23 resultados para Hipóxia - Isquemia Encefálica
Resumo:
O transplante pulmonar consolidou-se como a melhor opo teraputica para diversas pneumopatias terminais. O baixo nmero de doadores viveis ainda persiste como uma grande limitao ao aumento do nmero de transplantes de pulmo, causando alta mortalidade na lista de espera. Diferentemente do transplante de outros rgos slidos, a maior limitao do transplante pulmonar no o nmero absoluto de doadores e sim a viabilidade desses rgos, que reduzida devido s agresses ao pulmo ocasionadas pela morte encefálica e aos cuidados na UTI. Diversas so as propostas para o aumento do nmero de doadores: intensificao das campanhas de doao, o uso de doadores com corao parado, transplante pulmonar lobar intervivos e maior flexibilidade dos critrios para aceitao de doadores de pulmo. Todavia, a proposta que atrai a ateno de diversos grupos de transplante pulmonar a perfuso pulmonar ex vivo, principalmente pela perspectiva de recuperao de pulmes inicialmente descartados. Esse sistema consiste na reperfuso e ventilao do bloco pulmonar isolado em um circuito de circulao extracorprea modificado. Devido aos bons resultados apresentados e perspectiva de aumento no nmero de rgos aptos a transplante, diversos grupos tm estudado a tcnica. Pesquisadores na Sucia, Canad, ustria, Inglaterra, Espanha e Brasil j possuem experincia slida com o mtodo e introduziram algumas variaes. O objetivo deste artigo foi revisar o desenvolvimento, o estado da arte e as perspectivas futuras do modelo ex vivo de perfuso e recondicionamento pulmonar.
Resumo:
INTRODUO: H evidncia, embasada por estudos em modelos experimentais de infeco pelo Trypanosoma cruzi, e tambm por investigaes histopatolgicas em humanos com a doena de Chagas, de que distrbios de natureza isqumica participem da patognese de leses miocrdicas na fase crnica da molstia. Esses distrbios isqumicos derivam de desregulao microcirculatria. Dor precordial atpica sintoma comum em pacientes na fase crnica da doena de Chagas. Em substancial proporo desses pacientes, apesar da inexistncia de obstrues coronrias angiograficamente detectveis, documenta-se com cintilografia miocrdica a ocorrncia de distrbios perfusionais durante o estresse, que so reversveis aps repouso. MTODOS: Estudo unicntrico, prospectivo, de coorte nica, com interveno teraputica seguida de reavaliao quantitativa, aps 90 dias, da rea ventricular apresentando alteraes perfusionais isqumicas inicialmente detectadas em pacientes cardiopatas chagsicos com coronrias angiograficamente normais. A cintilografia miocrdica de perfuso ser executada com o mtodo SPECT, antes e aps 90 dias da interveno teraputica, tendo o sestamibi-Tc99m como radiotraador e o esforo fsico ou o estmulo vasodilatador com dipiridamol como estressores. A interveno teraputica consistir de cido acetilsaliclico (dose de 100 mg diria) associado a verapamil (dose diria de 160 mg, em duas tomadas de 80 mg). O desfecho primrio do estudo ser reduo > 50% da rea ventricular de isquemia miocrdica reversvel calculada pelo mapa polar da cintilografia miocrdica de perfuso. CONCLUSES: Este o primeiro estudo de interveno teraputica para atenuar ou reverter alteraes miocrdicas isqumicas de origem microvascular em pacientes com cardiopatia chagsica crnica.
Resumo:
Background Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against Ischemia/Reperfusion (I/R) injury. Type 2 Angiotensin II receptors (AT2R) are shown to be upregulated in cardiac hypertrophy observed in hyperthyroidism and this receptor has been reported to mediate cardioprotection against ischemic injury. Methods The aim of the present study was to evaluate the role of AT2R in the recovery of myocardium after I/R in isolated hearts from T3 treated rats. MaleWistar rats were treated with triiodothyronine (T3; 7 g/100 gBW/day, i.p.) in the presence or not of a specific AT2R blocker (PD123,319; 10 mg/Kg) for 14 days, while normal rats served as control. After treatment, isolated hearts were perfused in Langendorff mode; after 30 min of stabilization, hearts were subjected to 20 min of zero-flow global ischemia followed by 25 min, 35 min and 45 min of reperfusion. Results T3 treatment induced cardiac hypertrophy, which was not changed by PD treatment. Post-ischemic recovery of cardiac function was increased in T3-treated hearts after 35 min and 45 min of reperfusion as compared to control and the ischemic contracture was accelerated and intensified. AT2R blockade was able to return the evaluated functional parameters of cardiac performance (LVDP, +dP/dtmx and dP/dtmin) to the control condition. Furthermore, AT2R blockade prevented the increase in AMPK expression levels induced by T3, suggesting its possible involvement in this process. Conclusion AT2R plays a significant role in T3-induced cardioprotection.
Resumo:
Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). It is not known if pro- and anti-inflammatory mediators in ARDS induced by i-I/R can be controlled by low-level laser therapy (LLLT). This study was designed to evaluate the effect of LLLT on tracheal cholinergic reactivity dysfunction and the release of inflammatory mediators from the lung after i-I/R. Anesthetized rats were subjected to superior mesenteric artery occlusion (45 min) and killed after clamp release and preestablished periods of intestinal reperfusion (30 min, 2 or 4 h). The LLLT (660 nm, 7.5 J/cm(2)) was carried out by irradiating the rats on the skin over the right upper bronchus for 15 and 30 min after initiating reperfusion and then euthanizing them 30 min, 2, or 4 h later. Lung edema was measured by the Evans blue extravasation technique, and pulmonary neutrophils were determined by myeloperoxidase (MPO) activity. Pulmonary tumor necrosis factor- (TNF-), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1), and isoform of NO synthase (iNOS) mRNA expression were analyzed by real-time PCR. TNF-, IL-10, and iNOS proteins in the lung were measured by the enzyme-linked immunoassay technique. LLLT (660 nm, 7.5 J/cm(2)) restored the tracheal hyperresponsiveness and hyporesponsiveness in all the periods after intestinal reperfusion. Although LLLT reduced edema and MPO activity, it did not do so in all the postreperfusion periods. It was also observed with the ICAM-1 expression. In addition to reducing both TNF- and iNOS, LLLT increased IL-10 in the lungs of animals subjected to i-I/R. The results indicate that LLLT can control the lung's inflammatory response and the airway reactivity dysfunction by simultaneously reducing both TNF- and iNOS.
Resumo:
Background: How damaged mitochondria are removed by mitophagy is not fully described. Results: Ischemia and reoxygenation (I/R)-induced injury triggers mitochondria association of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and mitophagy, and protein kinase C (PKC) activation inhibits it. Conclusion: PKC-mediated phosphorylation of GAPDH inhibits mitophagy. Significance: GAPDH/PKC is a signaling switch, which is activated during ischemic injury to regulate the balance between cell survival by mitophagy and cell death by apoptosis.
Resumo:
The activation of heme oxygenase-1 (HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection. In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload (with signs of a chronic hepatitis) and iron deficiency anemia (with paradoxical increased levels of ferritin). Hypoxia induces HO-1 expression in multiple rodent, bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types (endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.
Resumo:
BACKGROUND: Intestinal ischemia followed by reperfusion (I/R) may occur following intestinal obstruction. In rats, I/R in the small intestine leads to structural changes accompanied by neuronal death. AIM: To analyze the impact of I/R injury on different neuronal populations in the myenteric plexus of rat ileum. METHODS: The ileal artery was occluded for 35 min and animals were euthanized 6, 24, and 72 h, and 1 week later. Immunohistochemistry was performed with antibodies against the P2X7 receptor as well as nitric oxide synthase (NOS), calbindin, calretinin, choline acetyltransferase (ChAT), or the pan-neuronal marker anti-HuC/D. RESULTS: Double immunolabeling demonstrated that 100% of NOS-, calbindin-, calretinin-, and ChAT-immunoreactive neurons in all groups expressed the P2X7 receptor. Following I/R, neuronal density decreased by 22.6% in P2X7 receptor-immunoreactive neurons, and decreased by 46.7, 38, 39.8, 21.7, and 20% in NOS-, calbindin-, calretinin-, ChAT-, and HuC/D-immunoreactive neurons, respectively, at 6, 24, and 72 h and 1 week following injury compared to the control and sham groups. We also observed a 14% increase in the neuronal cell body profile area of the NOS-immunoreactive neurons at 6 and 24 h post-I/R and a 14% increase in ChAT-immunoreactive neurons at 1 week following I/R. However, the average size of the calretinin-immunoreactive neurons was reduced by 12% at 6 h post-I/R and increased by 8% at 24 h post-I/R. CONCLUSIONS: This work demonstrates that I/R is associated with a significant loss of different subpopulations of neurons in the myenteric plexus accompanied by morphological changes, all of which may underlie conditions related to intestinal motility disorder
Resumo:
BACKGROUND: Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion. RESULTS: The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10. CONCLUSION: Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal
