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PubMed1987

Effects of photoperiod on hibernation in castrated Turkish hamsters.

Hibernation and circulating reproductive hormones [luteinizing hormone, follicle-stimulating hormone, and prolactin (LH, FSH, and PRL)] were studied for greater than 40 wk in castrated male Turkish hamsters (Mesocricetus brandti) housed in either a long-day cold or short-day cold environment. A significantly greater percentage of short-day animals hibernated than did long-day animals, indicating that short-day exposure can predispose Turkish hamsters to enter hibernation and that this photoperiodic effect cannot be explained entirely by the inhibitory influence of short days on testicular endocrine activity. Long-day castrates showed no significant changes in LH or FSH levels during the experiment. In the short-day castrates serum LH, FSH, and PRL levels were reduced after 4-9 wk and increased again after 18-23 wk of short-day exposure. The hibernation season ended after 30-34 wk on short days, several weeks later than in testis-intact males studied previously. These results indicate that gonadal factors are not required for the termination of hibernation but may influence its timing. The resumption of FSH secretion occurred no later during short-day exposure in castrated hibernators than in the preceding study of testis-intact, short-day males hibernating in the cold or those held at room temperature. Thus the endogenous timing mechanism regulating the reactivation of the hypothalamopituitary axis toward the end of the winter season is apparently gonad independent and is little affected by the low body temperatures experienced during hibernation.

Animals↗
PubMed1990

Testosterone influences hibernation in golden-mantled ground squirrels.

At different phases of the hibernation season, castrated male golden-mantled ground squirrels were implanted with capsules that either were filled with testosterone (T) or left empty (blank). Blank-treated animals hibernated normally when housed at 5 degrees C. Entry into hibernation was prevented in the majority of squirrels treated with T several days before the initial cold challenge. T concentrations that inhibited torpor (greater than 1.2 ng/ml) were comparable with those of intact males at the end of the hibernation season. In some squirrels, moderate T concentrations were compatible with hibernation, but torpor bout duration was shorter than normal. The inhibitory effect of T on hibernation did not appear to require aromatization of T to estradiol. We suggest that a steroid-independent mechanism triggers arousal from hibernation and that T-dependent processes determine whether hibernation is resumed at the end of an arousal period.

Animals↗
PubMed1992

Maintenance of intestinal nutrient transport during hibernation.

We studied nutrient absorption across the brush-border membrane in jejunal tissues from active 13-lined ground squirrels and in hibernating squirrels that had not eaten for at least 6 wk. Body weights and jejunal wet weights per centimeter were significantly reduced in the hibernators. Rates of total and carrier-mediated uptake of 3-O-methylglucose (3-OMG) per centimeter intestinal length were greater in the active squirrels, but 3-OMG uptakes per milligram intestinal weight were greater in the hibernators, due to a significantly greater maximum rate of uptake (Jmax) per milligram with no differences in apparent Michaelis constant (Km). Passive permeabilities to L-glucose were similar in both groups. Total uptake of L-proline per centimeter was greater in active squirrels, but total proline uptake per milligram was greater in the hibernators due to a significantly greater Jmax per milligram with no difference in apparent Km. Na(+)-independent proline uptake accounted for a greater proportion of total proline uptake in active compared with hibernating squirrels. As a consequence, Na(+)-dependent proline uptake was greater in the hibernators when uptake was normalized either to intestinal length or intestinal weight. Thus hibernation is associated with an increase in the Jmax per milligram for 3-OMG and proline transport, as well as a shift in the Na+ dependency of proline uptake. We conclude that nutrient absorption is selectively retained in mammalian hibernators to maintain transport function after the extended winter fast.

3-O-Methylglucose↗
PubMed1996

Temperature sensitivity of sleep homeostasis during hibernation in the golden-mantled ground squirrel.

Brain temperature (Tbr), vigilance state, and electroencephalograph slow-wave activity (EEG SWA, 1.0-4.0 Hz) were measured during hibernation and spontaneous arousals to euthermia in seven golden-mantled ground squirrels (Spermophilus lateralis). Animals were held at air temperatures (Ta) ranging from 6 to 21 degrees C. SWA was used as a measure of the intensity of non-rapid eye movement (NREM) sleep. Squirrels that had hibernated at high Ta had lower SWA in NREM sleep in the hours following arousal than when they hibernated at low Ta. SWA in NREM sleep during euthermia immediately following arousal was significantly correlated to minimum Tbr and SWA during hibernation. The duration of the preceding hibernation bout had no significant effect on SWA during euthermia. We hypothesize that the restorative process of sleep, reflected by SWA, is temperature sensitive and is compromised by the low temperatures in hibernation. The accumulation of a SWA debt during hibernation may be related to the temperature-dependent depression of SWA during hibernation.

Animals↗
PubMed2003

Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature.

Mammalian hibernators undergo a remarkable phenotypic switch that involves profound changes in physiology, morphology, and behavior in response to periods of unfavorable environmental conditions. The ability to hibernate is found throughout the class Mammalia and appears to involve differential expression of genes common to all mammals, rather than the induction of novel gene products unique to the hibernating state. The hibernation season is characterized by extended bouts of torpor, during which minimal body temperature (Tb) can fall as low as -2.9 degrees C and metabolism can be reduced to 1% of euthermic rates. Many global biochemical and physiological processes exploit low temperatures to lower reaction rates but retain the ability to resume full activity upon rewarming. Other critical functions must continue at physiologically relevant levels during torpor and be precisely regulated even at Tb values near 0 degrees C. Research using new tools of molecular and cellular biology is beginning to reveal how hibernators survive repeated cycles of torpor and arousal during the hibernation season. Comprehensive approaches that exploit advances in genomic and proteomic technologies are needed to further define the differentially expressed genes that distinguish the summer euthermic from winter hibernating states. Detailed understanding of hibernation from the molecular to organismal levels should enable the translation of this information to the development of a variety of hypothermic and hypometabolic strategies to improve outcomes for human and animal health.

Adaptation, Physiological↗
PubMed1998

The disappearing slow wave activity of hibernators.

High and monotonically declining levels of EEG slow wave activity (SWA) occur following arousal from hibernation. Similar profiles of SWA occur in mammals including humans during sleep following periods of prolonged wakefulness, and have been interpreted as reflecting a homeostatic process regulating NREM sleep. It was proposed that even though hibernation appears to be an evolutionary extension of NREM sleep, the low brain temperatures during hibernation are not compatible with sleep restorative processes, and therefore sleep debt accumulates during hibernation and may be a factor triggering periodic arousal. In the present study, golden-mantled ground squirrels were sleep deprived by gentle handling following arousal from hibernation. If the SWA peaks following bouts of hibernation reflect a homeostatic response to an accumulated sleep debt, sleep deprivation should simply displace the SWA which would then occur, and be augmented, during subsequent sleep. In contrast, when animals were sleep deprived following arousal from hibernation, the anticipated SWA peak did not occur during subsequent sleep. It is suggested that the SWA following arousal from hibernation does not represent homeostatic regulation of NREM sleep, but instead some other neurological process involved in the recovery of brain function from an extended period at low temperature.

Adaptation, Physiological↗
PubMedDate not supplied

[Effect of chronic disconnection between septal area and hypothalamus on modulation of background activity of septal neurons by biologically-active substances in hibernators].

Our previous work demonstrated paradoxically increased excitability of the medial septal (MS) neurons during hibernation of ground squirrels in comparison to waking animals. Recently this was supported by demonstration of higher efficacy of the neuropeptides identified in the brain of hibernators in septal slices of hibernating animals. To decide whether this increased excitability is determined by endogenous properties of the pacemaker septal neurons, or it depends on the influences of thermoregulatory-circadian mechanisms of preoptico-hypothalamic area, testing of the neuropeptides (TSKYR, TSKY, DY) and neurotransmitters participating in control of hibernation (serotonin and noradrenaline) was repeated on septal slices taken from the brain of hibernating animals two weeks after operation disconnecting it from the hypothalamus. Effects of neuropeptides in the deafferented hibernating animals neither quantitatively (low reactivity level), nor qualitatively (distribution of inhibitory and excitatory responses) differed from the data obtained in waking animals. Decrease of reactivity occurred at the expense of the neurons with regular pacemaker-like spontaneous activity. Thus, increased reactivity of the MS neurons to neuropeptides in hibernating animals depends mainly on influence of the hypothalamic centres controlling hibernation behavior upon pacemaker neurons of the MS. Contrary to the neuropeptides, serotonin and noradrenaline were highly effective in deafferented septum. They evoked stronger changes of background activity (shorter latencies and more rapid development of maximal shifts), presumably as a result of development of denervation hypersensitivity after deafferentation.

Animals↗
PubMedDate not supplied

[In vitro viability and glutathione levels in mesencephalic neurons after seven days hibernation].

In embryonic mesencephalic transplant in patients with Parkinson s disease dopaminergic survival is low (5 10%), and for this reason the use of multiple donors has been considered. The difficulty of obtaining more tissue determines the need for a procedure that enables human nigral tissue to be stored for a time without affecting its physiological state in any significant way. This study was designed to determine whether hibernation of tissue fragments has any influence on viability, how the viability of the mesencephalic cells behaves after 7 days hibernation and the glutathione levels in the hibernated tissue (HT). The viability of the HT in pieces (82.37 2.12) was found to be higher than the value for the whole mesencephalon (70.29 3.43). Viability of the HT, seven days at 4 C, at different post dissociation times, did not differ significantly. Despite the significant differences found between hibernated and fresh tissue at t= 0, this procedure does not seem to affect the mesencephalic tissue in any significant way, as it conserved a 94% viability after hibernation. No evidence was found of increased glutathione content as an antioxidizing response to the damage that might be caused by hibernation. These results suggest that since hibernation does not have any significant effect on the state of the cells it could be considered a useful procedure for conserving tissue to be used in clinical transplants. Moreover, further research is needed on survival and functionality of hibernated cells after being transplanted into animal models in order to evaluate their potential for use in cell therapy.

Animals↗
PubMed2003

Mammalian hibernation. Transcriptional and translational controls.

Mammalian hibernation is an amazing strategy for winter survival. Animals sink into a deep torpor where metabolic rate is < 5% of normal, body temperature falls to 0-5 degrees C, and physiological functions are strongly suppressed. Hibernation is a closely regulated process that includes multiple controls on gene transcription and protein translation, the primary subjects of this review. Recent studies by our lab and others have used multiple techniques of gene discovery, including cDNA array screening, to identify genes that are up-regulated in hibernation and continuing studies are tracing the functions of the encoded proteins and the signal transduction systems that regulate expression. For example, up-regulation of fatty acid binding proteins during hibernation facilitates the switch to a primary dependence on lipid fuels by nearly all organs and new studies have shown that up-regulation is mediated by the PPARgamma transcription factor and its co-activator, PGC-1. Several hypoxia-related genes including HIF-1alpha are also up-regulated during hibernation suggesting a role for this transcription factor in mediating adaptive responses for hibernation. Controls on mRNA translation during hibernation accomplish two goals: a general strong suppression of protein synthesis that contributes to energy savings and the selected synthesis of a few specific proteins. These goals are accomplished by mechanisms that include reversible phosphorylation controls on ribosomal initiation and elongation factors and differential distribution of individual mRNA species between polysome and monosome fractions. Studies of gene expression, protein synthesis regulation, controls on fuel metabolism, and signal transduction pathways are combining to produce an integrated model of the biochemical regulation of hibernation.

Animals↗
PubMed2003

[The annual involution and regeneration of the thymus in hibernating animals and perspectives of its studies in gerontology and stem cell proliferation].

Data on a unique phenomenon of annual involution and neogenesis of thymus gland in hibernating animals are reviewed. In accordance with morphological findings, the annual thymus involution in hibernating animals is close to the age-dependent thymus involution occurring in all mammals once in a lifetime. In opposite, thymus involution in hibernating animals is totally different from the accidental involution. During hibernation, the thymus tissue is substituted by the brown fat tissue. In the spring, thymus gland neogenesis stats with intensive growth of epithelial tissue followed by lymphocyte infiltration and exhaustion of brown tissue. Morphological changes in the thymus gland within the annual cycle were compared with seasonal dynamics of structural and functional changes in peripheral lymphoid organs (spleen, lymphoglandular, peritoneal fluid). A general regularity was observed involving a decreased functional activity of immune cells in autumn, its sharp depression during winter hibernation, and obvious increase in summer with the onset of a season of animal activity. It is supposed that a sharp increase in the tumor necrosis factor (TNF) production observed during short-term awakenings in winter may serve an important link in this unique immune adaptation mechanism. The season changes in cellular TNF secretion suggest a mobilization of protective resources in hibernating animals in autumn and winter, i.e. in seasons when the thymus gland activity is depressed. The annual involution of thymus gland cannot be related to droppings in the environmental or body temperatures, as it comes long before their fall. Additionally, it is not related to ageing, as it occurs already in young hibernating animals. The role of hormones, including melatonine and corticosteroids, in mechanisms regulating thymus gland involution in hibernating animals is discussed.

Adaptation, Physiological↗
PubMed1987

Regulation of liver metabolism by enzyme phosphorylation during mammalian hibernation.

Kinetic properties of regulatory enzymes of glycolysis in liver of the mouse, Zapus hudsonius, were modified during hibernation, the probable mechanism being covalent modification. Liver glycogen phosphorylase activity was strongly depressed during both short (less than 24 h) and long (5-8 days) term hibernation, the mechanism involving a decrease in both the percentage of enzyme in the active a form and the total amount (a + b) of enzyme expressed. Phosphofructokinase showed kinetic changes (a 2.5-fold increase in Ka for fructose-2,6-P2, 4- and 3.7-fold decreases in I50 values for ATP and citrate, compared to euthermic controls) in liver of hibernators indicative of phosphorylation inactivation of the enzyme. Measured levels of fructose-2,6-P2 in liver did not change during hibernation. Changes in pyruvate kinase kinetics in liver from long term hibernators similarly indicated enzyme phosphorylation in the depressed state (Ka for fructose-1,6-P2 increased 4.4-fold, I50 for L-alanine decreased 6.3-fold). Apparent covalent modification of glycolytic enzymes during hibernation may serve two functions: depression of glycolytic activity as part of the general metabolic rate depression of hibernation, or reorganization of fuel use in the hibernating state to limit carbohydrate catabolism and promote gluconeogenesis.

Adenosine Triphosphate↗
PubMed1980

Protein metabolism and urea recycling in rodent hibernators.

A review of the metabolism of hibernators supports the argument that protein utilization is an essential aspect of hibernation. Several lines of evidence in support of this hypothesis are discussed, including (1) the field preferences of some hibernators for a diet rich in protein prior to hibernation, (2) the gluconeogenic maintenance of glycogen stores during hibernation, (3) the maintenance of plasma amino acid levels during hibernation and their elevation during the process of arousal, (4) changes in levels of nonprotein nitrogen with hibernation, (5) the potential for urea recycling by intestinal microflora in active fasted animals, and (6) the lack of correlation between loss of lean body mass and urea recovery during the hibernating season. These data serve to emphasize the contribution of protein metabolism to the overall energetic adjustments required for survival at a lower body temperature.

Amino Acids↗
PubMed1998

Hibernating myocardium: its pathophysiology and clinical role.

Myocardial hibernation, as first defined by Rahimtoola, is a state of chronic contractile dysfunction in patients with coronary artery disease which is fully reversible upon reperfusion. Clinical conditions consistent with the existence of myocardial hibernation include unstable and stable angina, myocardial infarction heart failure, and anomalous origin of coronary arteries. The mechanisms of hibernation are not known. Morphological alterations have been described in the hibernating area of patients, but these information are strongly affected by the diagnostic criteria utilized to screen patients. It has been postulated that hibernation is an adaptive phenomenon occurring during ischemia. In this context, downregulation of contraction is not regarded as a consequence of energetic deficit, but as a regulatory event aimed at reducing energy expenditure, thereby maintaining integrity and viability. Thus, hibernation might bear a relationship to the phenomenon of low-flow perfusion-contraction matching, or repetitive stunning or preconditioning. Clear-cut evidence for the mechanism of hibernation in the clinical setting seems likely to remain elusive, because of the nature of the studies needed to document it. Current experimental evidence supports the view that hibernation, stunning, preconditioning, or their coexistence can be responsible for regional myocardial contractile dysfunction which is reversible upon reperfusion. These are all adaptive and protective phenomena independent of their terminology and strict definitions and do not always apply to the extremely complex situation of myocardial ischemia in man.

Adaptation, Physiological↗
PubMedDate not supplied

Myocardial hibernation.

From available results, the following schematic can be drawn: Reductions in perfusion pressure are not associated with impaired ventricular function as long as they take place within the autoregulatory range. Additional reductions in perfusion pressure that moderately diminish coronary blood flow will result in a particular ischemia with decreased but stable function: perfusion and contraction match, the myocardium hibernates. The process responsible for this new equilibrium could be termed down regulation of function. The trigger inducing hibernation is so far unknown. The strategy, however, is similar to that used by hibernating animals. Likewise, myocardial hibernation is a protective mechanism. As hibernators recover initial function after unfavourable periods are terminated, hibernating myocardium recovers after institution of physiologic perfusion. It is under debate, whether function quickly recovers or remains temporarily depressed. As hibernating animals might finally even die, if unfavourable periods last too long, myocardium might become irreversibly injured due to ischemia lasting too long. Additional reductions in perfusion pressure and oxygen supply below the hibernating range produce ischemia in the more classical sense, because oxygen supply and demand no longer match. Damage will become irreversible in case the situation persists longer than about 20 min. After onset of reperfusion, the myocardial function would remain depressed, however, for a considerable period: myocardial stunning. Considering the regional heterogeneities of myocardial blood flow, distinct differentiation between moderate and severe ischemia is difficult. Ischemia will induce more articulate damage in subendocardial than in subepicardial layers. Similarly, damage in the ischemic core will be more pronounced than in the border zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium: a pilot study.

BACKGROUND: Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium. METHODS: A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies. RESULTS: A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed. Hibernating myocardium was demonstrated 4 weeks after ameroid placement by DSE. Coronary angiography demonstrated a discrete 90%stenosis in the proximal LAD at the site of ameroid constrictor placement without evidence of collaterals. Using PMR, 17 bursts were successfully delivered to the anterior wall distal to the ameroid constrictor. Four weeks after PMR, there was improvement in wall motion function in the region distal to the ameroid placement by echocardiography. Histopathologic analysis demonstrated the absence of myocardial infarction in the anterior wall distal to the ameroid constrictor. CONCLUSIONS: The performance of PMR in a porcine model of hibernating myocardium is feasible and is associated with an improvement regional wall motion function after 4 weeks.

Animals↗
PubMed2004

Ultrastructural evidence of increased tolerance of hibernating myocardium to cardioplegic ischemia-reperfusion injury.

OBJECTIVES: The goal of this study was to investigate the effects of ischemia-reperfusion on myocardial ultrastructure in patients with and without hibernating myocardium. BACKGROUND: It is generally accepted that chronically dysfunctional, hibernating myocardium may remain nonetheless viable for a long time. It has been postulated that hibernating myocytes may survive, despite being subtended by a severe coronary artery stenosis, as they might be less susceptible to ischemic insults. However, whether hibernating myocardium is indeed more resistant to ischemia has never been investigated. METHODS: Myocardial biopsies were taken before cardiac arrest and after reperfusion from the anterior wall of the left ventricle in patients undergoing coronary artery bypass surgery, divided according to presence (n = 7) or absence (n = 7) of hibernating myocardium. Ultrastructural changes were studied by electron microscopy. Because ischemia-reperfusion injury is related to oxidative stress, we also evaluated coronary sinus concentration of the antioxidants alpha-tocopherol, beta-carotene, and ubiquinol, and of lipid peroxidation products pre-ischemia and after reperfusion. RESULTS: Both groups were similar with respect to length of ischemia and changes in the various indexes of oxidative stress. In normally contracting myocardium, ischemia/reperfusion induced moderate overall ultrastructural changes, and marked alterations at the mitochondrial level. In contrast, post-reperfusion biopsies of hibernating myocardium displayed only minor overall ultrastructural changes, and scored significantly better on mitochondrial damage. CONCLUSIONS: Despite similar severity of ischemia/reperfusion, hibernating myocardium showed significantly less ultrastructural evidence of cell injury compared with normally contracting myocardium. These data indicate that human hibernating myocardium is intrinsically more resistant to ischemia/reperfusion injury.

Aged↗
PubMed2000

An experimental model of chronic myocardial hibernation.

BACKGROUND: Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. METHODS: Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. RESULTS: Positron emission tomography (13N-labeled-ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% +/- 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. CONCLUSIONS: Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart.

Animals↗
PubMed2003

Myocardial blood flow in patients with hibernating myocardium.

The debate on whether resting myocardial blood flow (MBF) to hibernating myocardium is reduced or not has attracted a lot of interest and has contributed to stimulate new research on heart failure in patients with coronary artery disease (CAD). Positron emission tomography with oxygen-15 labeled water (H(2)(15)O) or nitrogen-13 labeled ammonia (13NH(3)) has been used for the absolute quantification of regional MBF in human hibernating myocardium. When hibernating myocardium is properly identified, i.e. a dysfunctional segment subtended by a stenotic coronary artery that improves function upon reperfusion, the following conclusions can be reached based on the available literature: (a) in the majority of these studies resting MBF in hibernating myocardium is not different from either flow in remote tissue in the same patient or MBF in normal healthy volunteers; (b) a reduction in MBF of approximately 20% compared to MBF in remote myocardium or age matched normal subjects has been demonstrated in a minority of truly hibernating segments; (c) hibernating myocardium is characterized by a severely impaired coronary flow reserve which improves after revascularization in parallel with contractile function. Thus, the pathophysiology of hibernation in humans is more complex than initially postulated. The recent evidence that repetitive ischemia in patients with coronary artery disease can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and hibernation are two facets of the same coin.

Animals↗