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PubMed1989

Study of the testis in the active and hibernating hedgehog.

The structure and ultrastructure of the hedgehog's testis has been studied during active and hibernating states. The maximum activity of the hedgehog's testis manifest itself in spring and summer. In autumn they enter in a seasonal resting, in which, the interstitial cells atrophy and it can observe primary spermatocytes resting next to spermatogonia and supporting cells in the seminiferous tubules. These have a minimal diameter and contain only primary spermatocytes in hibernating period also the seminiferous epithelium that compound the walls of the tubules are about 72 microns thick in the active period and about 47 microns in hibernation. The Sertoli cells shows a small diameter in hibernation than in the active season. The nucleus has one or two nucleoli with distinguish themselves from those observed in the active season because of their closer union with the inner nuclear envelope. In autumn (resting period) the interstitial tissue regress and the Leydig cells are aggregated in blocks with little cytoplasm, minimum size nuclei and 1 or 2 nucleolus closely to the inner nuclear membrane. Like then in the ovary, the hedgehog's testis follows a seasonal cycle determined by the temperature and environmental changes and it have a power of physiological adaptation inherent of a typical hibernating animal.

Animals↗
PubMed1987

[Ultrastructure of cells from the liver-endocrine pancreas system in hibernating animals].

In hibernated ground squirrel (Citellus erythrogenys) during various periods of hibernation morphological changes in organs participating in insurance of energoplastic homeostasis (liver, endocrine part of the pancreas) have been followed. At the beginning of hibernation certain signs of functional strain in the liver are observed-shortening and swelling of the endoplasmic reticulum (ER) canaliculi, decreases of glycogen resources and activation of the lysosomal apparatus, as well as certain features demonstrating its decreased activity--shortening cisterns in the Golgi complex, poorly manifested granular ER, tightening of mitochondrial matrix. At a deep hibernation, the signs of strain disappear, ultrastructure of hepatocytes corresponds to a new lower level of functioning in comparison to that in the active state and at the beginning of hibernation. During these periods the structure of endocrine cells in the pancreas demonstrates certain changes in the character of functioning of the cells. Ultrastructural transformations in the liver and endocrine part of the pancreas in the ground squirrel are mutually correlated.

Animals↗
PubMed1978

Ultrastruct of the hypothalamic neurosecretory nuclei of the dormouse (Eliomys quercinus L.) in the awakening and hibernating states.

The ultrastructure of the chief neurosecretory nuclei, supraoptic, (SON), parventricular, (PVN) and infundibular (IN), of the dormouse (Eliomys quercinus L.) has been studied during active and hibernating states. In the active state all three nuclei contained light, dark and intermediate type neurons. In hibernation the SON showed only a single light type which differed from the light neurons of the active state; the endoplasmic reticulum was vacuolized and sometimes grouped in 'honey-comb' structures; the cytoplasm contained accumulations of filamentous 'crystalline' material. None of these features occurred in the active state neurons. In the PVN and IN during hibernation both a light and a dark type neuron were present. 'Honey-comb' structures were seen in neurons of the PVN during hibernation, but never in those of the IN. Thus specific morphological features in the SON and PVN appear to be associated with the physiological changes of hibernation.

Animals↗
PubMed1995

Quantitative and qualitative aspects of the hibernation-related reduction of morphine physical dependence in the ground squirrel (Citellus lateralis).

The development of morphine physical dependence in the contrasting brain states of the nonhibernating (NH) vs. the hibernating (H) condition was measured in the ground squirrel hibernator Citellus lateralis. Morphine was infused continuously into the lateral ventricle (3.44, 6.88 and 13.75 micrograms/hr for periods of 1, 3 and 6 days) in NH and H animals, followed by measurement of the naloxone (1 mg/kg s.c.) evoked abstinence syndrome during the NH state (i.e., H animals were tested after arousal to the NH state). The results showed that morphine treatment during the NH state resulted in significant naloxone-evoked abstinence and an overall dose- and duration-related increase in the strength of the abstinence syndrome. By contrast, morphine treatment during hibernation resulted in significantly reduced abstinence compared with that observed after treatment during the NH state, with no significant morphine dose-response or duration-response trends evident. However, H-state morphine treatment did produce a dose-related reduction of hibernation bout duration. The reduction in the strength of dependence during the H state was associated with a qualitative change in the abstinence syndrome, as revealed by exploratory factor analysis. This change was reflected by an approximate reversal of the rank order of abstinence signs. These results demonstrate that hibernation-related changes in central nervous system function significantly reduce the liability for and change the character of the development of morphine dependence.

Animals↗
PubMedDate not supplied

[Blood plasma protein metabolism in ground squirrels in various stages of hibernation].

Synthesis intensity and a spectrum of synthetized proteins of blood plasma in the gophers at different hibernation stages (hibernation, awakening, being awake) were studied. It is established that the organism of hibernating animals has a constant concentration of plasma proteins during the whole period of the winter hibernation. Selective activation of synthesis of certain groups of plasma proteins is observed at different stages of hibernation in gophers and certain amount of specific proteins appear.

Animals↗
PubMed1994

Cytochemical and immunocytochemical characterization of nuclear bodies during hibernation.

Brown adipose tissue and liver of hibernating, arousing and euthermic individuals of the dormouse Muscardinus avellanarius were studies using ultrastructural cytochemistry and immunocytochemistry with the aim to investigate possible fine structural modifications of the cell nucleus during the seasonal cycle. The general morphology of brown adipocyte and hepatocyte nuclei was similar in the three experimental groups. However, three nuclear structural constituents were identified only in hibernating individuals: coiled bodies (CBs) and amorphous bodies (ABs) were observed in hepatocytes and, together with bundles of nucleoplasmic fibrils (NF), were present in brown adipocytes of hibernating dormice. In arousing animals only some structural constituents suggestive of poorly structured CBs were found. The latter showed the same immunocytochemical features as CBs of hibernating individuals, suggesting that they are disappearing CBs. A possible involvement of CBs in storing and/or processing RNA which must be rapidly and abundantly released upon arousal is discussed. ABs similarly to CBs contain RNA and nucleoplasmic ribonucleoproteins (RNPs) and could also be involved in mRNA pathways. NF do not contain nucleic acids or RNPs and seem to be composed of protein-aceous material; their functional role in the nuclear metabolism of hibernating brown adipocytes remains unclear.

Adipocytes↗
PubMed1993

Effects of opioid receptors antagonists administration to suprachiasmatic nucleus on hibernation of ground squirrels Citellus dauricus.

1. Drugs were administered to a suprachiasmatic nucleus through a chronically implanted cannula at the second day of a torpor bout of hibernating ground squirrels. After naltrexone injection, the body temperature of the hibernating animals increased and they aroused from hibernation within 20 hr after the injection. 2. Further experiments show that intra-suprachiasmatic nucleus perfusion of 1 nmol of ICI 174864 or nor-BNI, not beta-FNA, were able to increase the body temperature of hibernating ground squirrels and aroused them from hibernation within 20 hr after the injection.

Animals↗
PubMed1998

The extracellular matrix in hibernating myocardium--a significant factor causing structural defects and cardiac dysfunction.

Recently, we described chronic intracellular degeneration accompanied by fibrosis as typical structural features of hibernating myocardium and we concluded that cellular degeneration as a sign of the incomplete adaptation to the reduced blood flow is characteristic of hibernation. This study has been extended by analyzing the composition of the extracellular matrix proteins of the diseased myocardium. Areas of hibernating myocardium were identified in 38 patients by angiography, multigated radionuclide ventriculography, thallium scintigraphy with reinjection and low-dose dobutamine echocardiography. These areas were biopsied at cardiac surgery and were studied by electron microscopic and immunofluorescence techniques. Electron microscopy showed an enlarged extracellular space containing numerous particles of cellular debris, macrophages, fibroblasts, homogeneous matrix material and collagen fibrils. The basement membrane of the cardiomyocytes was thickened by an augmentation of laminin, fibronectin and collagen VI, but these proteins also were present in the matrix itself. Collagen fibrils were numerous and macrophages (CD68) and fibroblasts (vimentin) were increased. In situ hybridization showed an increase in mRNA for laminin, fibronectin and collagen. This observation is consistent with the conclusion that fibrotic scar formation was occurring continuously. It is postulated that fibrosis is the consequence of myocyte loss due to chronic underperfusion in the hibernating tissue. This will further injure myocytes so that a vicious cycle is established that leads to progressive loss of structural integrity and functional capacity. Since these changes are progressive, revascularization should be performed at the earliest time point possible in patients with areas of hibernating myocardium.

Aged↗
PubMed1991

Identification of ischemic and hibernating myocardium: feasibility of post-exercise F-18 deoxyglucose positron emission tomography.

The identification of ischemic and hibernating myocardium facilitates the selection of patients most likely to benefit from revascularization. This study examined the feasibility of metabolic imaging, using post-exercise F-18 deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of both ischemia and hibernation in 27 patients with known coronary anatomy. Normal post-exercise FDG uptake was defined in each patient by reference to normal resting perfusion and normal coronary supply. Abnormal elevation of FDG (ischemia or hibernation) was compared in 13 myocardial segments in each patient, with the results of dipyridamole stress perfusion imaging performed by rubidium-82 positron emission tomography (Rb-PET). Myocardial ischemia was diagnosed by either FDG-PET or Rb-PET in 34 segments subtended by significant local coronary stenoses. Increased FDG uptake was present in 32/34 (94%) and a reversible perfusion defect was identified by Rb-PET in 22/34 (65%, p less than .01). In 3 patients, ischemia was identified by metabolic imaging alone. In 16 patients with previous myocardial infarction, perfusion defects were present at rest in 89 regions, 30 of which (34%) demonstrated increased FDG uptake, consistent with the presence of hibernation. Increased post-exercise FDG uptake appears to be a sensitive indicator of ischemia and myocardial hibernation. This test may be useful in selecting post-infarction patients for revascularization.

Coronary Disease↗
PubMed1991

The stunned and hibernating myocardium: a brief review.

DEFINITIONS: Stunned myocardium is viable myocardium salvaged by coronary reperfusion that exhibits prolonged postischemic dysfunction after reperfusion. Hibernating myocardium is ischemic myocardium supplied by a narrowed coronary artery in which ischemic cells remain viable but contraction is chronically depressed. CLINICAL EVIDENCE: Stunned myocardium has been identified in the following patient groups: (1) thrombolysis or percutaneous transluminal coronary angiography (PTCA) in patients with acute evolving infarction; (2) unstable angina; (3) exercise-induced angina; (4) coronary artery spasm; (5) platelet aggregation or transient thrombosis of a coronary artery; (6) PTCA for chronic myocardial ischemia; and (7) immediately following coronary artery bypass graft (CABG). Evidence of hibernating myocardium (LV dysfunction) is found in the patient with severe coronary artery stenosis, even in asymptomatic patients at rest. Stunned myocardium returns to normal after a prolonged period of time (hours to weeks). Hibernating myocardium returns to normal function rather quickly if the cause is removed. DIFFERENTIATION: Stunned myocardium can be differentiated from hibernating myocardium by three clinical parameters, namely, LV wall motion, myocardial perfusion, and myocardial metabolism. Stunned myocardium has abnormal wall motion that tends to normalize in response to inotropes and postextrasystolic potentiation. Perfusion is adequate and metabolism is also adequate. Hibernating myocardium also has abnormal wall motion, which normalizes after nitrates, inotropes, post extrasystolic potentiation (PESP), PTCA, or CABG. Myocardial perfusion is reduced but can be reversed with PTCA or CABG and metabolism is adequate.

Animals↗
PubMed1996

Nuclear lamin expression in chronic hibernating myocardium in man.

Cardiomyocytes of chronic hibernating myocardium are known to undergo structural changes, indicative of dedifferentiation. Amongst these are changes in nuclear shape and chromatin distribution. Nuclear A-type lamins are known to be expressed in a differentiation-related fashion and to contribute to nuclear integrity and chromatin organization. Lamin expression was investigated with immunocytochemical staining procedures in biopsies from patients with chronic hibernating myocardium. The expression of A-type (lamin A and C) were shown to be downregulated during hibernation, while lamin B2 remained present in hibernating cardiomyocytes in a way similar to embryonic muscle cells. All heart muscle cells were shown to be negative for lamin B1. The absence of A-type lamins in chronic hibernating cardiomyocytes could be taken as an additional argument for the dedifferentiation state of these cells. The absence of A-type lamins was accompanied by dispersion of the nuclear heterochromatin, in a way similar to nuclei of embryonic cardiomyocytes.

Biopsy↗
PubMed2002

Basic fibroblast growth factor is upregulated in hibernating myocardium.

BACKGROUND: Ischemia is known to be a potent stimulus for the upregulation of angiogenic growth factors, such as basic fibroblast growth factor (bFGF). While previous investigations have shown that many angiogenic growth factors are upregulated in animal models of myocardial ischemia, the models used are limited in their ability to produce stable ischemia beyond a few weeks. Our laboratory uses a stable model of hibernating myocardium where later time points may be examined. Therefore, the goal of this study was to examine bFGF protein levels in the myocardium at baseline and 3 or 6 months following the onset of myocardial ischemia. METHODS: A total of 18 miniswine were studied. Basal endogenous levels of bFGF were measured in control animals (n = 6) immediately following sacrifice, while 12 other pigs underwent a 90% left circumflex artery occlusion with documented hibernating myocardium by positron emission tomography ((13)N-ammonia) and dobutamine stress echocardiography. These animals were studied at 3 (n = 7) and 6 months (n = 5) postoperatively. At sacrifice, six 3 x 3 mm samples were harvested from the left circumflex (hibernating) myocardium. Basic FGF levels (picograms per microgram of protein) were determined using ELISA kits. RESULTS: Basic FGF protein levels 3 months after the creation of hibernating myocardium were three times greater than in nonischemic control animals (P < 0.05), while levels at 6 months were increased sixfold compared to control animals (P < 0.05 versus both control and 3-month groups). CONCLUSIONS: Endogenous bFGF production is upregulated at 3 and 6 months in hibernating porcine myocardium. The angiogenic effects of exogenous bFGF delivered into ischemic myocardium with varying levels of endogenous growth factors must be determined.

Animals↗
PubMed1998

[Short-term hibernating myocardium: circulation, function and metabolism in sustained regional myocardial ischemia].

During moderate prolonged myocardial ischemia, the myocardium is dysfuctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow, i.e., a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns to control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". "Short-term hibernating" myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. A role for endogenous adenosine in the development of hibernation has been excluded, since neither contractile function, metabolic parameters, nor viability are altered by increased catabolism of endogenous adenosine by infusion of adenosine deaminase. Also activation of ATP-dependent potassium channels is not responsible for "short-term hibernation". "Short-term hibernating" myocardium has, however, reduced calcium responsiveness.

Animals↗
PubMed1995

Identification of hibernating myocardium by dobutamine stress echocardiography: comparison with thallium-201 reinjection imaging.

The aim of this study was to determine the diagnostic value of dobutamine stress echocardiography (DSE) in the identification of hibernating myocardium and to compare its predictive accuracy with that of thallium-201 reinjection (RI) imaging. The subjects were 26 patients with wall motion abnormalities related to stenosed coronary arteries. DSE predicted postrevascularization improvement in 31 of 33 segments that were considered to be hibernating and identified 8 of 10 nonhibernating segments. In contrast, thallium-201 scintigraphy predicted all 33 hibernating segments when a post-RI myocardial thallium uptake in ischemic areas of > or = 50% of the maximum count in normal segments was used as a positive marker of myocardial viability. However, thallium studies predicted only 30 of 33 hibernating segments when thallium redistribution (RD) was used as a marker of viability in delayed or RI images. Among the 10 nonhibernating segments, an uptake of < 50% was observed in 4 segments and negative thallium-201 RD was observed in 5 segments. The sensitivity, specificity, and predictive values (PV) of DSE were 94%, 80%, positive PV 94%, and negative PV 80%, respectively. In contrast, the sensitivity, specificity, and PV of thallium-201 RI imaging were 100%, 40%, 85%, and 100% with uptake > or = 50% and 91%, 50% 86%, and 63% with RD, respectively. These results suggest that DSE may be useful for identifying hibernating myocardium and could therefore be helpful in selecting candidates for coronary revascularization.

Adult↗
PubMed1995

Assessment of hibernating myocardium by dobutamine stimulation in a canine model.

OBJECTIVES: The purpose of this study was to 1) develop an animal model of hibernating myocardium, and 2) evaluate the ability of dobutamine stimulation to detect hibernating myocardium using both qualitative and quantitative assessment of regional myocardial function. BACKGROUND: Left ventricular dysfunction may be due to chronic ischemia with or without myocardial infarction and may improve after coronary blood flow is enhanced by revascularization procedures. This condition has been coined "hibernating myocardium" and variably defined in recent years. The results of recent clinical studies suggest that dobutamine echocardiography may be useful for detecting viable myocardium in patients with left ventricular dysfunction. METHODS: Twenty-one dogs underwent initial operation. Sonomicrometer crystals were implanted, and baseline measurements of segment shortening and wall thickening (by echocardiography) were made. A coronary artery was ligated; the chest was closed; and measurements were repeated. Dobutamine was incrementally infused with determination of wall thickening and segment shortening at baseline and on days 3 and 7 and weeks 2 and 4 after coronary artery occlusion. Finally, the chest was reopened; the ligated vessel was bypassed; and measurements were repeated. RESULTS: Of the 10 dogs that completed the entire protocol, 7 had varying degrees of nontransmural myocardial infarction (group 1), and 3 had complete transmural myocardial infarction (group 2). In group 1, baseline function was significantly impaired compared with preligation function but increased during dobutamine infusion. When reperfused after 4 weeks, both wall thickening and segment shortening increased significantly. In group 2, significant changes were not seen during the dobutamine studies or after reperfusion. Myocardial perfusion during dobutamine infusion increased in group 1 but did not change in group 2. CONCLUSIONS: We demonstrated improvement in chronically dysfunctional myocardium after restoration of previously interrupted myocardial blood flow in dogs after nontransmural myocardial infarction, thus validating a canine model of hibernating myocardium. As assessed by two independent methods, dobutamine infusion identified hibernating myocardium in an animal model.

Animals↗
PubMed2005

Characterization of hibernating myocardium with NOGA electroanatomic endocardial mapping.

Because the terms "hibernation" and "viability" are not interchangeable, the recognition of hibernating myocardium within viable segments remained elusive for NOGA electroanatomic endocardial mapping. The aim of the present study was to determine the characteristics of hibernating myocardium in NOGA mapping. Baseline and follow-up endocardial mapping, thallium-201 myocardial perfusion scintigraphy at rest, and contrast ventriculography were performed in 28 patients who had proved viable myocardium before and 7.3 +/- 2.5 months after percutaneous coronary intervention. Significantly improved regional wall motion in the revascularized territory (region of interest) was confirmed in 9 patients (group 1) at follow-up (from -2.11 +/- 0.87 to -1.48 +/- 0.43 SD/chord, p <0.05), whereas no change in regional wall motion was observed in 19 patients (group 2; from -2.56 +/- 0.88 to -2.79 +/- 0.91 SD/chord). Average normalized thallium uptake at rest increased significantly in groups 1 and 2 after revascularization. A trend toward increased unipolar voltages in the region of interest was observed in group 1 at follow-up (from 10.6 +/- 3.5 to 11.7 +/- 4.0 mV, p = 0.073), whereas no change was observed in group 2 (from 8.7 +/- 4.4 to 8.9 +/- 3.8 mV). A significant increase in local linear shortening was measured only in group 1 (from 7.5 +/- 5.2% to 10.3 +/- 3.9%, p <0.05). Hibernating myocardial segments exhibited significantly higher unipolar voltages and late thallium uptake at rest at baseline. Receiver-operator characteristic analysis showed a mean unipolar voltage of 9.0 mV (predictive accuracy 0.708, common sensitivity and specificity 72%) in the region of interest for prediction of functional recovery. In conclusion, for characterizing the hibernating myocardium within viable segments, NOGA endocardial mapping offers on-line guidance for percutaneous coronary and noncoronary myocardial revascularization.

Aged↗
PubMed2000

The biology of myocardial hibernation.

Patients with chronic coronary artery disease frequently have contractile dysfunction that recovers upon reperfusion. The concept of myocardial hibernation views the observed reduction in contractile function not as the result of an ongoing energetic deficit, but as an adaptive down-regulation that serves to maintain myocardial integrity and viability. In the experiment, sustained perfusion-contraction matching, recovery of energy and substrate metabolism during ongoing ischemia, the potential for recruitment of inotropic reserve, lack of necrosis, and therefore recovery of function upon reperfusion are established features of hibernation. Apart from reduced calcium responsiveness, the underlying mechanisms are still unclear. In patients, the importance of reduced baseline blood flow vs. that of superimposed repetitive stunning is somewhat controversial; however, in most studies blood flow is reduced, and the myocardium must be ischemic often enough to have persistent dysfunction. Morphologically, hibernating myocardium displays features of dedifferentiation, with loss of cardiomyocytes and myofibrils, and of degeneration, with increased interstitial fibrosis. Patients with hibernating myocardium must be identified and undergo revascularization. With a better understanding of the underlying mechanisms of hibernation, these adaptive responses to ischemia can potentially be recruited and reinforced pharmacologically to delay impending myocardial infarction.

Calcium↗
PubMedDate not supplied

Influence of the assessment of defect severity and intravenous nitrate administration during tracer injection on the detection of viable hibernating myocardium with data-based quantitative technetium 99m-labeled sestamibi single-photon emission computed tomography.

BACKGROUND: This study aimed to verify whether the assessment of defect severity and the infusion of nitrates during tracer injection improve the capability of data-based 99mTc-labeled sestamibi single-photon emission computed tomography (SPECT) to recognize hibernating myocardium. METHODS AND RESULTS: Of 66 asynergic coronary territories in 40 patients with left ventricular dysfunction, 28 had postrevascularization functional recovery (hibernating) and 38 had unchanged dysfunction (fibrotic). Defect severity was lower in the hibernating than in the fibrotic territories on both baseline (p < 0.01) and nitrate SPECT (p < 0.002). Nitrate was superior to baseline SPECT to differentiate the hibernating from the fibrotic territories (sensitivity 96% vs 75%, p < 0.05; receiver-operating characteristic curve area 0.75 vs 0.63, p < 0.001) and to identify the patients with improved left ventricular ejection fraction (receiver-operating characteristic curve area 0.68 vs 0.58; p < 0.05). CONCLUSIONS: The analysis of defect severity in combination with nitrate infusion clearly improves the value of 99mTc-labeled sestamibi SPECT for the recognition of hibernating myocardium and the prediction of postrevascularization recovery.

Adult↗