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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response to trauma begins in the immune system at the moment of injury. The loci are the wound, with activation of macrophages and production of proinflammatory mediators, and the microcirculation with activation of endothelial cells, blood elements, and a capillary leak. These processes are potentiated by ischemia and impaired oxygen delivery and by the presence of necrotic tissue, each exacerbating the inflammatory response. Hemorrhage alone may be a sufficient stimulus. Inflammation once was considered to be a host reaction to bacteria or other irritants. This concept was expanded by the discovery of autoimmune diseases, and we are now aware that some illnesses are the result of the body's response to an invader rather than the direct effect of the invader itself. The discoveries about the response to trauma described here add another dimension, showing inflammation to be a fundamental life process that begins at the molecular level at the moment of injury and that, depending on the severity of the stimulus and the effectiveness of initial treatment, may spread to include every cell, tissue, and organ in the body, for good or ill. An important part of these expanding concepts is the notion that all noxious stimuli activate the cytokine system as a final common pathway. Sepsis, hemorrhage, ischemia, ischemia-reperfusion, and soft tissue trauma all share an ability to activate macrophages and produce proinflammatory cytokines that may initiate the SIRS. Second-message compounds and effector molecules mediate the observed clinical phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The immune response to trauma. 763 53

Early epidemiologic studies concluded that infection with systemic sepsis was the common pathway for the development of ARDS and eventual MOF. As a consequence, research investigation from 1977 to 1987 focused on later clinical events (e.g., immunosuppression, persistent hypercatabolism, and bacterial translocation). Now, it is believed that an initial massive traumatic insult can create severe SIRS independent of infection (one-hit model). Alternatively, a less severe traumatic insult can create an inflammatory environment (i.e., primes the host) such that a later, otherwise innocuous, secondary inflammatory insult precipitates severe SIRS (two-hit model). As a result of these newer inflammatory models, research interest during the last 5 years has shifted to investigating earlier clinical events (e.g., unrecognized flow-dependent oxygen consumption, ischemia/reperfusion, and priming/activation of the inflammatory response).
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PMID:Evolving concepts in the pathogenesis of postinjury multiple organ failure. 789 97

Despite recent advances in critical care and cardiopulmonary support, mortality from septic shock and its complications remains high. Effective therapies are needed to halt the progression of SIRS and the septic cascade prior to development of shock and organ ischemia/dysfunction. Such therapies are directed at prevention of infection/endotoxemia and modulation of mediators. These therapies are the focus of this article.
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PMID:Mediator-specific therapies for the systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock: present and future approaches. 794 90

Adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF) occur as a result of an unbridled systemic inflammatory response (i.e., severe systemic inflammatory response syndrome [SIRS]). Early epidemiologic studies concluded that infection with systemic sepsis was the common pathway for the development of ARDS and eventual MOF. As a consequence, research investigation from 1977 to 1987 focused on later clinical events (e.g., immunosuppression, persistent hypercatabolism, and bacterial translocation). Now, it is believed that an initial massive traumatic insult can create severe SIRS independent of infection (one-hit model). Alternatively, a less severe traumatic insult can create an inflammatory environment (i.e., primes the host) such that a later, otherwise innocuous, secondary inflammatory insult precipitates severe SIRS (two-hit model). As a result of these newer inflammatory models, research interest over the last 5 yrs has shifted to investigating earlier clinical events (e.g., unrecognized flow-dependent oxygen consumption, ischemia/reperfusion, and priming/activation of the inflammatory response). The traditional infection models of ARDS and MOF are applicable to current research and patient care efforts. However, the inflammatory models emphasize the pivotal role of the initial traumatic insult. Moreover, while ARDS occurs earlier than other types of overt organ failure, it is now believed that simultaneous organ injury is occurring, presumably via similar inflammatory mechanisms.
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PMID:Postinjury multiple organ failure: role of extrathoracic injury and sepsis in adult respiratory distress syndrome. 808 74

Shock is a biological response associated with hypotension and signs of altered tissue perfusion. Shock can be induced by many different mechanisms. Shock itself induces cytokine production as a result of disturbed microcirculation or ischemia-reperfusion injury. Alternatively, severe inflammatory conditions, such as sepsis and severe acute pancreatitis, are usually associated with prominent mediator production, which often leads to shock. TNF-alpha and IL-1 beta increase the vascular permeability, and nitric oxide reduces systemic vascular resistance. In the management of patients who have experienced clinical insult, we must consider the symptoms of systemic inflammatory response syndrome provoked by inflammatory mediators as a warning sign of the development of shock and organ dysfunction. Early withdrawal from SIRS and avoidance of infectious complications (second attack) should be attempted.
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PMID:[Shock and its mediators]. 1057 Jul 77

Hepatic Kupffer cells and pulmonary alveolar macrophages together constitute a macrophage-axis involved in the regulation of regional and systemic inflammatory responses. Systemic inflammatory response syndrome induced by overproduced pro-inflammatory mediators is the major cause of adult respiratory distress syndrome. In the present study, we examined the anti-inflammatory role of nitric oxide (NO) in a rat model of acute lung injury induced by hepatic ischemia-reperfusion (HI/R). The left and median lobes of the liver were subjected to 30 min of ischemia by clamping the relevant branches of hepatic artery and portal vein, followed by a 4-h reperfusion achieved by removal of the vascular clamp. Four groups of animals were studied: sham control + saline; sham control + N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v., 10 min before reperfusion); HI/R + saline; HI/R + L-NAME. Results show that (1) administration of L-NAME to rats subjected to HI/R decreased plasma NO levels; however, the attenuation of NO increased plasma alanine aminotransferase (ALT) activity and superoxide generation in the ischemic lobes of liver, compared to HI/R alone. (2) Inhibition of NO synthesis with L-NAME in rats subjected to HI/R also enhanced systemic inflammatory response as assessed by the increase in the number of circulating leukocytes and levels of plasma tumor necrosis factor-alpha (TNFalpha) and interleukin 1-beta (IL-1beta). (3) The overwhelming systemic inflammatory response induced by administration of L-NAME in rats subjected to HI/R also augmented pulmonary vascular permeability and superoxide generation in the lung tissue. (4) Pulmonary alveolar macrophages isolated from rats subjected to HI/R + L-NAME produced higher levels of TNFalpha and IL-1beta in the supernatant of culture medium than that of rats subjected to HI/R alone. (5) There were no differences between the groups of sham + saline and sham + L-NAME in terms of plasma NO levels and ALT activity, circulating leukocytes, superoxide generation in the liver and lung, lavage protein levels, and TNFalpha and IL-1beta levels in plasma and bronchoalveolar lavage fluid. Our results suggest that inhibition of NO synthesis by L-NAME in rats subjected to HI/R not only augments ischemic liver injury, but also enhances the systemic inflammatory response and exacerbates remote lung injury. The increase in TNFalpha and IL-1beta production by alveolar macrophages may, in part, account for L-NAME-induced enhancement of acute lung injury.
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PMID:Inhibition of nitric oxide synthesis by L-name exacerbates acute lung injury induced by hepatic ischemia-reperfusion. 1153 Oct 23

Beeson (1946) first defined endotoxin tolerance as a reduced endotoxin-induced fever following repeated injections of typhoid vaccine. Freudenberg and Galanos (1988) demonstrated that endotoxin tolerance that can protect against a lethal challenge of lipopolysaccharide (LPS) involves the participation of macrophages. Evans and Zuckerman (1991) reported a role for glucocorticoids in endotoxin tolerance. Prostaglandins, interleukin-(IL-)10, and transforming growth factor-beta are other players of in vivo endotoxin tolerance. Dramatic reduction of plasma tumor necrosis factor (TNF) (Mathison et al. 1990) and other cytokines in response to LPS parallels endotoxin tolerance. The reduced capacity to produce TNF and other cytokines can be mimicked in vitro by pretreatment of monocytes or macrophages with LPS. It is not a specific phenomenon and can be induced by other agents or events. Cross-tolerance between LPS, TLR2 specific ligands, IL-1 and TNF has been regularly reported. A similar loss of LPS-reactivity has been repeatedly reported in leukocytes of septic patients and in patients with non-infectious systemic inflammation response syndrome (SIRS; e.g. surgery, trauma, cardiac arrest and resuscitation, etc.). Studies on cellular signaling within leukocytes from septic and SIRS patients reveal numerous alterations of the activation pathways reminiscent of those observed in endotoxin-tolerant cells. While endotoxin tolerance prevents severity of infections and ischemia-reperfusion damage, it has been suggested that the immune dysregulation observed in SIRS patients was associated with an enhanced sensitivity to nosocomial infections. In conclusion, in vitro and in vivo endotoxin tolerance, either experimental or due to clinical status, are similar but not identical.
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PMID:Endotoxin tolerance: is there a clinical relevance? 1280 83

Myocardial I-R injury contributes to adverse cardiovascular outcomes after cardiac surgery. The pathogenesis of I-R injury is complex and involves the activation, coordination, and amplification of several systemic and local proinflammatory pathways (Fig. 4). Treatment and prevention of perioperative morbidity associated with myocardial I-R will ultimately require a multifocal approach. Combining preoperative risk stratification (co-morbidity and surgical complexity), minimizing initiating factors predisposing to SIRS, limiting ischemia duration, and administering appropriate immunotherapy directed toward systemic and local proinflammatory mediators of I-R injury, should all be considered. In addition, the role of the genetic-environmental interactions in the pathogenesis of cardiovascular disease is also being examined. Thus, in the near future, preoperative screening for polymorphisms of certain inflammatory and coagulation genes should inevitably help reduce morbidity by permitting the identification of high-risk cardiac surgical patients and introducing the opportunity for gene therapy or pharmacogenetic intervention [42,64].
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PMID:Perioperative myocardial ischemia reperfusion injury. 1456 61

The induction of heme oxygenase (HO), the rate limiting enzyme in the conversion of heme into carbon monoxide (CO) and biliverdin, limits liver injury following remote trauma such as hind limb ischemia/reperfusion (I/R). Using intravital video microscopy, we tested the hypothesis that inhaled CO (250 ppm) would mimic HO-derived liver protection. Hind limb I/R significantly decreased sinusoidal diameter and volumetric flow, increased leukocyte accumulation within sinusoids, increased leukocyte rolling and adhesion within postsinusoidal venules, and significantly increased hepatocyte injury compared with naive animals. Inhalation of CO alone did not alter any microcirculatory or inflammatory parameters. Inhalation of CO following I/R restored volumetric flow, decreased stationary leukocytes within sinusoids, decreased leukocyte rolling and adhesion within postsinusoidal venules, and significantly reduced hepatocellular injury following hind limb I/R. HO inhibition did not alter microcirculatory parameters in naive mice, but did increase inflammation, as well as increase hepatocyte injury following hind limb I/R. Inhalation of CO during HO inhibition significantly reduced such microcirculatory deficits, hepatic inflammation, and injury in response to hind limb I/R. In conclusion, these results suggest that HO-derived hepatic protection is mediated by CO, and inhalation of low concentrations of CO may represent a novel therapeutic approach to prevent remote organ injury during systemic inflammatory response syndrome, or SIRS.
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PMID:Inhalation of carbon monoxide prevents liver injury and inflammation following hind limb ischemia/reperfusion. 1551 2

There were strong evidences that NO has capital importance in the progressive vasodilatation that associates to the varied circulatory shock forms. The decreased systemic vascular resistance observed in irreversible hemorrhagic (hypovolemic) and septic shock may be due to the excess production of nitric oxide. Other forms of shock associated to anaphylaxis (anaphylactic shock, SIRS) and ischemia reperfusion injury (cardiogenic shock, organ transplants), may involve nitric oxide overproduction. In these situations, the nitric oxide-induced loss of vascular sensitivity to catecholamines and myocardial depression contributes to lethal hypotension. As NO vasodilatation is cyclic GMP-mediated, there were two therapeutical options: a) The unspecific NO synthesis inhibition by L-arginine analogs, iNOS-specific inhibition by corticoids and/or aminoguanidine and; b) Guanylyl cyclase inhibition by MB. As the NO synthesis inhibition is associated to tissue necrosis and adverse hemodynamic effects and its clinical use was associated with high mortality, the second option using MB is safer and more rational. The elaboration of this text was motivated to suggest the guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target.
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PMID:The guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target. 1701 95


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