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PubMed2005

[Hibernation and stunning as manifestations of ischemic dysfunction of the myocardium].

Hibernation and stunning are phenomena which constitute a basis of dysfunction of the myocardium appearing as a consequence of chronic ischemic heart disease and of myocardial revascularization. Myocardial stunning is an acute derangement of contractility of ischemic myocardium at the moment of restoration of coronary blood flow by various interventions (bypass grafting, angioplasty, thrombolysis). Myocardial hibernation implies presence of chronically developing foci of reduced contractility located in the area of myocardium supplied by obstructed artery. There is a following difference between these phenomena: stunning is a complex of structural and metabolic disorders during the state of "ischemia-reperfusion" while hibernation is a process of adaptation of the myocardium to chronic ischemia consisting in switch of metabolism to alternative type of energy production (anaerobic glycolysis). Exploration of pathophysiology and morphology of hibernating and stunned myocardium is necessary for elaboration of methods of protection against ischemic injury.

Diagnosis, Differential↗
PubMed1995

[Detection of hibernating myocardium in patients with myocardial infarction by low-dose dobutamine echocardiography: comparison with thallium-201 scintigraphy with reinjection].

The identification of hibernating myocardium is important for selecting patients who will benefit from coronary revascularization. The relationship between echocardiographic and radioisotopic markers of hibernating myocardium and postrevascularization recovery of myocardial function was investigated in 21 patients who underwent successful revascularization. Each patient underwent low-dose dobutamine stress echocardiography and thallium-201 (201Tl) scintigraphy with reinjection before revascularization. The presence of contractile reserve in dobutamine stress echocardiography and Tl uptake in 201Tl scintigraphy with reinjection were defined as markers of hibernating myocardium. Follow-up echocardiograms were evaluated for improved regional wall motion in all patients at a mean of 8.6 months after revascularization. Sensitivity, specificity, and positive and negative predictive values of low-dose dobutamine stress echocardiography for indicating recovery of function after revascularization were 75.0%, 77.8%, 81.8%, and 70.0%, respectively. Sensitivity, specificity, and positive and negative predictive values of 201Tl scintigraphy with reinjection for indicating recovery of function after revascularization were 91.7%, 55.6%, 73.3%, and 83.3%, respectively. There were no statistical differences between low-dose dobutamine echocardiography and 201Tl scintigraphy in predicting postrevascularization recovery of function patients with hibernating myocardium.

Aged↗
PubMed1993

[The "stunned" and "hibernating myocardium"--diagnosis and clinical implications].

Myocardial stunning and myocardial hibernation gain increasing importance for the therapy of myocardial ischemia. It has been demonstrated that myocardial stunning may be reversible after successful reperfusion, although this may need weeks or even months. Similarly, noncontracting myocardial areas may regain contractile properties after successful dilatation of high grade stenoses or after bypass operation (myocardial hibernation). The diagnosis of myocardial stunning or myocardial hibernation usually is made by nuclear medicine (201Tl or 99Tc-MIBI). 201Tl-Imaging after 24 hours or after reinjection seems to be the best method to prove myocardial hibernation. Dobutamine stress echocardiography may gain importance in the future.

Angioplasty, Balloon, Coronary↗
PubMed1997

Left ventricular remodeling in myocardial hibernation.

BACKGROUND: Left ventricular (LV) remodeling as a consequence of extensive myocardial infarction has been well established in animal and human studies. This study was designed to determine whether regional LV dysfunction with myocardial hibernation without transmural or extensive infarction could initiate the remodeling process. METHODS AND RESULTS: A severe left anterior descending coronary artery stenosis was created to reduce resting flow by approximately 40% (from 0.99+/-0.10 to 0.56+/-0.11 mL x min(-1) x g[-1]) and was maintained for 7 days in 13 pigs. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening, from 37+/-3% at baseline to 9+/-7%, regional lactate production and a decrease in regional coronary venous pH. All pigs had significant regional LV dysfunction and reduced LV ejection fraction (41+/-11%). The LV end-diastolic volume increased from 59+/-9 mL at baseline to 74+/-13 mL immediately after placement of the stenosis and to 78+/-17 mL 7 days later with hibernating myocardium. The LV mass did not change immediately (60+/-8 g baseline versus 59+/-11 g immediately after creation of the stenosis) but increased modestly yet significantly to 67+/-15 g after 7 days of myocardial hibernation subtending the severe LAD stenosis. The reductions of coronary flow and wall thickening were unchanged at 7 days, whereas myocardial lactate production recovered. By 4 weeks after restoration of LAD flow, regional function had recovered in all 7 pigs with follow-up. Of the 13 pigs, 6 were free from any evidence of myocardial infarction, and 4 had patchy necrosis involving less than 6% of the area at risk. CONCLUSIONS: LV remodeling, which is commonly associated with extensive myocardial infarction, can be initiated by regional dysfunctional hibernating myocardium resulting from a severe coronary stenosis. Myocardial necrosis is not a prerequisite for LV remodeling in response to regional dysfunction.

Animals↗
PubMed1998

[Hibernating myocardium. An incomplete adaptation to ischemia].

BACKGROUND: We tested the hypothesis that hibernating myocardium represents an incomplete adaptation to a reduced myocardial oxygen supply. METHODS AND RESULTS: In 38 patients, areas of hibernating myocardium were identified by angiography, multigated radionuclide ventriculography, thallium scintigraphy with reinjection, and low-dose dobutamine echocardiography. Biopsies removed at cardiac surgery showed structural degeneration characterized by a reduced protein and mRNA expression and disorganization of the contractile and cytoskeletal proteins myosin, actin, desmin, titin, alpha-actinin, and vinculin by electron microscopy, immunohistochemistry, and in situ hybridization. Additionally, an increased amount of extracellular matrix proteins resulting in a significant degree of reparative fibrosis was present. Dedifferentiation, i.e., expression of fetal proteins, was absent. Apoptosis indicating suicidal cell death was found by the terminal deoxynucleotidyl transferase end-labeling method and electron microscopy. Radionuclide ventriculography showed improvement of regional function at 3 months postoperatively compared with preoperative values (mean values, 23.5% and 48%, respectively), and the echocardiographic wall-motion score index decreased from 3.4 to 1.8. The degree of severity of the morphological changes (three stages) correlated well with the extent of postoperative functional recovery: more advanced clinical improvement was observed in patients with slight and moderate morphological degeneration (stages 1 and 2), but recovery was only partial in severe degeneration (stage 3). CONCLUSIONS: Cellular degeneration rather than adaptation is present in hibernating myocardium. The consequence is progressive diminution of the chance for complete structural and functional recovery after restoration of blood flow. The practical consequence from this study should be early revascularization in patients showing areas of hibernating myocardium.

Humans↗
PubMed1984

Seasonal variations in pituitary thyrotropes of the hibernating bat Myotis lucifugus lucifugus: an immunohistochemical study.

Pituitary thyrotropes were identified throughout the year in the hibernating bat Myotis lucifugus lucifugus by means of light microscopic immunohistochemistry. These cells occupied a small proportion of the volume of the pars distalis (mean = 1.36% in males; mean = 1.52% in females) and exhibited a limited distribution pattern that was characteristic of all animals examined. Cells that were immunoreactive with an antiserum directed against the beta subunit of thyroid-stimulating hormone were most numerous in the median rostral and ventral regions; they were scarce or absent in the dorsal portion of the gland and in the extreme lateral wings. No significant seasonal variations were observed in this cell population in females. In males, however, immunoreactive thyrotropes occupied a significantly larger proportion of the pars distalis in June (following arousal from hibernation than at other times of year. No evidence of involution was observed in these anterior pituitary cells in either males or females during hibernation.

Animals↗
PubMed1981

Histopathological reactions an axonal regeneration in the transected spinal cord of Hibernating squirrels.

The failure of axonal regeneration in the transected spinal cord of mammals has been attributed to many factors, including an intrinsic lack of regenerative capacity of mature CNS neurons, mechanical obstruction of axonal elongation by glial-connective tissue scars, necrosis of spinal tissue resulting in cavitation, lack of trophic influences sufficient to sustain outgrowth, and contact inhibition resulting from the formation of aberrant synapses. Assessment of te relative importance of each of these factors requires animal models in which one or more of these pathological processes can be eliminated. We therefore examined the effects of spinal transection in the hibernating animal because, during hibernation, collagen formation is depressed while nerve regeneration and slow axonal transport are maintained. Midthoracic spinal transections were performed in hibernating ground squirrels and the spinal cords were examined histologically 1-6 months later. The lesion site was composed primarily of a loose accumulation of macrophages and showed minimal glial and collagenous scarring, or cavitation. There was extensive regeneration of intrinsic spinal cord and dorsal root fibers. These axons grew to the margin of the lesion where they turned abruptly and continued growing along the interface between the lesion and the spinal cord. We conclude (1) that mammalian spinal-cord neurons have considerable regenerative potential; (2) that such mechanical impediments as collagenous and glial scarring, cyst formation, and cavitation cannot provide the sole explanation of why regeneration in the mammalian CNS is abortive; and (3) that specific physical and chemical properties of the cells in the environment of the growth cone regulate the extent and orientation of regenerative axonal outgrowth.

Animals↗
PubMed1991

Internalization of erythrocytes into liver parenchymal cells in naturally hibernating frogs (Rana esculenta L.).

Mature and intact red blood cells were found in hepatocytes of frogs during natural underground hibernation. No signs of erythrophagocytosis, e.g., separating membranes between erythrocyte and hepatocyte cytoplasm, and lysosomes, were observed. Red blood cells probably penetrated into hepatocytes by ameboid-like mechanisms, which can be deduced by cytoplasmic protrusions and invaginations. Most of the hepatocytes had large amounts of stored glycogen and few organelles, often segregated in condensed areas. The narrowed bile canalicular lumens without lysosomes and exocytotic vacuoles around them and the reduction of the Disse spaces indicate a low metabolic activity of liver during natural hibernation. The dramatic accumulation of red cells in the hepatocytes of hibernating frogs could share similarities with the phenomenon of internalization of leucocytes into epithelial cells of some vertebrate's tissues via emperipolesis, the mechanisms of which are not well understood.

Animals↗
PubMed2006

Differential expression of selected mitochondrial genes in hibernating little brown bats, Myotis lucifugus.

High rates of non-shivering thermogenesis by brown adipose tissue accompanied by additional shivering thermogenesis in skeletal muscle provide the powerful reheating of body organs that allows hibernating mammals to return from their state of cold torpor back to euthermic function. Previous studies have suggested that changes to brown adipose mitochondria occur during hibernation and are partially responsible for its capacity for non-shivering thermogenesis. The current study shows that selected mitochondrial enzyme activities are elevated and selected genes and proteins are induced during torpor in brown adipose tissue of the little brown bat, Myotis lucifugus. Cytochrome oxidase activity in brown adipose tissue was more than 3-fold higher during torpor than in euthermic animals. Transcript levels of mitochondria-encoded genes, coxII and nad4, were also 3-4-fold higher during torpor, as evidenced by northern blotting. By contrast, transcripts of these genes were unchanged in skeletal muscle during torpor. Protein levels of carnitine palmitoyl transferase-1beta, an enzyme embedded in the outer membrane of the mitochondria that is the rate-limiting step enzyme in beta-oxidation, were also elevated by 2-fold during torpor in brown adipose but were unchanged in skeletal muscle. Cloning and sequencing of a 624 bp segment of cpt-1beta revealed a number of amino acid substitutions in the bat protein as compared to CPT-1beta from other mammals; these may be beneficial for enzyme function at low body temperatures during torpor. This study provides further evidence for a key role of mitochondria in hibernation.

Adipose Tissue, Brown↗
PubMed2005

Hibernation induction trigger reduces hypoxic damage of swine skeletal muscle.

A link between the cardioprotective benefits of pharmacological preconditioning and natural mammalian hibernation is considered to involve the cellular activation of opioid receptors and subsequent opening of K(ATP) channels. In previous studies, we have demonstrated the protective effects of specific delta-opioid agonists against porcine cardiac ischemia/reperfusion injury. We hypothesize here that preincubation with hibernation induction trigger (HIT) should confer a similar protection in skeletal muscles. Therefore, muscle bundles from swine were pretreated with plasma from hibernating woodchucks (HWP) for 30 min, then exposed to hypoxia for 90 min and reoxygenation for 120 min. Stimulated twitch forces were assessed. The functional effects of pretreatment with nonhibernation (summer) woodchuck plasma, a K(ATP) blocker, or opioid antagonist were also studied. During the reoxygenation period, significantly greater force recoveries were observed only for bundles pretreated with HWP; this response was blocked by naloxone (P < 0.05). We conclude that HIT pretreatment could be used to confer protection against hypoxia/reperfusion injury of skeletal muscles of nonhibernators; it could potentially be utilized to prevent injury during surgical procedures requiring ischemia.

Animals↗
PubMed1978

Hibernation as a model for studies on thermogenesis and its control.

Mammalian hibernation is characterized by the alternation of prolonged periods of hypothermia and spontaneous arousals with a temporary return to euthermia. Of special interest to the physiology of effectors of thermogenesis are the following points: a) In the second part of the arousal process, the metabolic rate reaches 6 to 8 times BMR, with a body temperature about 10 degrees C lower. Enzymatic adaptations provide for the maintenance of normal reaction rates and regulatory potentials at low temperatures, but how very high thermogenetic rates can be achieved still remains largely unexplained. b) Entrance into hibernation involves a resetting of the hypothalamic thermostat to a lower level, but this is probably not the only intervening regulation. Evidence is presented in favor of a control of thermogenesis at the effector level, in terms both of baseline levels and of loop gains. One likely control factor is acid-base state, which can be changed rapidly and reversibly by ventilation and is characterized by a strong acidosis in hibernation.

Animals↗
PubMed1977

Ultrastructural changes in the mitochondria of brown adipose cells during the hibernation cycle of Citellus lateralis.

The mitochondrial structure in the brown adipose cells of the golden mantled squirrel, Citellus lateralis, was examined throughout the year in biopsy samples. The mitochondria showed remarkable and apparently reversible changes in size and internal structure related to the physiologic activity of the animal. In the active animal the size of the largest mitochondria was 2.4 micrometer X 1.5 micrometer; during hibernation it increased to 7 micrometer X 2.5 micrometer; and during arousal it reached 11.2 micrometer X 5.3 micrometer. The cristae of the mitochondria in the brown adipose cells of the animals in hibernation phase formed loops, whorls and mesh-like interconnections. During the arousal phase they underwent further configurational changes. The most remarkable structure was associated with mitochondria of most unusual proportions which by dissolution gave rise to a new generation. This was a common finding during arousal but did not occur in any other phase of the hibernation cycle. The new mitochondria were virtually indistinguishable from those of brown adipose cells of any active animal.

Adipose Tissue, Brown↗
PubMed1993

The effect of temperature on the pattern of torpor in a marsupial hibernator.

Physiological variables of torpor are strongly temperature dependent in placental hibernators. This study investigated how changes in air temperature affect the duration of torpor bouts, metabolic rate, body temperature and weight loss of the marsupial hibernator Burramys parvus (50 g) in comparison to a control group held at a constant air temperature of 2 degrees C. The duration of torpor bouts was longest (14.0 +/- 1.0 days) and metabolic rate was lowest (0.033 +/- 0.001 ml O2.g-1 x h-1) at 2 degrees C. At higher air temperatures torpor bouts were significantly shorter and the metabolic rate was higher. When air temperature was reduced to 0 degrees C, torpor bouts also shortened to 6.4 +/- 2.9 days, metabolic rate increased to about eight-fold the values at 2 degrees C, and body temperature was maintained at the regulated minimum of 2.1 +/- 0.2 degrees C. Because air temperature had such a strong effect on hibernation, and in particular energy expenditure, a change in climate would most likely increase winter mortality of this endangered species.

Animals↗
PubMed1995

Novel nuclear ribonucleoprotein structural components in the dormouse adrenal cortex during hibernation.

Adrenocortical cell nuclei of the dormouse Muscardinus avellanarius were investigated by electron microscopic immunocytochemistry in hibernating, arousing and euthermic individuals. While the basic structural constituents of the cell nucleus did not significantly modify in the three groups, novel structural components were found in nuclei of hibernating dormice. Lattice-like bodies (LBs), clustered granules (CGs), fibrogranular material (FGM) and granules associated with bundles of nucleoplasmic fibrils (NF) all contained ribonucleoproteins (RNPs), as shown by labeling with anti-snRNP (small nuclear RNP), anti-m3G-capped RNA and anti-hnRNP (heterogeneous nuclear RNP) antibodies. Moreover, the FGM also showed immunoreactivity for the proliferation associated nuclear antigen (PANA) and the non-snRNP splicing factor SC-35. All these nuclear structural components disappeared early during arousal and were not found in euthermic animals. These novel RNP-containing structures, which have not been observed in other tissues investigated so far in the same animal model, could represent storage and/or processing sites for pre-mRNA during the extreme metabolic condition of hibernation, to be quickly released upon arousal. NFs, which had been sometimes found devoid of associated granules in nuclei of brown adipose tissue from hi-bernating dormice, were present in much higher amounts in adrenocortical cell nuclei; they do not contain RNPs and their role remains to be elucidated. The possible roles of these structures are discussed in the frame of current knowledge of morpho-functional relationships in the cell nucleus.

Adrenal Cortex↗
PubMed1995

Kidney structure and function of obligate and facultative hibernators: the white-tailed prairie dog (Cynomys leucurus) and the black-tailed prairie dog (Cynomys ludovicianus).

The white-tailed prairie dog is an obligate hibernator that enters a heterothermic phase when maintained in the cold with low intensity light and ad libitum food and water. The black-tailed prairie dog (a facultative hibernator) will not hibernate under similar conditions. It has been suggested that the black tailed prairie dog remains active during the winter because it can conserve water more effectively due to a more efficient kidney. The present study revealed no significant differences between the species in renal morphology: relative medullary thickness, nephron heterogeneity, renal vasculature, or fornix dimensions, all of which are structures associated with the urinary concentrating mechanism. In addition, there was no difference in number of nephrons between the two species. The black-tailed prairie dog does produce a more concentrated urine when food and water deprived. However, this difference was not observed when the animals were salt loaded. The water-deprivation and salt-loading experiments suggest that the higher urine osmolality produced by the back-tailed prairie dog during fasting is a result of a higher urea load due to a greater protein catabolism and not because of a differential capacity to concentrate urine.

Adaptation, Physiological↗
PubMed1984

Influence of animal hibernation on the development of mycoses.

The development of adiaspiromycosis and trichophytosis depending upon the state of activity of red-cheeked squirrels is described. The conidia of Chrysosporium (Emmonsia) parvum var. crescens, are not transformed into adiaspores when injected into hibernating animals. During the hibernation period of four months, most of the conidia die. After awakening, the remaining viable conidia are transformed into adiaspores. During hibernation the squirrels, which had been infected with Trichophyton mentagrophytes var. granulosum, developed a symptom-free infection.

Animals↗
PubMed1977

Thermoregulation during entrance into hibernation.

The hypothalamic temperature (Thy) and the rate of oxygen consumption of golden-mantled ground squirrels were continuously measured as they entered hibernation. Thy was manipulated with chronically implanted, water-perfused thermodes. A threshold Thy for eliciting an increase in metabolic heat production was demonstrable at all times during entry. During smooth entries this threshold Thy showed a progressive decline so that it was below actual Thy at all times. These results are interpreted to mean that the normal mammalian central nervous regulator of body temperature is functional throughout the entrance into hibernation, and it can be reset to any level over the 35 degrees C range body temperatures experienced by the hibernator.

Adaptation, Physiological↗