Reperfusion injury

Background and Purpose— Hyperperfusion syndrome is a rare but well-described complication after endarterectomy or stenting in the carotid circulation. Summary of Case— A 66-year-old man who had vertebrobasilar insufficiency refractory to medical treatment because of an intracranial right side vertebral stenosis was referred to our institution for endovascular treatment. Stenting was performed, and after 24 hours, he became extremely agitated, and this was followed by a period of apathy without focal neurological deficits. MRI showed bilateral thalamic hemorrhage. Conclusion— To our knowledge, this is the first report of hyperperfusion syndrome with hemorrhagic presentation after intracranial vertebral artery stenting.

Ischemia-reperfusion injury is a pathophysiological event occuring after abdominal organ transplantation, and has a significant influence on prognosis and survival of the graft. It is involved in delaying the primary function or non-functioning of the graft. The objective of this study was to provide information on heat shock protein mechanisms in ischemia-reperfusion injuries in abdominal organ transplantations, and to indicate the possible factors involved that may influence the graft outcome. Several classes of heat shock proteins are part of the ischemia and reperfusion process, both as inflammatory agonists and in protecting the process. Studies involving heat shock proteins enhance knowledge on ischemia-reperfusion injury mitigation processes and the mechanisms involved in the survival of abdominal grafts, and open space to support therapeutic future clinical studies, minimizing ischemia and reperfusion injuries in abdominal organ transplantations. Expression of heat shock proteins is associated with inflammatory manifestations and ischemiareperfusion injuries in abdominal organ transplantations and may influence graft outcomes.

Neutrophil infiltration into inflammatory sites is one of the hallmarks of acute inflammation. Locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration at inflammatory sites. Interleukin-8 (IL-8), a novel leukocyte chemotactic activating cytokine (chemokine), is produced by various types of cells upon stimulation with inflammatory stimuli and exerts a variety of functions on leukocytes, particularly, neutrophils in vitro. However, no definitive evidence has been presented on its role in recruiting and activating neutrophils in the lesions of various types of inflammatory reactions. We administered a highly specific neutralizing antibody against IL-8 in several types of acute inflammatory reactions, including lipopolysaccharide (LPS)-induced dermatitis, LPS/IL-1-induced arthritis, lung reperfusion injury, and acute immune complex-type glomerulonephritis. Anti-IL-8 treatment prevented neutrophil-dependent tissue damage as well as ...

Cerebral ischemia initiates a cascade of detrimental events including glutamate-associated excitotoxicity, intracellular calcium accumulation, formation of Reactive oxygen species (ROS), membrane lipid degradation, and DNA damage, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Cerebral ischemia also triggers acute inflammation, which exacerbates primary brain damage. Therefore, reducing oxidative stress (OS) and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions because clinically effective neuroprotectants have not yet been discovered and no specific therapy for stroke is available to date. Because of their ability to modulate both oxidative stress and the inflammatory response, much attention has been focused on the role of nitric oxide donors (...

Diabetic muscle infarction (DMI) is a rare, long-term complication of poorly controlled diabetes (typically of type I). DMI was first described in 1965 and more than 100 cases have been reported thereafter in the English literature. Usually, there is a coexistence with concomitant nephropathy, neuropathy, and retinopathy. The etiology remains uncertain, but appears to be attributable to diabetic microangiopathy and hypercoagulability and is believed that hypoxia-reperfusion injury is involved. DMI presents with sudden onset of pain associated with a tender mass in the thigh in most instances. The diagnosis is based on magnetic resonance imaging, which is not specific but highly indicative. Treatment is conservative with relapses occurring in 50% of the patients, but not necessarily in the same muscle group. We describe a case of DMI that occurred 4 months after simultaneous kidney and pancreas transplantation in one patient with type I diabetes mellitus and end-stage renal disease.

Abstract:  The pancreas is highly susceptible to the oxidative stress induced by ischemia/reperfusion (IR) injury leading to the generation of acute pancreatitis. Melatonin has been shown to be useful in the prevention of the damage by ischemia-reperfusion in liver, brain, myocardium, gut and kidney. The aim of the study was to evaluate the cytoprotective properties of melatonin against injury induced by IR in pancreas. The obstruction of gastro-duodenal and inferior splenic arteries induced pancreatic IR in male Wistar rats. Melatonin was intraperitoneally administered before or/and after IR injury. The animals were killed at 24 and 48 hr after reperfusion and there were evaluated parameters of oxidative stress (lipoperoxides, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), glandular endocrine and exocrine function (lipase, amylase, insulin) and cell injury (apoptosis and necrosis). The IR induced a marked enhancement of oxidative stress and impaired pancreatic function. The histological analysis showed that IR induced acute pancreatitis with the accumulation of inflammatory infiltrate, disruption of tissue structure, cell necrosis and hemorrhage. Melatonin administration before or after pancreatic IR prevented all tissue markers of oxidative stress, biochemical and histological signs of apoptosis and necrosis, and restored glandular function. No histological signs of pancreatitis were observed 48 hr after reperfusion in 80% of the animals treated with melatonin, with only a mild edematous pancreatitis being observed in the remaining rats. Preventive or therapeutic administration of melatonin protected against the induction of oxidative stress and tissue injury, and restored cell function in experimental pancreatic IR in rats.

The injury caused by reperfusion of ischemic skeletal muscle is mediated by the membrane attack complex of complement (C) . This C activation results from local classical pathway activation after deposition of IgM in injured muscle, an event analogous to C deposition in the mucosa of the gut during reperfusion . Our past analysis has indicated that the injury is not uniform even within a single microscopic section. This study was performed to elucidate the exact site of IgM and C deposition on muscle injured by ischemia and reperfusion. C57Bl/6 mice were subjected to 2 h of tourniquet-induced hindlimb ischemia followed by reperfusion for 0-6 h. Three muscle groups (vastus, gastrocnemius, and soleus) of varying fast-myosin content were compared for muscle fiber damage and C deposition. Adjacent paraffin-embedded cross-sections were immunostained to correlate C3 deposition with muscle fiber type as defined by monoclonal antibodies. Muscle injury after ischemia and reperfusion is not u...

The aim of this study was to determine the effects of a synthetic serine protease inhibitor, gabexate mesilate (GM), in rats with ischemia-reperfusion (I-R) damage due to unilateral testicular torsion. Thirty male Sprague-Dawley rats were separated into three groups, each containing ten rats. A sham operation was performed in group 1 (control). In group 2 (I-R/untreated), 1 h detorsion of the testis was performed after 6 h of unilateral testicular torsion. In group 3 (I-R/GM), after performing the same surgical procedures as in group II, gabexate mesilate was given intravenously. In all experimental rats, ipsilateral orchiectomies were performed for histological examination and measuring the tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). MDA values and the testicular injury score decreased and SOD, CAT and GSH-Px values increased in the GM-treated group compared to the I-R/untreated group. The Tc-99m pertechnetate uptake ratio and the perfusion index were significantly decreased in the group 2 compared to the group 1 and 3 rats. In group 3, these values were significantly increased compared to group 2. Most of the specimens in the GM-treated group showed grade-I testicular injury. However, the injuries in the I-R/untreated rats varied between grade-III and grade-IV. The results of this study show that GM may play a role in reducing the injury caused by I-R.

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially superoxide and hydroxyl radical) and high-energy oxidants (such as peroxynitrite) as mediators of inflammation, shock, and ischemia/reperfusion injury. The aim of this review is to describe recent developments in the field of oxidative stress research. The first part of the review focuses on the roles of reactive oxygen species (ROS) in shock, inflammation, and ischemia/reperfusion injury. The second part of the review deals with the novel findings using recently identified pharmacological tools (e.g., peroxynitrite decomposition catalysts and selective superoxide dismutase mimetics (SODm) in shock, ischemia/reperfusion, and inflammation. 1) The role of ROS consists of immunohistochemical and biochemical evidence that demonstrates the production of ROS in shock, inflammation, and ischemia/reperfusion injury. ROS can initiate a wide range of toxic oxidative reactions. These include initiation...

Standard cardiopulmonary-cerebral resuscitation fails to achieve restoration of spontaneous circulation in approximately 50% of normovolemic sudden cardiac arrests outside hospitals and in essentially all victims of penetrating truncal trauma who exsanguinate rapidly to cardiac arrest. Among cardiopulmonary-cerebral resuscitation innovations since the 1960s, automatic external defibrillation, mild hypothermia, emergency (portable) cardiopulmonary bypass, and suspended animation have potentials for clinical breakthrough effects. Suspended animation has been suggested for presently unresuscitable conditions and consists of the rapid induction of preservation (using hypothermia with or without drugs) of viability of the brain, heart, and organism (within 5 mins of normothermic cardiac arrest no-flow), which increases the time available for transport and resuscitative surgery, followed by delayed resuscitation. Since 1988, we have developed and used novel dog models of exsanguination cardiac arrest to explore suspended animation potentials with hypothermic and pharmacologic strategies using aortic cold flush and emergency portable cardiopulmonary bypass. Outcome evaluation was at 72 or 96 hrs after cardiac arrest. Cardiopulmonary bypass cannot be initiated rapidly. A single aortic flush of cold saline (4 degrees C) at the start of cardiac arrest rapidly induced (depending on flush volume) mild-to-deep cerebral hypothermia (35 degrees to 10 degrees C), without cardiopulmonary bypass, and preserved viability during a cardiac arrest no-flow period of up to 120 mins. In contrast, except for one antioxidant (Tempol), explorations of 14 different drugs added to the aortic flush at room temperature (24 degrees C) have thus far had disappointing outcome results. Profound hypothermia (10 degrees C) during 60-min cardiac arrest induced and reversed with cardiopulmonary bypass achieved survival without functional or histologic brain damage. Further plans for the systematic development of suspended animation include the following: a) aortic flush, combining hypothermia with mechanism-specific drugs and novel fluids; b) extension of suspended animation by ultraprofound hypothermic preservation (0 degrees to 5 degrees C) with cardiopulmonary bypass; c) development of the most effective suspended animation protocol for clinical trials in trauma patients with cardiac arrest; and d) modification of suspended animation protocols for possible use in normovolemic ventricular fibrillation cardiac arrest, in which attempts to achieve restoration of spontaneous circulation by standard external cardiopulmonary resuscitation-advanced life support have failed.

Following successful resuscitation from cardiac arrest, neurological impairment as well as other types of organ dysfunction still cause significant morbidity and mortality. The whole-body ischemia-reperfusion response that occurs during cardiac arrest and subsequent restoration of systemic circulation results in a series of pathophysiological processes that have been termed the post-cardiac arrest syndrome. The components of the post-cardiac arrest syndrome comprise post-cardiac arrest brain injury, post-cardiac arrest myocardial dysfunction, the systemic ischemia-reperfusion response and persistent precipitating pathology. Management of the post-cardiac arrest syndrome involves intensive care support with input from various other medical specialties in a coordinated fashion. Management of ventilation aims for normal carbon dioxide values and normoxia rather than hyperoxia. Management of the circulation commonly requires vasoactive support to overcome (often transient) myocardial dy...

In experiments involving small animals, the electroencephalogram (EEG) recorded during severe injury and accompanying resuscitation exhibit the strong presence of electrocardiogram (ECG). For improved quantitative EEG (qEEG) analysis, it is therefore imperative to remove ECG interference from EEG. In this paper, we validate the use of independent component analysis (ICA) to effectively suppress the interference of ECG from EEG recordings during normal activity, asphyxia and recovery following asphyxia. Two channels of EEG from five rats were recorded continuously for 2 h. Simultaneous recording of one channel ECG was also made. Epochs of 4 s and 1 min were selected from baseline, asphyxia and recovery (every 10 min) and their independent components and power spectra were calculated. The improvement in normalized power spectrum of EEG obtained for all animals was 7.71+/-3.63 db at the 3rd minute of recovery and dropped to 1.15+/-0.60 db at 63rd minute. The application of ICA has been particularly useful when the power of EEG is low, such as that observed during early brain hypoxic-asphyxic injury. The method is also useful in situations where accurate indications of EEG signal power and frequency content are needed.

Objectives Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allograft. We investigated the effect of curcumin on ischemia-reperfusion (I/R) injury and the antioxidant effects of curcumin in rats. Methods Thirty rats were randomly divided into five experimental groups (control, sham, curcumin, I/R and I/R + curcumin, n = 6 each). Curcumin was administered (200 mg kg−1) orally to curcumin and I/R + curcumin groups for 7 days. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 24 h. All rats were killed and kidney function tests, serum and tissue nitric oxide (NO), protein carbonyl (PC), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were determined. Histopathological examinations were also performed. Results Curcumin significantly improved the urea and cystatin C levels in I/R + curcumin group compared to I/R group (p < 0.05). Reduction of serum GSH-Px was significantly improved by curcumin (p < 0.001), but SOD enzyme activity did not alter (p > 0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue MDA, NO and PC and for tissue that were increased by renal I/R injury (p < 0.001 for serum and p < 0.05 for tissue, respectively). In histological examination, the rats treated with curcumin had nearly normal morphology of the kidney. Conclusions Based on our results, it can be concluded that curcumin protects the kidneys against I/R injury via its antioxidant effects.

Ischaemia–reperfusion induces structural and functional damage to hepatocytes. The purpose of this study was to evaluate the protective effect of trimetazidine, an anti- ischaemic drug, in a rat liver model of ischaemia–reperfusion. Male Wistar rats were divided into groups pretreated with different doses of trimetazidine (1, 5, 10 or 20 mg kg−1day−1) or saline for 7 days. Liver ischaemia was induced for 120 min and blood reflow was subsequently restored for 30, 60, 90 or 120 min. The activities of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) as well as the bile flow and the liver ATP content were determined. Ischaemia–reperfusion induced major alterations of hepatic functions involving increases of ASAT and ALAT activities, a drop of ATP content and a sharp decrease in bile flow. Trimetazidine pretreatment reduced the liver injury. Indeed, it lowered the increase in ALAT and ASAT activities observed immediately after reperfusion and maintained higher concentrations of hepatic ATP. Simultaneously, bile flow was increased. These effects were dose-dependent and 5 mg kg−1day−1seemed to be the lowest effective dose. In this experimental model trimetazidine pretreatment reduced the liver damage induced by ischaemia–reperfusion. Our data suggest that trimetazidine may be a useful drug in liver surgery to prevent ischaemia–reperfusion injury.