DigitalUM :: Browsing by Subject "Ischemia"

Browsing by Subject "Ischemia"

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Open Access
Alternate approach to understanding the molecular mechanisms of stroke-induced injury
(Murcia : F. Hernández, 2007) Willing, A.E.; Pennypacker, K.
Research in the area of stroke has not yielded any new treatments, besides tissue plasminogen activator. New findings are suggesting that the therapeutic window of providing neuroprotection is wider than once thought. Moreover, the role of the peripheral immune system in abetting neurodegeneration is being elucidated, but it appears this reaction occurs 2- 3 days after the stroke. This mini-review examines this new evidence about the molecular mechanisms leading to stroke-induced neuronal death, which suggests new therapeutic approaches to its treatment.
Open Access
Atrophic hepatocytes express keratin 7 in ischemia-associated liver lesions
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Delladetsima, Ioanna; Sakellariou, Stratigoula; Kokkori, Aikaterini; Tiniakos, Dina
Aim: To investigate atrophic parenchymal changes in ischemic liver conditions. Design: We studied 18 cases of hepatic lesions with atrophic changes due to altered blood flow (hepatic venous congestion n=15 including 4 cases with additional nodular regenerative hyperplasia-NRH, NRH n=1, and antiphospholipid syndrome with patchy parenchymal atrophy n=2). Metaplastic hepatocellular changes, hepatocyte proliferation, hepatic stellate cell (HSC) activation, and sinusoidal capillarization were examined immunohistochemically with antibodies to keratins (K) 7 and 19, Ki67, αSMA and CD34, respectively. Results: K7 was positive and K19 was negative in zone 3 atrophic hepatocytes in venous congestion and in areas of plate atrophy, as well as in congested or compressed sites in NRH. Sinusoidal CD34-positivity indicating capillarization accompanied K7 immunoexpression. Masson trichrome revealed sinusoidal fibrosis to be restricted in atrophic areas, usually mild and in 7 cases focally dense. αSMA expression expanded beyond K7- positive areas. Ki67 was negative in K7-positive hepatocytes. Conclusion: Ischemic parenchymal changes are characterized by hepatocyte K7 immunoexpression, sinusoidal capillarization, HSC activation and lack of cellular proliferation, indicating an early reaction of the major liver parenchyma cellular components creating a more resistant microenvironment. These phenotypic alterations may prove valuable in the discrimination of ischemic liver lesions.
Open Access
Cardiac ischemia and reperfusion in spontaneously diabetic rats with and without application of EGb 761, I. cardiomyocytes
(Murcia : F. Hernández, 2008) Schneider, Rick; Welt, Klaus; Aust, Wolfram; Löster, Heinz; Fitzl, Günther
Diabetic cardiomyopathy is known to result in increased mortality after ischemic events. Permanently increased oxidative stress with formation of oxygen-free radicals plays a key role in the development of specific heart muscle disease. Associated lesions include structural alterations to cardiomyocytes. Antioxidative treatment in addition to the usual insulin substitution would seem sensible in preventing or delaying long-term diabetic complications and protecting the myocardium against acute ischemic events. We investigated the effects of radical scavenger Ginkgo biloba extract EGb 761 against diabetes-induced damage to cardiomyocytes and additional ischemia/ reperfusion injury in spontaneously diabetic BioBreeding/Ottawa Karlsburg (BB/OK) rats, as a model of diabetic myocardium infarction. Morphological and morphometric parameters of heart muscles were analyzed by light and electron-microscopic techniques. We used immunohistochemistry to evaluate parameters of oxidative stress (superoxide dismutase [SOD]) and inducible nitric oxide synthase (iNOS) protein expression. Our results indicated that A) Diabetic myocardium appears more vulnerable to ischemia/ reperfusion damage concerning ultrastructure of cardiomyocytes (sarcomeres, vacuoles, mitochondria), expression of antioxidative enzymes (CuZnSOD, MnSOD), and iNOS than normal myocardium; B) Pretreatment of diabetic myocardium with EGb and additional ischemia/reperfusion leads to a relative improvement in myocardial ultrastructure compared to unprotected myocardium. In summary, EGb appears to be promising as an adjuvant therapeutic drug in diabetics with respect to ischemic myocardium injury. It may contribute to the prevention of late diabetic complications in diabetic cardiomyopathy.
Open Access
Cardiac ischemia and reperfusion in spontaneously diabetic rats with and without application of EGb 761: II. Interstitium and microvasculature
(Murcia : F. Hernández, 2009) Schneider, Rick; Welt, Klaus; Aust, Wolfram; Löster, Heinz; Fitzl, Günther
Besides alterations in cardiomyocytes themselves, diabetic cardiopathy is characterized by interstitial and microvascular disorders. On the assumption that a specific heart muscle disease develops due to permanently increased oxidative stress on liberation of oxygen-free radicals, adjuvant application of antioxidative therapeutics appears promising in preventing or delaying long-term diabetic complications and protecting the myocardium against acute ischemia. We have investigated the effects of Ginkgo biloba extract (EGb 761), a radical scavenger, against diabetesinduced myocardial interstitium and microvasculature damage, and against additional ischemia/reperfusion injury in spontaneously diabetic BioBreeding/Ottawa Karlsburg (BB/OK) rats modelling diabetic cardiac infarction. Morphological and morphometric parameters in the heart muscle were evaluated by light and electron microscope. We used immunohistochemistry to investigate collagen protein expression as a marker for tissue remodelling together with endothelial nitric oxide synthase (eNOS) protein expression as a marker for endothelial-dependent vasodilation. We also evaluated inflammation response caused by neuropeptide Substance P and interacting mast cells in the diabetic heart. Our results revealed that A) Diabetic myocardium appears more vulnerable to ischemia/reperfusion injury than normal myocardium with regard to myocardial interstitium and microvessel ultrastructure, as well as eNOS protein expression; B) Inflammation response increases in diabetic animals exposed to ischemia/reperfusion injury compared to controls; C) Pre-treatment of diabetic myocardium with EGb results in an improvement of impaired endothelial-dependent vasodilation in diabetes and additional ischemia/ reperfusion, diminished mast cell and substance P accumulation, and better preserved myocardial ultrastructure compared to unprotected myocardium. In conclusion, EGb may act as a potent therapeutic adjuvant in diabetics with respect to ischemic myocardial injury, and may contribute to preventing late complications in diabetic cardiopathy.
Open Access
Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia
(Murcia : F. Hernández, 1997) Babál, P.; Pecháñová, O.; Bernátwá, I.; Stvrtina, S.
Pathophysiological effects of nitric oxide (NO)-deficient hypertension are much better known than are the potential morphological changes. Hearts and main arteries were studied in 15 week old male Wistar rats administered N~-nitro-L-arginine methyl ester (L NAME) for 4 weeks. A dose of 40 mgkgíday increased systolic arterial pressure by 30%, while heart rate decreased by 20%. Heartlbody weight ratios were not significantly changed. Total cardiac RNA and DNA content and [14c]leucine incorporation into myocardial protein were, however, increased by 15%, 228% and 97%, respectively. Light microscopy of hearts showed subendocardial areas of necrosis along with different stages of healing. Morphometric evaluation demonstrated significant increase in myocardial fibrosis. Serum lactate dehydrogenase increased by 91%. Proliferation cell nuclear antigen (PCNA) immunohistochemistry indicated positive cells in areas of postischemic repair. Chronic inhibition of NO synthase (NOS) resulted in periarterial fibrosis and hyperplasia of the media in coronary arteries and aorta. RNA and DNA content, and [14c]leucine incorporation into protein of aorta increased by 255%, 95% and 49%, respectively. PCNA staining showed numerous positive nuclei in the media of coronary arteries and the aorta. It is concluded that inhibition of NOS leads to systemic hypertension with foca1 myocardial fibrosis reflecting reparative responses associated to ischemic injury. This sequence of alterations involves impaired arterial relaxation, and uncontrolled vascular media1 proliferation attributed to the absence of smooth muscle cell proliferation inhibition by NO.
Open Access
Chronic morpho-functional damage as a consequence of transient ischemia-reperfusion injury of the small bowel
(Murcia : F. Hernández, 2010) Morini, Sergio; Elias, Georg; Brown, Melisa; Subbotin, Vladimir; Rastellini, Cristiana; Cicalese, Luca
Introduction: The prevailing notion is thatischemia reperfusion injury of the small bowel inducestransient changes that resolve within a few days post-occurrence. However, chronic injury has been describedfollowing a single ischemia reperfusion in the kidney.We proceeded to ascertain if a similar outcome is alsowitnessed in the small bowel. Materials and methods:ACI rats (n=32) underwent 1, 2 or 3 episodes ofischemia reperfusion by clamping the superiormesenteric artery for 45 minutes at 7-day intervals.Control groups included sham-operated (n=6) or non-operated (n=5) rats. Morphology was examined at dayninety post-ischemia reperfusion and immunostainingwas used to evaluate macrophage infiltration,microvascular distribution, and apoptosis. RT-PCR wasused to evaluate expression of Inter-Cellular AdhesionMolecule-1 (ICAM-1), transforming growth factor-ß(TGF-ß), Insulin Growth Factor-I (IGF-1), and InsulinGrowth Factor-I Receptor (IGF-R). Intestinal functionwas evaluated by D-xylose performed 24 hours and 4, 8,and 12 weeks after reperfusion. Results: Chronicmorphologic changes were observed with degenerationof crypts, endothelial damage, matrix degeneration, andheightened lymphocyte degeneration within the Payer’spatches. Major structural changes were characterized byvillous atrophy from partial to total. The grade ofhistological injuries was significantly increased(P<0.001) after multiple ischemia reperfusion episodes.A higher number of apoptotic cells (P<0.001) and aprominent macrophage infiltration (P<0.05) was alsowitnessed. Altered expression of ICAM-1, TGF-ß, andIGF-1 was observed. At 24 hours after ischemiareperfusion D-xylose absorption was diminished,returning to baseline values within 4 weeks and becoming abnormal again at 8 and 12 weeks (P<0.05).CONCLUSIONS: Unlike the prevailing conviction,these data demonstrate that transient ischemiareperfusion repeated injuries of the small bowel result inchronic intestinal damage.
Open Access
De novo expression of the hemoglobin scavenger receptor CD163 by activated microglia is not associated with hemorrhages in human brain lesions
(Editores F. Hernandez y Juan F. Madrid. Murcia, Universidad de Murcia, Departamento de Biologia Celular e Histologia, 2011) Holfelder, K.; Schittenhelm, J.; Trautmann, K.; Haybaeck, J.; Meyermann, R.; Beschorner, R.
The main function of CD163 (hemoglobin scavenger receptor) is to bind the hemoglobinhaptoglobin complex, thereby mediating extravasal hemolysis. However, CD163 also has an antiinflammatory function. After CD163-mediated endocytosis, hemoglobin is catabolized further by hemeoxygenase 1 (HO-1). Previously, we found expression of HO-1 to be restricted to microglia/ macrophages at sites of hemorrhages in human traumatic and ischemic brain lesions. We now investigated if CD163 expression is also correlated with hemorrhages in brain lesions. Methods. Autopsy brain tissue from 44 cases with hemorrhagic brain lesions (32 traumatic brain injuries/TBI, 12 intracerebral bleedings/ICB), 56 nonhemorrhagic brain lesions (30 ischemias, 26 hypoxias) and 6 control brains were investigated. The post injury survival times ranged from a few minutes to 60 months. Results. In controls, single perivascular monocytes expressed CD163, but only single CD163+ microglia were found in 3/6 cases. CD163+ cells in the parenchyma (activated microglia/macrophages) increased significantly within 24 hours after trauma and ischemia and within 1-7 days following ICB or hypoxia. Overall, significantly lower and higher levels of parenchymal CD163+ cells occurred in hypoxia and ischemia, respectively. Perivascular CD163+ cells also increased significantly in all pathological conditions. In areas remote from circumscribed brain lesions (TBI, ICB, ischemia), significant changes were only found in ICB and ischemia. Conclusions. De novo expression of CD163 by activated microglia/macrophages and CD163+ infiltrating monocytes are neither restricted to nor predominant in hemorrhagic brain lesions. Thus, the antiinflammatory function of CD163 probably predominates, both in hemorrhagic and non-hemorrhagic brain lesions and points to possible immunomodulatory treatment strategies targeting CD163
Open Access
Experimental study of WGA binding on the endothelial cell surface in cerebral ischemia
(Murcia : F. Hernández, 1986) Shozo Nishida; Fumiharu Akai; Shingo Hiruma; Mitsuyo Maeda; Kurenai Tanji; Shigeo Hashimoto
The relationship between the saccharide chain on the endothelial cell surface and the permeability of intracerebral blood vessels has been studied. In the present study, wheat germ agglutinin (WGA) was perfused into capillaries in the area postrema of the normal Mongolian gerbil, where the blood brain barrier (BBB) is known to lack, and into intracerebral blood vessels, the BBB of which had been destroyed by experimentally induced brain ischemia. The light microscopic features of the sections from WGA-perfused brain tissues of the normal gerbil revealed that most of the blood vessels, including capillaries in the brain parenchyma, showed positive findings (the reaction induced a very distinct staining of the vascular wall) from which the course and structure of the fine vessels could be determined. The reaction to WGA on the diaphragma fenestra (DF) in capillaries in the area postrema was relatively weak, and DF without the reaction were occasionally revealed by electron microscopy. The gerbil, in which cerebral ischemia had been induced, also showed partial defect of the reaction with WGA on the lumina1 side of the endothelial cells. The results of the present experiment suggest some degree of correlation between the saccharide chains, including the specific monosaccharide of WGA, on the endothelial cell surface and permeability. It was considered that lectin can be used as an index for morphological observations, suggesting an alteration in function of the endothelial cell membrane. In addition, the perfusion method in this experiment suggested the possibility of distinguishing pinocytotic vesicles from pits of cell membranes.
Open Access
Exploring ischemia-induced vascular lesions and potential pharmacological intervention strategies
(Murcia : F. Hernández, 2005) Aliev, G.; Obrenovich, M.E.; Seyidova, D.; De la Torre, J.C.
Structural changes in vessels under the influence of ischemia play an important role in the pathogenesis of many diseases, most important of which are stroke and myocardial infarction or myocardial insult. Over the years, information has been gathered, which implicate a role for ischemic vascular changes in the pathogenesis of crush-syndrome, atherosclerosis and other vascular diseases. When blood vessels are damaged they become unresponsive to a stimulus, which normally elicits vasodilatation and can lead to intraluminal thrombosis and ischemic events. The aim of this review is to explore the structural changes seen in vessels affected by ischemia reperfusion injury. With ischemia, the development of observable changes to vascular structure is multifactorial. One key factor is reperfusion ischemic injury. Moreover, the duration of the ischemic event is an important factor when determining both the prognosis and the type of morphological change that is observable in affected vessel walls. In this regard, the deleterious progression of blood flow impairment and its severity depends on the specific organ involved and the type of tissue affected. Further, there are regional differences within affected tissues and the degree of microvascular injury is well correlated with differences in the nature and severity of the ischemic event. Any method aimed at preventing and treating ischemic reperfusion injuries in vessels, based on these investigations, should likewise be able to decrease the early signs of brain, cerebrovascular and heart injury and preserve normal cellular architecture.
Open Access
Histomorphometric analysis with a proposed tissue lesion index in ischemia-reperfusion induced gastric mucosa damage
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Peña Mercado, Eduardo; Garcia Lorenzana, Mario; Beltran, Nohra E.
Damage to the gastrointestinal mucosa caused by ischemia - reperfusion is a significant clinical problem associated with various physiopathological conditions. Our group has conducted various studies in patients in critical conditions and in animal models to identify early damage to the gastric mucosa under ischemia using impedance spectroscopy. It is important to perform a quantitative histopathological analysis which can be linked to changes in impedance of the gastric mucosa under conditions of ischemia and I/R. Aim. To propose a tissue lesion index which considers pathological alterations inherent to the inflammatory process and cell damage which may be directly related to changes in impedance under conditions of ischemia and I/R. Methods. The animals were randomly distributed into 4 groups: control, ischemia (30 min), and I/R (30 and 60 min). Qualitative histopathological analysis was performed; the vascular area, glandular lumen area, the number of damaged cells, and the depth of the erosion were also quantified to obtain a scale to propose a tissue lesion index (TLI). Results. Under ischemic conditions, histopathological analysis showed edema and necrosis in epithelial cells, and vascular congestion. In I/R (30 and 60 min) conditions, areas of epithelial erosion were generated. Damage was classified based on the TLI. A TLI threshold of 3 showed a predictive value of tissue lesion. Conclusion. The proposed gastric lesion index allows us to objectively quantify and classify damage to the gastric mucosa produced by I/R.
Open Access
Histopathological changes associated to an absorbable fibrin patch (Tachosil®) covering in an experimental model of high-risk colonic anastomoses
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) García Vásquez, C.; Gómez García de las Heras, S.; Pastor Idoate, C.; De Pablo, D.; Fernández Aceñero, M.J.
Background. TachoSil® is a fibrin sponge that contains fibrinogen and thrombin and is a useful adjuvant to enhance control of air leaks in thoracic surgery and to control bleeding in vascular and general surgery. Its use in intestinal surgery to prevent suture dehiscence is currently under investigation. Material and Methods. We report the results of a prospective randomized experimental study on 33 large white pigs in which a high-risk suture was created by induction of ischemia. We randomly employed TachoSil® to cover the anastomosis in half of the animals compared to a control group of uncovered anastomosis. After euthanasia, postmortem analysis was performed describing the findings related to anastomotic leakage, peritonitis and grade of adhesions. The entire anastomosis was resected in bloc and sent for histopathological analysis. A single blinded-pathologist evaluated the histopathological features of the specimens. Results. We found statistically significant differences favouring the patch in decreasing leakage in the covered group. The healing process did not show significant differences between groups, although a higher rate of microscopic abscess was observed in the covered group. Conclusion. The use of fibrin sealants covering highrisk intestinal sutures has a positive effect in avoiding macroscopic anastomotic leakage. The patch did not have any influence in the anastomotic healing process, however, as a result of the effect in containing the inflammatory response, it may increase the rate of abscess.
Open Access
Immunohistochemical change of actin in exprerimental myocardial ischemia. Its usefulness to detect very early myocardial damages
(Murcia : F. Hernández, 1987) Shozo Nishida; Shingo Hiruma; Shigeo Hashimoto
Pathomorphological diagnosis of acute myocardial infarction has many problems in human autopsy materials less than 4 to 6 hours after clinical onset and in rats 2 to 3 hours after experimental coronary occlusion. Since immunohistochemical reaction deuends - ~ on the antigei determinant site of the material, chañges in the reaction may reflect alterations at the molecular level in myocardial fibers. With this consideration in mind, the effectiveness of diagnosing infarction at the earliest (possible) stage, and the changes of actin filaments were investigated through experiments, using immunohistochemical methods involving anti-actin antibodies produced from chicken gizzards in our laboratory. The left coronary arteries of rats were ligated to produce ischemia. Dehydrogenases were shown to be still present by triphenyltetrazolium chloride (TTC) reaction, but the anti-actin antibody reaction had disappeared in areas corresponding to the ischemic sites. However, on electron microscopic examination of these sites, actin fibers were clearly revealed. In the case of ischemia lasting for more than 6 hours, the anti-actin antibody reaction had disappeared, corresponding to the disappearance of the TTC reaction. At this stage, myocardial actin fibers were revealed by electron microscopic examination. These results indicate that ischemia induces some type of biochemical degeneration at the molecular level of myocardial actin, most likely the change of actin polymerization. Moreover, they show that the anti-actin antibody technique is capable of detecting such very early degenerative and ischemic changes proving itself to be better suited for determining the range and degree of early infarction.
Open Access
Ischemic culture of dental pulp-derived cells is a useful model in which to investigate mechanisms of post-ischemic tissue recovery
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Agata, Hideki; Sumita, Yoshinori; Asahina, Izumi; Tojo, Arinobu; Kagami, Hideaki
Dental pulp is a soft tissue characterized by unique regenerative properties. It is located in the center of each tooth, and is surrounded by hard tissue (dentin). Vascular access is limited to a small foramen at the root apex. Because of this anatomical limitation, dental pulp can easily lose its blood supply, causing the tissue to become ischemic. This occurs, for example, when a tooth is dislocated by traumatic injury or is subjected to inflammation. Since ischemia is caused by a critical shortage of oxygen and nutrients, ischemic damage is usually irreversible, even when the ischemic event is transient. However, unlike ischemia-sensitive organs such as the brain and heart, dental pulp is relatively ischemia-resistant, and recovers from ischemic injury by regenerating damaged tissue. The mechanisms by which this regeneration occurs are poorly understood, but are being investigated in cell culture models that mimic in vivo ischemic conditions using a combination of hypoxia and nutrient deprivation. Here, we review the use of ischemic cell culture to investigate the mechanisms of post-ischemic dental pulp tissue recovery.
Open Access
Ischemic preconditioning: tolerance to hepatic ischemia-reperfusion injury
(Murcia : F. Hernández, 2004) Serafín, A.; Fernández-Zabalegui, L.; Prat, Narcis; Wu, Z.Y.; Roselló-Catafau, J.; Peralta, C.
Hepatic ischemia-reperfusion (I/R) injury still remains an unresolved problem in both liver resectional surgery and liver transplantation and may be responsible for liver failure, lung injury and death. The current review summarizes the findings reported to date on the effectiveness of ischemic preconditioning against liver and lung damage associated with hepatic I/R injury and the underlying protective mechanisms. The effect of ischemic preconditioning on the mechanisms potentially involved in hepatic I/R injury, including alterations in energy metabolism, neutrophil accumulation, microcirculatory disturbances, formation of proinflammatory mediators, such as endothelin and tumor necrosis factor-alpha, and reactive oxygen species generation have been evaluated. In this review, we address the role of preconditioning in the increased vulnerability of fatty livers to hepatic I/R injury. The effectiveness of ischemic preconditioning versus pharmacological strategies that could simulate the benefits of liver preconditioning has been also discussed.
Open Access
Ischemic stroke activates the VE-cadherin promoter and increases VE-cadherin expression in adult mice
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Nakano Doi, Akiko; Sakuma, Rika; Matsuyama, Tomoiro; Nakagomi, Takayuki
Endothelial cells (ECs) are a key component of the blood-brain barrier (BBB). Healthy ECs in the BBB form inter-endothelial junctions, including adherens junctions (AJs). Under pathological conditions, such as after ischemic stroke, the BBB may be functionally compromised. However, gene and protein expression patterns involving endothelial AJs have not been well studied. Because expression levels of endothelial AJs are considered to be related to BBB functionality, we investigated the expression pattern of a representative endothelial AJ marker, VE-cadherin, in healthy and diseased mice. We first examined the expression of VE-cadherin in developing mouse brains. In addition, using a mouse model of cerebral infarction, we investigated the expression pattern of VE-cadherin in pathologic brains. Furthermore, using the Cre-LoxP system, we established a strain of mice expressing yellow fluorescent protein (YFP) under the control of the VE-cadherin promoter and investigated the expression pattern of YFP-expressing ECs in developing and pathologic murine brains. VE-cadherin protein and YFP expression driven by the VE-cadherin promoter both showed that VE-cadherin expression was weak during embryonic stages, followed by a steady increase postnatally, which then decreased during adulthood. However, following ischemic stroke, imunohistochemistry of VE-cadherin demonstrated an upregulation in ECs within ischemic regions, concomitant with YFP upregulation. These findings reveal that ischemic stroke activates the VE-cadherin promoter and increases VE-cadherin protein expression, which suggests that endothelial VE-cadherin is involved in the reconstruction of the BBB following ischemic stroke.
Open Access
lmmunohistochemical reaction of myocardial fibers with actin antiserum in autopsy cases of myocardial infarction
(Murcia : F. Hernández, 1986) Shigeo Hashimoto; Shozo Nishida; Shingo Hiruma; Manabu Takahashi; Yoshiki Enomoto; Kuniyasu Sakatani
The purpose of this study was to determine the immunoreactivity of myocardial actin filaments with actin antiserum and to examine the significance of its application to diseased human cardiac muscle. The actin was extracted and purified from chicken gizzards. Anti-actin rabbit serum was prepared and purified by affinity chromatography and defined by an immunoblotting test. Using the avidin-biotin-peroxidase complex (ABC) method, the actin antiserum was applied to paraffin sections prepared from hearts taken from routine autopsies of patients who had died of myocardial infarction. Reactivity was shown to be completely lost, not only in necrotized fibers, but also in non-specific degenerative fibers which could be identified by their eosinophilic cytoplasm with pyknotic nuclei, and clearly remaining and/or diminished cross-striations stained with hematoxylin-eosin. In contrast, hypertrophic myocardial fibers adjacent to granulation or scar tissue and those adjacent to infarcted foci exhibited a more intense reaction. These results indicated that the immunohistochemical reaction of actin filaments can be used for the easy detection of very mild degrees of degeneration of cardial muscle fibers, and for hypertrophic fibers adjacent to diseased foci. Studies of the immunoreactivity of actin protein suggestive of alteration at the molecular level might yield morphological clues regarding the nature of functional activity in the contraction of cardiac fibers.
Open Access
Morphological abnormalities in the sural nerve from patients with peripheral vascular disease
(Murcia : F. Hernández, 1991) Rodríguez-Sánchez, C.; Medina sánchez, M.; Malik, Rayaz A.; Ah-See, A.K.; Sharma, A.K.
The present paper has been written in order to determine the morphological alterations in the sural nerve from patients with chronic arteriosclerotic occlusive disease. Eight patients with Peripheral Vascular Disease (PVD) and six age-matched control subjects were studied. Morphometric data revealed two groups of patients, one of them with mild disease (n=5), and the other one with severe damage (n=3,) consisting in loss of myelinated fibres and increase in the number of small fibres (p < 0.005). Teased nerve fibres and electron microscopic studies also showed two types of patients, with respect to the myelin or the axonal alterations. The unmyelinated fibre population was affected equally in both groups. In conclusion, this study supports the idea that ischemia is able to cause structural alterations in the peripheral nerve, and that it can play a role in the development of neuropathy.
Open Access
Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration
(Murcia: F. Hernández, 2010) Heissig, Beate; Nishida, Chiemi; Tashiro, Yoshihiko; Sato, Yayoi; Ishihara, Makoto; Ohki, Makiko; Gritli, Ismael; Rosenkvist, Jeanette; Hattori, Koichi
Ischemic tissue regeneration depends on neovascularization, the growth of new blood vessels. Bone marrow (BM)-derived cells, including neutrophils, have been shown to contribute to neovascularization during hind limb ischemia and inflammation. Neutrophils produce a broad array of angiogenic growth factors and proteases, which promote remodeling of arterioles into arteries through proteolytic mechanisms. Matrix metalloproteinases (MMPs) have been shown to play a role in the recruitment of neutrophils to sites of inflammation, which requires the extravascular migration of neutrophils through the extracellular matrix. Neutrophils control critical steps during angiogenesis and neutrophil-derived MMPs can promote neoangiogenesis, and collateral growth and perfusion recovery, in part by liberating vital angiogenic growth factors, including vascular endothelial growth factor-A (VEGF-A). This review focuses on the role of neutrophils as key players in the control of the angiogenic process during ischemic tissue regeneration. Aspects of neutrophil regulation, in particular regulation by its major growth factor granulocyte colonystimulating factor (G-CSF), the role of the unique, readily available, neutrophil-derived MMP-9, and the functional consequences of this MMP-9 activation for angiogenesis, such as MMP-mediated release of biologically relevant cytokines from the matrix and cell surfaces, will be discussed.
Open Access
Spatio-temporal expression patterns of microRNAs in remodelling and repair of the infarcted heart
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Chiarella-Redfern, H.H.; Rayner, K.J.; Suuronen, E.J.
MicroRNAs (miRNAs) are small, nonmessenger RNAs, 20-22 nucleotides in size, which regulate gene expression at the post-transcriptional level. Typically, miRNAs target the 3’ untranslated region (3'UTR) of mRNA transcripts leading to mRNA degradation or translational repression. The known dysregulation of miRNAs during cardiac ischemia and the crucial role of miRNA-dependent regulation of angiogenesis, fibrosis and hypertrophy present interesting therapeutic opportunities for repairing and regenerating the heart after myocardial infarction (MI). An understanding of the expression pattern and localization of deleterious and beneficial miRNAs during cardiac ischemia is necessary for the development of therapeutics designed to specifically treat the affected tissue and cell populations. This review focuses on the role and localization of key miRNAs implicated in MI while highlighting how their manipulation may promote cardiac repair.
Open Access
The effect of ischemia and reperfusion on mitochondrial contact sites in isolated rat hearts
(Murcia : F. Hernández, 1995) Bakker, A.; Goossens, F.; De Bie, M.; Bernaert, I.; Van Belle, H.; Jacob, W.
Contact sites may be described as energy channels between the mitochondria and the cytosol, created by fusion of the inner and the outer mitochondrial membranes, and their number depends highly on the energy state of the cell. The aim of the present study was to examine the early changes of ischemia and reperfusion on the number of mitochondrial contact sites. Therefore isolated rat hearts were subjected to short periods of ischemia followed by reperfusion. The left ventricular pressure (LVP), the contractility (dPIdt,, ) and the heart rate were measured. The number o? contact sites was morphometrically evaluated. As the flow was stopped, LVP, dP/dt and HR declined rapidly and became undetectable a P2 min of ischemia. The number of contact sites fe11 to a minimum after 10 min of ischemia after an initial increase (1 min of ischemia). A 15 min ischemic period resulted in a high number of contact sites which decreased again after 20 min of ischemia. Reperfusion after 2 rnin of ischemia caused an immediate functional recovery and a high presence of contact sites. After 15 rnin of reperfusion, al1 values returned to control values. Reperfusion after 10 rnin of ischemia resulted in a slow recovery of the number of contact sites and after 15 rnin of ischemia the number of contact sites remained low upon reperfusion. We may conclude that mitochondria lose the ability to form contact sites after more than 15 min of ischemia and this might be a first indication of irreversible injury.