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PubMed1994

Persistence of circadian rhythmicity in hibernating ground squirrels.

The body temperatures (Tb) of golden-mantled ground squirrels maintained under constant dim light (< 20 1x red light) at an ambient temperature of 10 degrees C were monitored via telemetry throughout the hibernation season. During euthermia, when Tb ranged from 34 to 39 degrees C, these animals exhibited robust circadian Tb rhythms. During bouts of hibernation, when Tb rhythms persisted, although the amplitudes of the rhythms were considerably dampened compared with euthermia. The periods of the intrabout Tb rhythms were within the ranges observed during euthermia and were stable within an individual bout but varied between hibernation bouts. Arousals from hibernation occurred at a fixed phase angle of the Tb cycle. Once the period of an intrabout Tb rhythm was determined, it was possible to predict the timing of arousal from the hibernation bout to within 1 h of any 24-h period. This study confirms previous speculation about the persistence of circadian rhythms in golden-mantled ground squirrels during deep hibernation and demonstrates that the circadian system is involved in the timing of periodic arousals from hibernation.

Animals↗
PubMed1995

alpha 2-Macroglobulin gene expression during hibernation in ground squirrels is independent of acute phase response.

alpha 2-Macroglobulin, a major acute phase reactant in many species, increases in the Richardson's ground squirrel (Spermophilus richarsonii) during hibernation at the level of both mRNA and protein. To determine if the pattern of liver gene expression known as the acute phase response is elicited as a normal part of the physiological adaptation of hibernation, acute phase reactants were identified in the Richardson's ground squirrel and were then assayed for changes in mRNA expression in the livers of active and hibernating ground squirrels. Our data demonstrate that alpha 1-antitrypsin, alpha 2-macroglobulin, ceruloplasmin, C-reactive protein, and serum amyloid A are acute phase reactants in the Richardson's ground squirrel. Of these, only alpha 2-macroglobulin (alpha 2M) mRNA increases during hibernation, demonstrating that the entire acute phase response is not elicited as a part of the adaptation for hibernation. Alternatively, data from blood clotting assays of serum from active and hibernating animals support a role for the increase in alpha 2M protein during hibernation in decreasing the coagulative properties of the blood.

Actins↗
PubMed2005

Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal.

Survival of near-freezing body temperatures and reduced blood flow during hibernation is likely the result of changes in the expression of specific genes. In this study, we described a comprehensive survey of mRNAs in the heart of the thirteen-lined ground squirrel (Spermophilus tridecemlineatus) before and during hibernation. The heart was chosen for this study because it is a contractile organ that must continue to work despite body temperatures of 5 degrees C and the lack of food for periods of 5-6 mo. We used a digital gene expression assay involving high-throughput sequencing of directional cDNA libraries from hearts of active and hibernating ground squirrels to determine the identity and frequency of 3,532 expressed sequence tags (ESTs). Statistical analysis of the active and hibernating heart expression profile indicated the differential regulation of 48 genes based on a P < or = 0.03 threshold. Several of the differentially expressed genes identified in this screen encode proteins that likely account for uninterrupted cardiac function during hibernation, including those involved in metabolism, contractility, Ca2+ handling, and low-temperature catalysis. A sampling of genes showing higher expression during hibernation includes phosphofructokinase, pancreatic triacylglycerol lipase, pyruvate dehydrogenase kinase 4 (PDK4), aldolase A, sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a), titin, and four-and-a-half LIM domains protein 2 (FHL2). Genes showing reduced levels of expression during hibernation include cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), troponin C, phospholamban, Ca2+/calmodulin-dependent protein kinase II (CaMKII), calmodulin, and four subunits of cytochrome c oxidase.

Adaptation, Physiological↗
PubMed2006

Detection of differential gene expression in brown adipose tissue of hibernating arctic ground squirrels with mouse microarrays.

Hibernation is an energy-saving strategy adopted by a wide range of mammals to survive highly seasonal or unpredictable environments. Arctic ground squirrels living in Alaska provide an extreme example, with 6- to 9-mo-long hibernation seasons when body temperature alternates between levels near 0 degrees C during torpor and 37 degrees C during arousal episodes. Heat production during hibernation is provided, in part, by nonshivering thermogenesis that occurs in large deposits of brown adipose tissue (BAT). BAT is active at tissue temperatures from 0 to 37 degrees C during rewarming and continuously at near 0 degrees C during torpor in subfreezing conditions. Despite its crucial role in hibernation, the global gene expression patterns in BAT during hibernation compared with the nonhibernation season remain largely unknown. We report a large-scale study of differential gene expression in BAT between winter hibernating and summer active arctic ground squirrels using mouse microarrays. Selected differentially expressed genes identified on the arrays were validated by quantitative real-time PCR using ground squirrel specific primers. Our results show that the mRNA levels of the genes involved in nearly every step of the biochemical pathway leading to nonshivering thermogenesis are significantly increased in BAT during hibernation, whereas those of genes involved in protein biosynthesis are significantly decreased compared with summer active animals in August. Surprisingly, the differentially expressed genes also include adipocyte differentiation-related protein or adipophilin (Adfp), gap junction protein 1 (Gja1), and secreted protein acidic and cysteine-rich (Sparc), which may play a role in enhancing thermogenesis at low tissue temperatures in BAT.

Adipose Tissue, Brown↗
PubMed2004

Levels of gap junction proteins in coronary arterioles and aorta of hamsters exposed to the cold and during hibernation and arousal.

There are marked changes in vascular dynamics during prolonged periods in the cold, entrance into hibernation, and arousal to euthermy. Cell-to-cell communication through gap junction channels plays a pivotal role in the control of vasomotor function. Multiple gap junction proteins are expressed in blood vessels, including connexins 37 (Cx37), 40 (Cx40), 43 (Cx43), and 45 (Cx45). Using immunolabeling techniques combined with confocal microscopy, we quantitated the levels of these connexins in coronary arterioles and the thoracic aorta of the golden hamster in four physiological conditions: normal control animals at euthermy; cold-exposed animals (before entrance into hibernation); during hibernation; and after 2-hr arousal from hibernation. In all groups, Cx37 was localized between endothelial cells of the aorta and Cx40 was observed between endothelial cells of coronary arterioles and the aorta. Cx43 was confined to smooth muscle cells of the aorta. Labeling for Cx45 was detected in the endothelium of the ascending aorta. The expression of Cx37 was significantly reduced in cold-exposed, hibernating, and aroused animals. Immunolabeling for Cx40 was increased in the coronary arteriolar endothelium of the cold-exposed group compared with normal controls, hibernating, and aroused animals, perhaps to facilitate intercellular communication during the prolonged circulatory changes to vascular dynamics required to maintain core temperature during cold adaptation. Cx40 expression was unchanged in the aorta. Cx43 immunoexpression in the aorta remained constant under all conditions examined. These changes in connexin expression did not occur during the rapid circulatory changes associated with arousal from hibernation.

Animals↗
PubMed2001

Hibernation effects on memory in European ground squirrels (Spermophilus citellus).

Effects of hibernation on memory were tested in European ground squirrels (Spermophilus citellus). The animals were trained in summer to successfully accomplish two tasks: a spatial memory task in a maze and an operant task on a feeding machine. One group hibernated normally, and the other was prevented from hibernation by maintaining ambient temperature at 22 degrees C. In spring, the same tasks were repeated for both groups and their individual performances compared to the initial training phase. The experimental groups differed significantly in both tasks. The nonhibernating animals had higher levels of retention and needed significantly fewer trials to relearn the tasks than the group that had hibernated. In addition to testing the retention of conditioned tasks, social memory was also studied. The ground squirrels were given a social recognition test in spring with one familiar and one unfamiliar conspecific. In contrast to the conditioned tasks, social memory did not seem to be affected by hibernation. The results indicate negative effects of hibernation on the retention of conditioned tasks, which could produce important constraints on animals. A potential explanation for this memory loss might be changes in neuronal activity, which occur during hibernation.

Animals↗
PubMed2002

Differential expression of mitochondria-encoded genes in a hibernating mammal.

A cDNA library constructed from kidney of the thirteen-lined squirrel, Spermophilus tridecemlineatus, was differentially screened for genes that were upregulated during hibernation. A clone encoding cytochrome c oxidase subunit 1 was found and confirmed to have been upregulated by northern blotting. Differential expression of Cox1 mRNA occurred in multiple organs during hibernation; in hibernating animals transcript levels were twofold higher in kidney and fourfold higher in heart and brown adipose tissue than in euthermic animals, but were unchanged in skeletal muscle. Transcript levels of mitochondrial-encoded ATP synthase 6/8 were similarly upregulated in these tissues whereas transcript levels of the nuclear encoded subunits Cox4 and ATP synthase alpha did not change during hibernation. Immunoblot analysis revealed a 2.4-fold increase in Cox 1 protein and a slight decrease in Cox 4 protein in kidney of hibernating squirrels, compared with euthermic controls. Hibernating mammals may increase the expression of the mitochondrial genome in general, and Cox1 specifically, to prevent or minimize the damage to the electron transport chain caused by the cold and ischemia experienced during a hibernation bout.

Adaptation, Physiological↗
PubMed2002

Adaptive plasticity of skeletal muscle energetics in hibernating frogs: mitochondrial proton leak during metabolic depression.

The common frog (Rana temporaria) spends the coldest months of each year overwintering in ice-covered ponds where temperatures can vary from 0.5 to 4.0 degrees C. Over the course of a winter season, the animals enter progressively into a state of metabolic depression that relies almost exclusively on aerobic production of ATP. However, if aerobic metabolism is threatened, for example by increasingly hypoxic conditions, decreases in the animal's metabolic rate can reach upwards of 75% compared with the 50% decrease seen during normoxia. Under these conditions, the major proportion of the overall reduction in whole-animal metabolic rate can be accounted for by metabolic suppression of the skeletal muscle (which makes up approximately 40% of body mass). Little is known about the properties of mitochondria during prolonged periods of metabolic depression, so we have examined several aspects of mitochondrial metabolism in the skeletal muscle of frogs over periods of hibernation of up to 4 months. Mitochondria isolated from the skeletal muscle of frogs hibernating in hypoxic water show a considerable reorganisation of function compared with those isolated from normoxic submerged animals at the same temperature (3 degrees C). Both the active (state 3) and resting (state 4) respiration rates of mitochondria decrease during hypoxic, but not normoxic, hibernation. In addition, the affinity of mitochondria for oxygen increases during periods of acute hypoxic stress during normoxic hibernation as well as during long-term hibernation in hypoxic water. The decrease in mitochondrial state 4 respiration rates during hypoxic hibernation evidently occurs through a reduction in electron-transport chain activity, not through a lowered proton conductance of the mitochondrial inner membrane. The reduced aerobic capacity of frog skeletal muscle during hypoxic hibernation is accompanied by lowered activities of key enzymes of mitochondrial metabolism caused by changes in the intrinsic properties of the mitochondria. In the absence of oxygen, the mitochondrial F(1)F(o)-ATPase (the ATP synthase) begins to run backwards as it actively pumps protons from the matrix in an attempt to maintain the mitochondrial membrane potential. At this time, the ATP synthase functions as an ATPase to preserve a certain proton-motive force. Frogs limit ATP wastage during anoxia by a profound inhibition of the ATP synthase. Taken together, our studies show that protonmotive force is lowered aerobically by restricting electron supply and during anoxia by restricting mitochondrial ATPase activity.

Animals↗
PubMedDate not supplied

The modulation of the calcium transport by skeletal muscle sarcoplasmic reticulum in the hibernating European hamster.

Calcium transport of skeletal muscle sarcoplasmic reticulum was comparatively studied in hibernating and summer active European hamsters (Cricetus cricetus L.). Crude homogenates from psoas, soleus and mixed skeletal muscles were used. Protein yield was strongly reduced in the muscle homogenates of hibernating hamsters. The calcium concentration in the muscle of hibernating hamsters was increased to a much higher content than in the serum. In the same animals the maximal rate of calcium uptake and the calcium storing capacity of sarcoplasmic reticulum were augmented by 43% and respectively 17%. Kinetic experiments with various concentrations of free calcium revealed in the hibernating animals higher uptake rates and a lower apparent calcium affinity than in the summer active hamsters. Some shift of calcium uptake rate and calcium affinity similar to that of a fast-twitch muscle was also observed in winter active animals kept at 22 degrees C under natural photoperiod. By contrast, the activity of the calcium dependent ATPase was not increased, suggesting a tighter coupling during hibernation between calcium dependent ATP-hydrolysis and calcium transport. No seasonal difference was observed in the calcium release by KCl-caffeine from calcium loaded vesicles of sarcoplasmic reticulum. Proportion and size of fibre types were studied with cold cross sections from psoas and soleus muscles. An average atrophy of about 25% was found during hibernation in both muscles. Cytochemistry revealed, however, a different reduction of cross area between type-I- and type-II-fibres, which reaches values up to 46% in the type-II-fast-fibres of the slow soleus muscle. Electron microscopy did not show any definite change in the distribution and amount of sarcoplasmic reticulum. The results suggest that during hibernation a modulation in the properties of calcium transport ATPase of sarcoplasmic reticulum occurs to better support the calcium transport function at low temperatures, which in turn warrants the restoration of ion homeostasis in the course of the arousal.

Adenosine Triphosphatases↗
PubMed2006

Winter hibernation and body temperature fluctuation in the Japanese badger, Meles meles anakuma.

This study examined seasonal changes in body weight, hibernation period, and body temperature of the Japanese badger (Meles meles anakuma) from 1997 to 2001. Adult badgers showed seasonal changes in body weight. Between mid-December and February, badger activity almost ceased, as the animals remained in their setts most of the time. Adult male badgers were solitary hibernators; adult females hibernated either alone or with their cubs and/or yearlings. The total hibernation period of Japanese badgers ranged from 42 to 80 days, with a mean length of 60.1 days. Japanese badgers did not always spend the winters in the same sett, although they seldom changed setts during hibernation. I equipped a male cub with an intraperitoneally implanted data logger to record its body temperature between November and April, while the cub hibernated with its mother. Over the winter, the body weight of the cub decreased from 5.3 kg to 3.6 kg, a weight loss of 32.1%, and its body temperature ranged from 32.0 to 39.8 degrees C. The mean monthly body temperature was 35.1 degrees C in December, 34.8 degrees C in January, 35.9 degrees C in February, 37.1 degrees C in March, and 37.4 degrees C in April, so the monthly decrease in body temperature of this cub was not great. The results indicate that during hibernation, when body temperature is low, there is likely considerable economy of energy and a reduced demand for adipose reserves.

Animals↗
PubMed1999

Ultrastructural localization of nitric oxide synthase and endothelin in the renal and mesenteric arteries of the golden hamster: differences during and after arousal from hibernation.

This is a study of the electron-immunocytochemical localization of nitric oxide synthase (type III) and endothelin in renal and mesenteric artery endothelial cells of normal (active) and hibernating hamsters, as well as hamsters exposed to the cold but not hibernating, and hamsters aroused for 2h following hibernation. In the renal artery of hibernating hamsters and cold-exposed hamsters, a subpopulation of nitric oxide synthase-positive endothelial cells displayed immunoprecipitate predominantly in the vicinity of the Golgi complex indicating intracellular translocation from the cytoplasm to the Golgi complex. In hibernating animals, the percentages of both nitric oxide synthase-positive and endothelin-positive endothelial cells were notably lower than those observed either in active, cold-exposed or aroused animals. These changes may reflect a reduced endothelial contribution to the maintenance of vascular tone in these vessels during hibernation and an upregulation of expression of nitric oxide synthase and endothelin in the endothelium early on during arousal from hibernation.

Animals↗
PubMed2003

Different thermostability of skeletal muscle glyceraldehyde-3-phosphate dehydrogenase from hibernating and euthermic jerboa (Jaculus orientalis).

In previous study, we demonstrated that the specific activity of D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) in skeletal muscle of induced hibernating jerboa (hibernating GAPDH) was 3 4 folds lower than that of the one in the skeletal muscle of the euthermic jerboa (euthermic GAPDH). A significant decrease in both GAPDH protein and GapC mRNA levels occurs when hibernating, but the purified hibernating GAPDH is less active than the euthermic GAPDH. To investigate the physico-chemical basis of this lower activity, the behaviour during thermal inactivation of skeletal muscle GAPDH from hibernating and euthermic tissues was examined by a variety of spectroscopic techniques, including fluorescence emission, circular dichroism and ultraviolet absorption. A clear resistance to thermal denaturation was observed in the hibernating GAPDH compared with the euthermic GAPDH. The different temperature of denaturation found in these proteins by both fluorimetry and circular dichroism indicates that there might exist conformational changes of GAPDH upon hibernation that could affect the stability of this enzyme.

Animals↗
PubMed1991

The hibernator heart--nature's model of resistance to ventricular fibrillation.

During hibernation the animals decrease their body temperature down to a few degrees above 0 degree C. This means that when entering into and arousing from hibernation their body temperature passes the critical level of 20 degrees C, a temperature region where nonhibernating mammals develop circulatory arrest, usually ventricular fibrillation (VF). We found in other experiments that the hibernator heart is resistant to VF, not only induced by hypothermia, but also when induced by local application of aconitine on the epicardium, addition of 0.55 molar CaCl2 to isolated hearts perfused with a potassium free Tyrode solution, addition of procaine to isolated hearts perfused with Tyrode solution after previous administration of adrenaline, ligation of the proximal part of the left anterior descending coronary artery, and electrical stimulation in the vulnerable phase of the heart cycle. Several mechanisms are at work to explain this resistance to VF of the hibernator heart when compared to the nonhibernator heart. The factors of greatest importance seem to be the different adrenergic innervation pattern, different physico-chemical properties with a lower melting point of the lipids in the hibernator, different enzyme temperature activity curves in the hibernator and a different handling of intracellular calcium resulting in a protection against calcium overload in the hibernator heart, when compared with the nonhibernator heart.

Animals↗
PubMed1990

[The effect of medium tonicity on the rate of respiration and oxidative phosphorylation in liver mitochondria of active and hibernating ground squirrels].

The rate of respiration and ATP synthesis in liver mitochondria (M) isolated from hibernating ground squirrels and incubated in the medium with normal tonicity (250 mosm) was shown to be considerably lower than the rate of respiration and ATP synthesis in liver M from active animals. The increase of the medium tonicity to 600 mosm simulated the state of M from hibernating animals, resulting in a decrease of the respiration rate of M from active ground squirrels. On the contrary, the decrease of the tonicity to 60 mosm caused the activation of the respiration and increase of the ATP synthesis in M from hibernating ground squirrels. Bromophenacylbromide (BPhB), an inhibitor of phospholipase A2, prevented the activation of the respiration of M from hibernating animals incubated in the medium with low tonicity. BPhB had practically no effect on the respiration of M from both hibernating and active ground squirrels as well as on the swelling of M in hypotonic medium. It was concluded that the activation of the respiration and increase of the ATP synthesis rate in M from hibernating ground squirrels incubated in the medium with low tonicity is related to the activation of phospholipase A2. It was assumed that decrease of phospholipase A2 activity and change in the lipid composition of mitochondrial membrane may be one of the reasons for inhibition of the respiration rate in M from hibernating ground squirrels.

Adenosine Triphosphate↗
PubMed1997

The kinetic characteristics of L-type calcium channels in cardiac cells of hibernators. 2. Analysis of the kinetic model.

The present paper describes the experimental and theoretical investigations of the kinetic characteristics of the L-type Ca2+ channels in ground squirrels Citellus undulatus in two different physiological states (hibernation and spontaneous arousal). The perforated patch-clamp method was used in the experiments. We have shown in the previous study [1] that Ca2+ currents in hibernating and active animals may be described by the d2f1(2)f2 model. Based on that model, in this paper we studied in detail the main steps of the conductance regulation of Ca2+ channels: activation (d), slow (f1-type) and fast (f2-type) inactivations of the channel. Activation is related to the movement of the gating charge. Slow inactivation is associated with the movement of the gating charge and is current-dependent. Fast inactivation is a more complex process and cannot be represented as a single-stage conformational transition induced by the gating charge movement. It is regulated by cAMP phosphorylation. The differences in the Ca2+ current kinetics are observed virtually for all the components. In hibernating animals, the most pronounced shift (15-20 mV) towards depolarization is experienced by the normalized conductances of both inactivation components, whereas the conductance of the activation component is shifted to a lesser extent. The characteristic times of Ca2+ currents of hibernating ground squirrels are 1.5-2 times greater than those of aroused animals. The current activation gating charge of Ca2+ channels in ground squirrel cardiocytes was found to change. The gating charge was about 2 in hibernating animals and 1.5 in active squirrels. The effect of isoproterenol-induced cAMP-dependent phosphorylation on Ca2+ currents in cardiocytes from hibernating ground squirrels was studied. Isoproterenol restored the kinetic parameters of Ca2+ currents to the values close to the parameters of active animals. However, we failed to explain the suppression of the Ca2+ current in hibernating animals in terms of cAMP-dependent regulation only.

Animals↗
PubMed1989

The serotonin-immunoreactive system of the suprachiasmatic nucleus in the hibernating ground squirrel, Spermophilus richardsonii.

In the suprachiasmatic nucleus (NSC) of hibernating and non-hibernating ground squirrels, the distribution of serotonin-immunoreactive (5HT-IR) fibers was studied by the use of the peroxidase-antiperoxidase technique. The cytology of perikarya giving rise to these suprachiasmatic 5HT-IR fibers was investigated in the anterior raphe nuclei. Differences in the immunoreactivity of suprachiasmatic fibers between hibernating and non-hibernating ground squirrels were determined by digital image analysis. The cellular activity was determined by digital image analysis. The cellular activity was determined densitometrically after RNA-staining in anterior raphe neurons and suprachiasmatic perikarya. Abundant 5HT-IR fibers were observed in the medial and ventromedial portions of the NSC. Frequently, the fibers were found in close contact with perikarya of suprachiasmatic neurons. The central portion of the nucleus and the surrounding hypothalamic areas contained only a few scattered 5HT-IR fibers. Inside the raphe nuclei, 5HT-IR fibers and perikarya formed a dense network. In hibernating ground squirrels, the immunoreactivity to serotonin was approximately 45% higher than in non-hibernating controls. This difference is in accordance with signs of higher neuronal activity (40% higher RNA-content, 20% larger cell nuclei) in 5HT-IR perikarya of the raphe nucleus and the persisting activity of the NSC during hibernation; the activity of other brain regions dropped conspicuously in torpid animals.

Animals↗
PubMed2003

Comparison of sestamibi, thallium, echocardiography and PET for the detection of hibernating myocardium.

The detection of hibernating myocardium is important because revascularisation results in improved function and prognosis in patients with hibernation but not in those with non-viable myocardium. The primary aim of this study was to compare the diagnostic accuracy of four techniques with respect to hibernation in the same study population with 6-12 months of follow-up. Twenty-five males underwent rest-stress sestamibi and delayed (>18 h) thallium scintigraphy, high-dose dobutamine stress echocardiography and nitrogen-13 ammonia/fluorine-18 fluorodeoxyglucose (NH(3)/FDG) positron emission tomography (PET). The pre-operative ejection fraction was 36.2% (+/-7.3%). Follow-up was 8.1 (+/-2.8) months. Using postoperative improvement in wall motion on echocardiography as the gold standard, 6/34 dysfunctional vascular territories were hibernating. The mean uptake of all tracers was significantly higher in hibernating than in non-viable territories ( P<0.05). Normal perfusion or mismatch on PET (FDG>NH(3) uptake) and the pattern of response to dobutamine on echocardiography were also predictive of recovery ( P<0.001 and P=0.02 respectively). Univariate logistic regression identified sestamibi, ammonia and FDG as independent predictors of hibernation. FDG-PET was, however, the only independent predictor using multivariate analysis. The nuclear techniques had high negative predictive values (NPV) of >or=95% but lower positive predictive values (PPV) of 45%-75% as compared with echocardiography, which had an NPV of 87% and a PPV of 100%. PET was the most powerful predictor of hibernation although the combination of a technique with a high PPV (echocardiography) and a high NPV (PET or sestamibi) may represent the optimal clinical choice.

Adult↗
PubMed2006

Adaptation of nonrevascularized human hibernating and chronically stunned myocardium to long-term chronic myocardial ischemia.

It is unknown whether human chronically ischemic dysfunctional myocardium degenerates over time or adapts to chronic ischemia. We studied whether perfusion, metabolism, and contractile function and reserve can be preserved in nonrevascularized human chronically stunned and hibernating myocardium. We studied 16 event-free, medically treated patients with ejection fractions of 31 +/- 2% and chronically stunned or hibernating myocardium in 56 +/- 5% of the left ventricle on technetium-99m sestamibi single-photon emission computed tomography/fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography. Patients underwent repeat single-photon emission computed tomography, positron emission tomography, and tissue Doppler echocardiography at rest and during stress at follow-up after 25 +/- 4 months, and we investigated whether measurements of myocardial viability remained stable over time. Patients were stable with respect to New York Heart Association class and global left ventricular function (30 +/- 2%, p = 0.81). Wall motion score was unaltered in hibernating myocardium and chronically stunned regions, and a contractile reserve by tissue Doppler stress echocardiography was preserved. Overall, 74% of hibernating myocardium and chronically stunned regions retained their initial perfusion/metabolism pattern at follow-up. In hibernating myocardium, initial and follow-up sestamibi uptakes (53 +/- 1% and 53 +/- 2%, p = 0.85) and FDG uptakes (76 +/- 1% and 74 +/- 1%, p = 0.21) did not differ. In chronically stunned regions, sestamibi uptake displayed a minor decrease at follow-up (70 +/- 1% vs 67 +/- 1%, p <0.01) and FDG uptake remained constant (68 +/- 2% and 67 +/- 1%, p = 0.21). In conclusion, myocardial perfusion, FDG uptake, and contractile function in nonrevascularized chronically stunned and hibernating myocardium adapt to chronic ischemia in patients who are free of events. In chronically stunned regions, adaptation may be less complete than in hibernating myocardium.

Adaptation, Physiological↗