUFA diet. However, the magnitude of this change was similar for both species. Additionally, the PUFA compositions of white adipose tissue (WAT) samples taken from individuals in the field were identical, indicating that diet PUFA contents for these two species were also equivalent. Therefore, while high PUFA diets can enhance hibernation by these species, it does not appear to explain the differences between spontaneous and facultative strategies. The rate of lipid peroxidation during torpor, however, was significantly higher in the WAT from white-tailed prairie dogs. Ancestral prairie dog species are spontaneous hibernators. Natural selection may have favored shallow, facultative hibernation with lower lipid peroxidation rates in the black-tailed prairie dogs as they radiated from the Rocky Mountains into the Great Plains.

Adipose Tissue↗

Rhythmicity of torpor in a marsupial hibernator, the mountain pygmy-possum (Burramys parvus), under natural and laboratory conditions.

Circadian rhythms have been observed in most mammals, but their importance and function remain controversial with respect to daily cycles during hibernation. We investigated the timing of arousals from and entries into hibernation for both free-living and captive mountain pygmy-possums (Burramys parvus). Under both natural and laboratory conditions most arousals and entries were entrained with the light-dark cycle. Entries occurred mainly during the night and arousals preferably around dusk, which coincides with the onset of the normal activity phase for the nocturnal pygmy-possums. This entrainment prevailed throughout the hibernation season although only the laboratory animals were constantly subjected to photoperiodic stimuli, whereas under natural conditions hibernacula are shielded from photic cues and diurnal temperature fluctuations. Nevertheless, possums left their hibernacula frequently throughout winter and were occasionally trapped close to the snow surface suggesting that during the periods of post-arousal normothermia they can be exposed to environmental stimuli. It thus appears that the synchronisation with the photocycle was governed by a temperature-compensated circadian clock which was reset periodically during short activity periods. For the mountain pygmy-possum, entrainment with the photocycle probably has two functions: 1. Entrainment ensures that foraging bouts during the hibernation season remain synchronised with the dark phase. 2. Information about the prevailing climatic conditions sampled during short activity periods enables them to time final spring emergence from hibernation when snow melt begins and ensures that the breeding season can commence as early as possible.

Animals↗