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PubMed2002

The histology of viable and hibernating myocardium in relation to imaging characteristics.

OBJECTIVES: This study characterizes the histology of myocardium predicted to be hibernating using three different imaging techniques to explain the discordance among them. BACKGROUND: Both radionuclide and functional imaging techniques were used to assess myocardial hibernation. The former have high sensitivity and the latter high specificity for predicting functional recovery. METHODS: Nineteen patients underwent thallium-201 and 99m-technetium tetrofosmin myocardial perfusion imaging, and dobutamine magnetic resonance imaging (MRI), prior to coronary bypass grafting. Criteria for predicted hibernation for each technique were defined before operation. Postoperative criteria for scar and true hibernation were also defined. Biopsies were analyzed for myocyte volume fraction (MVF), glycogen deposition and pathologic cell features. RESULTS: Thallium was most sensitive in predicting hibernation (88%) and MRI most specific (84%); and, although there was good agreement between thallium and tetrofosmin (85%), agreement between MRI and thallium (59%) or tetrofosmin (59%) was poor. For each technique, MVF was higher in segments predicted to be hibernating rather than scar (p < 0.05). The MVF was higher where both thallium and MRI predicted hibernation (0.77+/-0.07) than in segments predicted by thallium alone (0.69+/-0.13, p < 0.05). Proven hibernating segments had a higher MVF than scar (0.72+/-0.11 vs. 0.6+/-0.26, p < 0.05). CONCLUSIONS: Preservation of myocyte fraction is an important determinant of functional recovery after revascularization. A higher myocyte fraction is required to maintain contractile reserve than to achieve significant tracer uptake. This explains the higher sensitivity of radionuclide imaging compared with dobutamine MRI in the identification of myocardial hibernation.

Adult↗
PubMed2005

Blunted functional responses to pre- and postjunctional sympathetic stimulation in hibernating myocardium.

Regional reductions in norepinephrine-tracer uptake are found in pigs with hibernating myocardium. Clinical studies would suggest that this is evidence for denervation; however, the functional responses to sympathetic stimulation have not been evaluated, and our previous studies with beta-adrenergic stimulation have not suggested denervation hypersensitivity. Therefore, pigs were chronically instrumented to produce hibernating myocardium characterized by chronic regional dysfunction and histological viability. Open-chest studies were performed to determine changes in regional function in response to both pre- and postjunctional stimulation. Regional segment shortening was reduced at rest in hibernating myocardium compared with controls (13 +/- 3% vs. 27 +/- 3%, P = 0.004). During stellate ganglion stimulation, regional function increased in both groups of animals (P = 0.008 vs. baseline), but the increase in hibernating myocardium was blunted compared with controls (Delta%, 3 +/- 2% vs. 8 +/- 3%, P = 0.04). Similar results occurred with intracoronary tyramine (10 mug/kg). Functional improvement during intravenous epinephrine infusion (0.35 mug.kg(-1).min(-1)) was also blunted in hibernating myocardium compared with controls (Delta%, 7 +/- 1% vs. 15 +/- 2%, P = 0.04). Even when the improvement in function was expressed relative to the reduced baseline, there was no evidence for catecholamine-mediated hypersensitivity in hibernating myocardium. We therefore conclude that functional responses to both pre- and postjunctional sympathetic stimulation are blunted in pigs with hibernating myocardium. In contrast to previous studies of infarcted, denervated, and acutely stunned myocardium, there is no catecholamine-induced hypersensitivity in hibernating myocardium. These data suggest a downregulation in functional responses to stimulation that would protect hibernating myocardium from demand-induced ischemia at the expense of contractile reserve during sympathetic stimulation.

Animals↗
PubMed1997

Nitroglycerin enhances the ability of dobutamine stress echocardiography to detect hibernating myocardium.

BACKGROUND: A biphasic response of wall thickening with initial improvement and subsequent deterioration during dobutamine stress echocardiography (DSE) has been increasingly used for detection of hibernating myocardium. However, the improvement of wall thickening at low-dose DSE may be limited in hibernating myocardium by severe hypoperfusion. Nitroglycerin (NTG) improves myocardial perfusion, reduces oxygen demand, and may enhance low-dose dobutamine to improve wall thickening. METHODS AND RESULTS: A pig model of myocardial hibernation of 24 hours to 7 days was created through severe left anterior descending coronary artery stenosis with coronary flow reductions of approximately 40%, producing severe regional left ventricular dysfunction but no infarction in seven pigs. Myocardial infarction was produced in five pigs with occlusion of the artery. DSE was performed with incremental doses with and without an NTG infusion of 50 to 100 microg/min. In the hibernating group, NTG alone improved wall thickening in the hibernating region modestly from 11.4+/-7.2% at baseline to 19.1+/-7.0%. The improvement was associated with increased regional coronary flow from 0.46+/-0.12 to 0.55+/-0.13 mL x beat(-1) x 100 g myocardium(-1) (P<.05). There was an additive effect of NTG to low-dose (2.5 to 5 microg x kg(-1) x min(-1)) dobutamine on wall thickening in the hibernating region. The improvement of wall thickening of hibernating myocardium with NTG and dobutamine, from 23.7+/-11.1% to 31.1+/-8.9% (P<.001), was associated with an increase in regional coronary flow (P<.01). NTG did not prevent high doses of dobutamine from inducing deterioration of wall thickening in hibernating myocardium. In the infarcted group, no improvement in wall thickening was observed in infarcted regions during NTG infusion, dobutamine infusion, or the combination. CONCLUSIONS: NTG enhances the improvement of wall thickening at low-dose dobutamine and does not prevent high-dose dobutamine from inducing ischemia in hibernating myocardium. Thus, NTG augments the biphasic response of wall thickening and improves the accuracy of DSE for detecting viable myocardium.

Animals↗
PubMed1998

Downregulation of immunodetectable connexin43 and decreased gap junction size in the pathogenesis of chronic hibernation in the human left ventricle.

BACKGROUND: The regional wall motion impairment and predisposition to arrhythmias in human ventricular hibernation may plausibly result from abnormal intercellular propagation of the depolarizing wave front. This study investigated the hypothesis that altered patterns of expression of connexin43, the principal gap junctional protein responsible for passive conduction of the cardiac action potential, contribute to the pathogenesis of hibernation. METHODS AND RESULTS: Patients with poor ventricular function and severe coronary artery disease underwent thallium scanning and MRI to predict regions of normally perfused, reversibly ischemic, or hibernating myocardium. Twenty-one patients went on to coronary artery bypass graft surgery, during which biopsies representative of each of the above classes were taken. Hibernation was confirmed by improvement in segmental wall motion at reassessment 6 months after surgery. Connexin43 was studied by quantitative immunoconfocal laser scanning microscopy and PC image software. Analysis of en face projection views of intercalated disks revealed a significant reduction in relative connexin43 content per unit area in reversibly ischemic (76.7+/-34.6%, P<.001) and hibernating (67.4+/-24.3%, P<.001) tissue compared with normal (100+/-30.3%); ANOVA P<.001. The hibernating regions were further characterized by loss of the larger gap junctions normally seen at the disk periphery, reflected by a significant reduction in mean junctional plaque size in the hibernating tissues (69.5+/-20.8%) compared with reversibly ischemic (87.4+/-31.2%, P=.012) and normal (100+/-31.5%, P<.001) segments; ANOVA P<.001. CONCLUSIONS: These results indicate progressive reduction and disruption of connexin43 gap junctions in reversible ischemia and hibernation. Abnormal impulse propagation resulting from such changes may contribute to the electromechanical dysfunction associated with hibernation.

Adult↗
PubMedDate not supplied

Mammalian hibernation: lessons for organ preparation?

The adaptations to low environmental temperatures exhibited in mammalian hibernation are many and varied, and involve molecular and cellular mechanisms as well as the systematic physiology of the whole organism. Natural torpidity is characterised by a profound reduction in body temperature and other functions lasting from a few hours to several weeks. Controlled reduction of heart rate, respiration and oxygen consumption is followed by the fall in body temperature. However, thermoregulation persists such that a decrease in ambient temperature below dangerous levels typically triggers arousal, and shivering and non-shivering thermogenesis from brown fat provide the heat to restore body temperature to normal levels. Many of the cellular mechanisms for survival are similar to those brought into play during medium-term storage of organs destined for transplantation. For example maintenance of ionic regulation and membrane fluxes is fundamental to cell survival and function at low body temperatures. Differences between hibernating and non-hibernating species are marked by differences in Na+/K+ transport and Ca++pumps. These in turn are probably associated with alterations in the lipoproteins of the plasma membrane and inner mitochondrial membrane. We have accordingly conducted a series of pilot studies in captured Richardson's ground squirrels kept in laboratory conditions as a model for hypothermic organ preservation. Tissue function was compared during the summer (non-hibernating season) with that in the winter when the animals could be: (i) in deep hibernation in a cold chamber at 4 degree C; (ii) maintained in an ambient temperature of 4 degree C but active and awake; or (iii) active at an ambient temperature of 22 degree C. The studies involved: whole animal monitoring of standard physiological parameters; whole organ (kidney) storage and transplantation for viability assessment; storage and functional assessment on an ex vivo test circuit with capacity for perfusion at normothermic and hypothermic temperatures; measurement of thyroid function; measurements of total nucleotides (ATP, ADP and AMP)and ratios by standard techniques after freeze-clamping of organs; similar nucleotide and pH measurements using31P-NMR as a non-invasive whole animal technique; and measurement of O2 uptake and gluconeogenesis using isolated renal tubules and isolated hepatocytes. Marked differences in cold tolerance were demonstrated between organs taken from hibernating versus non-hibernating individuals. In particular kidneys transplanted from animals in deep hibernation were capable of withstanding up to 72 hours of cold storage as compared with up to 24 hours in non-hibernating squirrels or in comparable sized rats. Adaptations which might provide valuable clues in our attempts to better preserve human organs for transplantation are explored in some depth in this report.

Journal Article↗
PubMed1994

[Postinfarction hibernating myocardium].

The detection of hibernating myocardium after infarction is important because it justifies the discussion concerning the revascularisation of infarcted zones irrigated by occluded or severely stenosed vessels, but with an adequate collateral circulation to allow hibernation. The detection of hibernating myocardium is particularly important in patients without the classical indications for revascularisation, such as residual spontaneous ischaemia or ischaemia provoked by exercise or pharmacological stress testing. All techniques currently in use tend to overestimate the size of the necrosed, fibrous scar, compared with the amount of viable myocardium. Improved regional myocardial function after revascularisation is the most convincing proof of hibernating myocardium but it can only be obtained retrospectively. The detection of a reserve of contractility in the necrosed territory by an inotropic stimulus is well adapted to the demonstration of stunned myocardium but this method has not been proved in hibernating myocardium. Thallium scintigraphy is certainly useful in the prospective diagnosis of hibernating myocardium but the protocol of examination should be adapted to this specific problem. There is little available data concerning the evaluation of hibernating myocardium by positron emission tomography: the technical advantages of this method in assessing myocardial viability should enable a more accurate evaluation of post-infarction hibernating myocardium. Adequate revascularisation of necrosed territories depends on a deeper understanding and more precise prospective assessment of postinfarction hibernating myocardium.

Humans↗
PubMed1997

Ultrastructure of the adrenal cortex of hibernating, arousing, and euthermic dormouse, Muscardinus avellanarius.

BACKGROUND: The adrenal gland is a key organ for hibernation (a condition characterized by striking reduction of body functions). Very limited information is available on the fine structure of the gland during hibernation and on the periodical arousal from hibernation. METHODS: Dormice (Muscardinus avellanarius) were maintained in an external animal house and allowed to hibernate spontaneously (November). Arousal was induced in March by exposure to daylight. Euthermic, active dormice were captured in June. The adrenals were taken from four hibernating, three arousing, and four euthermic dormice and processed for resin embedding. The ultrastructure of the adrenal cortex was investigated by transmission electron microscopy. RESULTS: In the zona glomerulosa of hibernating and arousing dormice, the smooth endoplasmic reticulum was prominent in comparison with euthermic animals, and mitochondria showed abundant vesicular cristae. The zona fasciculata and zona reticularis did not show consistent differences, apart from a lower cell lipid content in the outer portion of zona fasciculata of arousing dormice. CONCLUSIONS: The zona glomerulosa showed signs of increased activity during hibernation. This finding is supported by previous biochemical data demonstrating increased production of renin and aldosterone during such extreme physiological conditions. Activation of the zona glomerulosa in hibernation is probably adaptive to a condition of drastically reduced salt intake.

Adrenal Cortex↗
PubMed2000

Hibernation induces oxidative stress and activation of NK-kappaB in ground squirrel intestine.

Dramatic changes in blood flow occur during torpor-arousal cycles in mammalian hibernators that could increase the risk of oxidative stress to sensitive tissues. We used 13-lined ground squirrels (Spermophilus tridecemlineatus) to determine the effect of hibernation on lipid peroxidation and expression of stress-activated signaling pathways in the intestine, a tissue highly susceptible to ischemia-reperfusion injury. Compared with summer-active squirrels, levels of the mitochondrial stress protein GRP75 were consistently higher in intestinal mucosa of hibernators in each of five hibernation states (entrance, short-bout torpid, long-bout torpid, arousal and interbout euthermia). The redox-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB), was strongly activated in each hibernation state compared with summer squirrels except for squirrels during an arousal from torpor. In contrast, NF-kappaB activation in brown adipose tissue (BAT) was low in active and hibernating squirrels regardless of season. Levels of conjugated dienes (products of lipid peroxidation) were higher in intestine of hibernators entering torpor and early in a torpor bout compared with summer squirrels. Conjugated diene levels were also higher in short-bout torpid vs arousing squirrels. The results suggest that the intestinal mucosa is vulnerable to oxidative stress during the hibernation season and in response may activate cellular defense pathways that help minimize severe oxidative damage induced by torpor-arousal cycles.

Animals↗
PubMed2002

Body temperature patterns before, during, and after semi-natural hibernation in the European ground squirrel.

Ground squirrels undergo extreme body temperature fluctuations during hibernation. The effect of low body temperatures on the mammalian circadian system is still under debate. Using implanted temperature loggers, we recorded body temperature patterns in European ground squirrels kept in an enclosure under natural conditions. Although hibernation onset was delayed, hibernation end corresponded closely to that measured in a field population. Circadian body temperature fluctuations were not detected during deep torpor, but indications of circadian timing of arousal episodes at higher temperatures were found at the beginning and end of hibernation. One male exhibited synchronised arousals to a relatively constant phase of the day throughout hibernation. All animals first entered torpor in the afternoon. Daily body temperature fluctuations were decreased or distorted during the first days after hibernation. We hypothesise that hibernation may affect the circadian system by either decreasing the expression of the circadian oscillator, or by decreasing the amplitude of the circadian oscillator itself. possibly due to gradual, temperature dependent, internal desynchronisation. The latter mechanism may be beneficial because it might facilitate post-hibernation re-entrainment rates.

Animals↗
PubMed1986

Hippocampal and cortical opioid receptor binding: changes related to the hibernation state.

In vitro opioid receptor binding in the dorsal hippocampal formation and parietal cortex was surveyed in ground squirrels (Citellus lateralis) in the contrasting physiological states of hibernation and euthermia (i.e. not hibernating). Computer-assisted autoradiographic analysis of coronal sections incubated with [3H]dihydromorphine (DMH; 4 nM) revealed statistically significant reductions in specific opioid binding associated with hibernation. In the dorsal hippocampal formation of hibernating animals, binding in the stratum radiatum of CA3, hilus of the dentate gyrus and molecular layer of the dentate gyrus exhibited decreases up to 34% compared to euthermic animals. The stratum radiatum of CA3 exhibited the smallest decrease overall. DHM binding in parietal cortex displayed significant hibernation-related reductions, although they were not uniformly observed across all laminae at the 3 different brain levels examined. These experiments present evidence of changes in brain opioid binding related to the mammalian state of hibernation. The results suggest that changes in opioid receptor binding during hibernation may contribute to the earlier reported apparent failure of morphine physical dependence to develop during hibernation.

Animals↗
PubMed1990

Suprachiasmatic nuclei influence hibernation rhythms of golden-mantled ground squirrels.

Hibernation and body mass rhythms were studied in 13 golden-mantled ground squirrels maintained in an LD 12:12 photoperiod at 5 degrees C. Complete or partial ablation of the suprachiasmatic nuclei (SCN) disrupted normal hibernation rhythms. Over the course of 2 years, several animals progressed through 4 hibernation cycles, one squirrel manifested two abnormally long hibernation seasons, and another failed to hibernate. Squirrels with intact SCN exhibited normal circannual hibernation rhythms at intervals of 11.5 +/- 0.3 months. Hibernation coincided with the weight loss phase of the body mass cycle in control squirrels, but these two rhythms were dissociated in animals with lesions of the SCN. The annual plasma testosterone rhythm was normal or slightly phase-delayed in squirrels with SCN lesions maintained at 23 degrees C. The SCN may be part of a neural circuit that mediates circannual organization of hibernation rhythms.

Animals↗
PubMed1991

Seasonal changes in methionine-enkephalin immunoreactivity in the brain of a hibernator, Spermophilus columbianus.

To identify the actual location of central endogenous opioid systems which may be involved in regulating the hibernation cycle, differences in the pattern of central methionine-enkephalin (Met-EK) immunoreactivity were compared between hibernating (body temperature, Tb = 7 degrees C) and non-hibernating (Tb = 37 degrees C) Columbian ground squirrels using the peroxidase-antiperoxidase technique. In non-hibernating animals, Met-EK-immunoreactive perikarya were observed in telencephalic (putamen, caudate nucleus, medial septum-diagonal band complex, amygdala) and diencephalic (periventricular hypothalamic nucleus, lateral hypothalamic area) regions, whereas immunoreactive fibers were found in the lateral septum, stria terminalis nucleus, various hypothalamic areas, arcuate nucleus, median eminence, thalamic intralaminar, periventricular nucleus and lateral habenular nucleus. Compared to the non-hibernating animal, a marked increase in the number of Met-EK-immunoreactive fibers was found in the lateral septal nucleus, the periventricular nucleus, the intralaminar thalamus and the paraventricular hypothalamus of hibernating ground squirrels. Since these changes in immunoreactivity were not observed in the artificially induced hypothermic ground squirrels (Tb = 7 degrees C), it is unlikely that the dissimilarity in immunoreactivity between animals from different hibernating phases is due to differences in their Tb. In combination with our previous studies, these results tend to suggest that hibernation may be brought about by an increase in endogenous opioid activity, especially in the lateral septal region.

Animals↗
PubMed1983

Ambient temperature dependence of the body temperature and of the duration of the hibernation periods in the garden dormouse, Eliomys quercinus L.

Hibernation pattern in the garden dormouse (Eliomys quercinus) was studied at TA's of 0, 4, 6.5, and 9 degrees C during 6 months in each study winter. The animals were kept in darkness without food or water. Body temperature and the mean duration of the hibernation periods were ambient temperature dependent. The comparison of hibernation at different TA's was based on three features: the mean duration of the hibernation periods during the midwinter plateau, the existence of the initial and terminal phases with the changing length of the hibernation periods, and the differences between the sexes. The TA of 4 degrees C was the optimal TA for long-term hibernation. The difference between 4 degrees C and other TA's was greater in males. The TA's of 0 and 9 degrees C were near the lower and higher TA limits for long-term hibernation. Signs of the existence of a circannual rhythm were detected in the males toward the end of the hibernation season.

Animals↗
PubMed1987

Altered tyrosine and tryptophan metabolism during hypothermic hibernation in the 13-lined ground squirrel (Spermophilus tridecemlineatus).

(1) Tyrosine and tryptophan metabolism in brain and peripheral tissues were studied in hypothermic hibernating and normothermic nonhibernating 13-lined ground squirrels (Spermophilus tridecemlineatus). (2) In the hypothermic hibernating state, there were significant elevations of brain stem tyrosine, norepinephrine, and dopamine levels; forebrain norepinephrine and dopamine levels; and cerebellum norepinephrine and tyrosine levels. (3) On the other hand, plasma norepinephrine levels were significantly decreased in hypothermic hibernating squirrels while plasma tyrosine levels were increased. Kidney norepinephrine levels were significantly increased in hypothermic hibernating squirrels, while kidney tyrosine levels were decreased. Total plasma tryptophan and free plasma tryptophan were significantly reduced in hypothermic hibernating squirrels. Hepatic tyrosine aminotransferase Km and Vmax were decreased in hypothermic hibernating squirrels, while tryptophan 2,3-dioxygenase activity was not altered. Plasma and liver albumin were increased in hypothermic hibernating squirrels, while plasma and liver total protein were not altered. (4) These results demonstrate that significant changes in tyrosine and tryptophan metabolism occur in both central and peripheral tissues with concomitant alterations in metabolites during hypothermic hibernation in 13-lined ground squirrels.

Animals↗
PubMed1993

The modulatory effects of mu and kappa opioid agonists on 5-HT release from hippocampal and hypothalamic slices of euthermic and hibernating ground squirrels.

To elucidate the role of opioids in regulating hibernation, the modulatory effects of different opioids on 35 mM K(+)-stimulated [3H]-5-HT release from brain slices were examined in the Richardson's ground squirrels. DAGO ([D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin), a specific mu agonist, evoked a significant dose-dependent (10(-7)-10(-5) M) inhibition of K(+)-stimulated 5-HT release from hippocampal slices of the non-hibernating squirrels. The inhibitory effect of DAGO was attenuated by either the opioid antagonist naloxone (10(-6) M) or the voltage dependent sodium channel blocker tetrodotoxin (TTX, 10(-6) M). The inhibitory effect of DAGO persisted in the hibernating squirrels; however, a ten fold higher concentration of DAGO (10(-6)-10(-5) M) was required to elicit a significant inhibition. In contrast, kappa agonist U50488 (10(-5) M) exerted a significant enhancement of K(+)-stimulated 5-HT release from hippocampal slices of the non-hibernating squirrels. This enhancement was blocked by either the specific kappa antagonist nor-binaltorphimine (10(-6) M) or TTX (10(-6) M). However, in the hibernating squirrels, the stimulatory effect of U50488 (10(-5) M) on 5-HT release was absent. DAGO and U50488 had no modulatory effects on K(+)-stimulated 5-HT release from the hypothalamic slices of either the non-hibernating or hibernating squirrels. These results demonstrate that the modulatory effects of opioids on 5-HT release are receptor-specific and state-dependent, indicating the complex nature of the roles of different opioids in regulating hibernation.

Amino Acid Sequence↗
PubMed1982

Seasonal variation in thyrotropin-releasing hormone (TRH) content of different brain regions and the pineal in the mammalian hibernator, Citellus lateralis.

We have measured the endogenous TRH concentration in the pineal and 9 brain regions of a seasonal hibernator, the golden-mantled ground squirrel, during euthermia and hibernation in order to investigate the possibility that changes in TRH concentration might occur in association with naturally-occurring changes in CNS-mediated physiological and behavioral processes. Regional TRH content was assessed by radioimmunoassay in adult animals that were killed during euthermia in the mid-portion of each season and during hibernation in mid-winter. No significant changes in TRH concentration related to season or to hibernation versus euthermic state were noted in the hippocampus, brainstem, or cerebellum. In the olfactory bulb, preoptic area, and pineal, seasonal variation within euthermic groups was evident. During hibernation, statistically significant decreases in TRH content occurred in the forebrain, olfactory bulb, hypothalamus, septum, preoptic area, and midbrain. Significant fluctuations during hibernation were also observed in the pineal. In this structure, TRH concentration varied in relation to the phase of the hibernation bout. TRH content in the last quarter of the bout was three times greater when compared to values observed in the first quarter of the bout. These results suggest that TRH may be involved in the control processes attributed to these regions and support a role for TRH in the neural control of hibernation.

Animals↗
PubMed1986

Prostaglandin E1 (PGE1) stimulates in vitro renin release in the hibernating ground squirrel.

Using a renal cortical slice preparation obtained from hibernating ground squirrels, this study investigated whether three major intrarenal prostaglandins (PG) and other agents added at a 10(-5) M dose can affect renin release (RR), and if their effect on RR is correlated with changes in tissue cyclic AMP content (tcAMPc). Resting in vitro levels for RR and tcAMPc during hibernation were found to be comparable to those observed in non-hibernating (NH) mammals. Addition of PGE1 significantly stimulated RR while PGE2 and PGF2-alpha were ineffective. None of the three PG's tested altered resting levels of tcAMPC. When added by itself or in conjunction with any of the three PG's, the phosphodiesterase inhibitor theophylline did not modify resting levels of RR and tcAMPc, but it prevented the previous stimulatory effect of PGE1 alone on RR. Addition of lipid-soluble dcAMP, either alone or in conjunction with any of the three PG's, resulted in an increase in tcAMPc in all instances, no change in resting RR regarding PGE2 and PGF2-alpha, and again the prevention of the stimulatory effect of PGE1 alone on RR. These data suggest that: the resting activity of the renin-angiotensin system (RAS) and the adenylate cyclase-cAMP system (AC-cAMP) of the hibernating ground squirrel is comparable to that of NH species; in contrast, the sensitivity of the RAS of the hibernator to PG stimulation is less than that exhibited by the RAS of NH species when comparable in vitro concentrations of three major PG's are used; PGE1 stimulation of RR in the hibernator is independent of changes in tcAMPc; changes in tcAMPc may be inversely related to those in RR in the hibernator; and the known stimulatory effect of PG's on the renal cortical AC-cAMP of NH species is not seen in the hibernating ground squirrel at comparable PG doses.

Adenylyl Cyclases↗
PubMed1995

Characterization of muscle glyceraldehyde-3-phosphate dehydrogenase isoforms from euthermic and induced hibernating Jaculus orientalis.

The specific activity of D-glyceraldehyde-3-phosphate (G3P) dehydrogenase (phosphorylating) (GPDH, EC 1.2.1.12) found in skeletal muscle of induced hibernating jerboa (Jaculus orientalis) was 3-4-fold lower than in the euthermic animal. The comparative analysis of the soluble protein fraction of these tissues by SDS-PAGE and Western blotting showed a significant decrease in the intensity of a protein band of about 36 kDa, the GPDH subunit, in hibernating jerboa. After using the same purification procedure, the GPDH from muscle of hibernating jerboa exhibited lower values for both apparent optimal temperature and specific activity than the enzyme from the euthermic animal. Non-linear Arrhenius plots were obtained in both cases, but the Ea values calculated for the GPDH from hibernating tissue were higher. Although in both purified enzyme preparations three isoelectric GPDH isoforms, exhibiting pI values in the range 8.2-7.5, were resolved by chromatofocusing, clear differences were observed in these preparations concerning the relative contribution to the total enzymatic activity of the two main isoforms, named GPDH I (pI values, 8.1-8.2) and GPDH II (pI values, 7.8-7.9). Thus, whereas GPDH I was the major isoform purified from euthermic muscle, accounting for more than 90% of the total activity, the amount of activity due to GPDH II reached up to 65% in preparations of hibernating jerboa. All isoforms exhibited similar native and subunit molecular masses and cross-reacted with an anti-GPDH antibody raised against the GPDH I. However, the two muscle GPDH isoforms prevailing under hibernating conditions exhibited a decreased catalytic efficiency when compared with the corresponding major isoforms purified from euthermic animals, as indicated by their different specific activities and kinetic parameters, i.e. relatively high Km and low Vmax values. Since the glycolytic flow has been found to be widely reduced in skeletal muscle of induced hibernating jerboa, the changes in the GPDH isoforms described in the present study could provide a molecular basis to explain some of the metabolic changes associated with mammalian hibernation.

Animals↗