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Ischaemia
Kinds of Ischaemia Terms modified by Ischaemia Selected AbstractsDAMAGE CONTROL SURGERY AND ANGIOGRAPHY IN CASES OF ACUTE MESENTERIC ISCHAEMIAANZ JOURNAL OF SURGERY, Issue 5 2005Anthony J. Freeman Background: Acute mesenteric arterial occlusion typically presents late and has an estimated mortality of 60,80%. This report examines the evolution of a novel management approach to this difficult surgical problem at a teaching hospital in rural Australia. Methods: A retrospective review of 20 consecutive cases that presented to Lismore Base Hospital, Lismore, New South Wales, between 1995 and 2003 was performed. Results: Of the 16 patients who were actively treated, 10 survived. Mortality was associated with attempting an emergency operative revascularisation and not performing a second-look laparotomy. All three patients who had a damage control approach at the initial operation survived and in four cases endovascular intervention successfully achieved reperfusion of acutely ischaemic bowel. Conclusions: Evidence from the series of patients described suggests that damage control surgery and early angiography improve survival in patients suffering acute mesenteric ischaemia. A damage control approach involves emergency resection of ischaemic bowel with no attempt to restore gastrointestinal continuity and formation of a laparostomy. Patients are stabilised in the intensive care unit (ICU) and angiography can be arranged to either plan a definitive bypass procedure or alternatively endovascular therapies can be carried out in an attempt to arrest gastrointestinal infarction. Definitive surgery is then considered after 2,3 days. This approach is particularly attractive if immediate specialist vascular expertise is not available. [source] MODULATION OF SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT) FACTOR PATHWAYS DURING FOCAL CEREBRAL ISCHAEMIA: A GENE EXPRESSION ARRAY STUDY IN RAT HIPPOCAMPUS AFTER MIDDLE CEREBRAL ARTERY OCCLUSIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007Sheng-Li Sun SUMMARY 1Signal transducers and activators of transcription (STAT) factors are a family of transcription factors that mediate intracellular signalling initiated at cytokine cell surface receptors and transmitted to the nucleus. In the present study, we determined the global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion using microarray analysis. 2The present study used middle cerebral artery occlusion (MCAO) to induce ischaemia and reperfusion in Sprague-Dawley rats. Using superarray Q series Janus tyrosine kinases (Jak)/STAT signalling pathway gene array, a total of 96 genes was screened in adult male rat hippocampus after transient focal cerebral ischaemia. 3The results showed that 23 genes were upregulated at least twofold by ischaemia treatment and that 12 genes were downregulated at least threefold by ischaemia treatment compared with controls. 4After confirmation by quantitative real-time polymerase chain reaction, the data suggest that the gene expression of STAT2, 5a, 5b, 6 and suppressor of cytokine signalling (SOCS) 4 was increased by ischaemia, probably due to a compensatory response of the brain, which may play a protective role in damaged brain tissue. 5The results of the present study provide evidence on global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion, in which STAT2, 5a, 5b, 6 and SOCS4 were confirmed to be significantly modulated during focal cerebral ischaemia. [source] ROSIGLITAZONE, AN AGONIST OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA, PREVENTS CONTRALATERAL TESTICULAR ISCHAEMIA,REPERFUSION INJURY IN PREPUBERTAL RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2007Mustafa Inan SUMMARY 1Rosiglitazone plays a positive role in the reparation of ischaemia,reperfusion (I/R) injury in different tissues. Thus, we examined its biochemical and histological effects on the contralateral testes to determine whether exogenous rosiglitazone affords any protection against testicular damage. 2Forty-eight prepubertal male Wistar-Albino rats were divided into six groups. Testicular torsion was created by rotating the right testis 720° in a clockwise direction for 5 h in all groups except group I, which was the sham-control group. In group II, bilateral orchiectomy was performed following the torsion period. After detorsion both testes were removed in the fifth hour in group III and on the seventh day in group IV. In group V, one-shot rosiglitazone (4 mg/kg) was administered 40 min before detorsion and both testes were removed following the torsion period. In group VI, rosiglitazone was administered (4 mg/kg) 40 min before detorsion and for 7 days, and then both testes were harvested. The tissue levels of malondialdehyde (MDA) were measured and mean testicular biopsy score (MTBS) and mean seminiferous tubule diameter (MSTD) were examined. Immunoexpression of endothelial nitric oxide synthase (eNOS) in testes tissues was investigated by immunohistochemical studies. 3In the contralateral testis, the MTBS and MSTD values of group VI were significantly higher than those in group IV. Immunohistochemically, mild eNOS immunostaining was present in the germ cells of the contralateral testes in group IV after I/R. In group VI, intense eNOS immunoreactivity was seen in the contralateral testes. 4Rosiglitazone reduces contralateral testicular damage formed after unilateral testicular torsion and alleviates the oxidative events. [source] Impaired glucose regulation, elevated glycated haemoglobin and cardiac ischaemic events in vascular surgery patientsDIABETIC MEDICINE, Issue 3 2008H. H. H. Feringa Abstract Aims Cardiac morbidity and mortality is high in patients undergoing high-risk surgery. This study investigated whether impaired glucose regulation and elevated glycated haemoglobin (HbA1c) levels are associated with increased cardiac ischaemic events in vascular surgery patients. Methods Baseline glucose and HbA1c were measured in 401 vascular surgery patients. Glucose < 5.6 mmol/l was defined as normal. Fasting glucose 5.6,7.0 mmol/l or random glucose 5.6,11.1 mmol/l was defined as impaired glucose regulation. Fasting glucose , 7.0 or random glucose , 11.1 mmol/l was defined as diabetes. Perioperative ischaemia was identified by 72-h Holter monitoring. Troponin T was measured on days 1, 3 and 7 and before discharge. Cardiac death or Q-wave myocardial infarction was noted at 30-day and longer-term follow-up (mean 2.5 years). Results Mean (± sd) level for glucose was 6.3 ± 2.3 mmol/l and for HbA1c 6.2 ± 1.3%. Ischaemia, troponin release, 30-day and long-term cardiac events occurred in 27, 22, 6 and 17%, respectively. Using subjects with normal glucose levels as the reference category, multivariate analysis revealed that patients with impaired glucose regulation and diabetes were at 2.2- and 2.6-fold increased risk of ischaemia, 3.8- and 3.9-fold for troponin release, 4.3- and 4.8-fold for 30-day cardiac events and 1.9- and 3.1-fold for long-term cardiac events. Patients with HbA1c > 7.0% (n = 63, 16%) were at 2.8-fold, 2.1-fold, 5.3-fold and 5.6-fold increased risk for ischaemia, troponin release, 30-day and long-term cardiac events, respectively. Conclusions Impaired glucose regulation and elevated HbA1c are risk factors for cardiac ischaemic events in vascular surgery patients. [source] In vitro effects of lidocaine on the contractility of equine jejunal smooth muscle challenged by ischaemia-reperfusion injuryEQUINE VETERINARY JOURNAL, Issue 1 2010M. GUSCHLBAUER Summary Reasons for performing study: Post operative ileus (POI) in horses is a severe complication after colic surgery. A commonly used prokinetic drug is lidocaine, which has been shown to have stimulatory effects on intestinal motility. The cellular mechanisms through which lidocaine affects smooth muscle activity are not yet known. Objectives: To examine the effects of lidocaine on smooth muscle in vitro and identify mechanisms by which it may affect the contractility of intestinal smooth muscle. Hypothesis: Ischaemia and reperfusion associated with intestinal strangulation can cause smooth muscle injury. Consequently, muscle cell functionality and contractile performance is decreased. Lidocaine can improve basic cell functions and thereby muscle cell contractility especially in ischaemia-reperfusion-challenged smooth muscle. Methods: To examine the effects of lidocaine on smooth muscle function directly, isometric force performance was measured in vitro in noninjured and in vivo ischaemia-reperfusion injured smooth muscle tissues. Dose-dependent response of lidocaine was measured in both samples. To assess membrane permeability as a marker of basic cell function, release of creatine kinase (CK) was measured by in vitro incubations. Results: Lidocaine-stimulated contractility of ischaemia-reperfusion injured smooth muscle was more pronounced than that of noninjured smooth muscle. A 3-phasic dose-dependency was observed with an initial recovery of contractility especially in ischaemia-reperfusion injured smooth muscle followed by a plateau phase where contractility was maintained over a broad concentration range. CK release was decreased by lidocaine. Conclusion: Lidocaine may improve smooth muscle contractility and basic cell function by cellular repair mechanisms which are still unknown. Improving contractility of smooth muscle after ischaemia-reperfusion injury is essential in recovery of propulsive intestinal motility. Potential relevance: Characterisation of the cellular mechanisms of effects of lidocaine, especially on ischaemia-reperfusion injured smooth muscle, may lead to improved treatment strategies for horses with POI. [source] Ischaemia or reperfusion: which is a main trigger for changes in nitric oxide mRNA synthases expression?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2005D. Pevni Abstract Objective, To investigate alterations in endothelial nitric oxide synthase and inducible nitric oxide synthase mRNA expressions and nitric oxide release in the myocardium during ischaemia/reperfusion and determine whether these changes are ischaemic and/or reperfusion dependent. Materials and methods, Isolated rat hearts were perfused by a modified Langendorff system. Following 1 h of global cardioplegic ischaemia, left ventricle haemodynamic parameters were recorded at baseline and during 30 min of reperfusion. Levels of endothelial, inducible nitric oxide synthases mRNA expression and nitric oxide release were measured at baseline, after ischaemia and at 30 min of reperfusion. Results, Global cardioplegic ischaemia caused a significant depression of left ventricular function and a decrease of coronary flow. Postischaemic intensities of the endothelial nitric oxide synthase mRNA bands were significantly lower than at baseline (P < 0·01). There were no significant differences in endothelial nitric oxide synthase mRNA band intensities immediately after ischaemia compared to the end of reperfusion, nor between the intensities of inducible nitric oxide synthase mRNA bands at baseline, at end of ischaemia and at end of reperfusion. Nitric oxide in the myocardial effluent was below detectable levels at all measured points. Conclusion, Ischaemic injury causes down-regulation of endothelial nitric oxide synthase mRNA expression, which is then associated with reduction of coronary flow during reperfusion, representing one possible mechanism of ischaemia/reperfusion injury. We did not find expected elevations of inducible nitric oxide synthase mRNA expression during ischaemia or reperfusion and we suggest that ischaemia/reperfusion injury is not associated with nitric oxide overproduction. [source] Differential regulation of the nitric oxide,cGMP pathway exacerbates postischaemic heart injury in stroke-prone hypertensive ratsEXPERIMENTAL PHYSIOLOGY, Issue 1 2007Tetsuji Itoh Using a working perfused heart model, we investigated the hypothesis that alterations in the NO,cGMP pathway may exacerbate postischaemic mechanical dysfunction in the hypertrophied heart. Ischaemia for 25 min followed by reperfusion for 30 min produced marked cardiac mechanical dysfunction in both stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). Exogenous treatment with S -nitroso- N -acetyl- dl -penicillamine (SNAP), a NO donor, had beneficial effects on the cardiac dysfunction induced by ischaemia,reperfusion (I/R) in the WKY heart, but the cardioprotective effect of SNAP was eliminated by guanylyl cyclase inhibitor. Cardiac cGMP levels were increased by SNAP or ischaemia in WKY. In contrast, in SHRSP hearts, SNAP could not alleviate the cardiac dysfunction caused by I/R. Pre-ischaemia, the cardiac cGMP level was significantly higher in SHRSP than in WKY; however, no significant difference was found after SNAP and ischaemia. The myocardial Ca2+ -dependent NO synthase (NOS) activity increased at the end of ischaemia in WKY. Conversely, the Ca2+ -independent NOS activity and protein levels were upregulated by I/R in the SHRSP myocardium. In the SHRSP hearts, non-selective NOS and selective Ca2+ -independent NOS inhibitors or antioxidant treatment alleviated cardiac dysfunction caused by I/R. Moreover, mRNA expression and Western blotting analysis of cGMP-dependent protein kinase type I showed more deterioration of SHRSP hearts compared with WKY. These results suggest that: (1) the NO-dependent cardioprotective effect is depressed; and (2) overproduction of NO derived from Ca2+ -independent NOS contributes to postischaemic heart injury in the hypertrophied heart of hypertensive status. [source] Effects of Ischaemia on Subsequent Exercise-Induced Oxygen Uptake Kinetics in Healthy Adult HumansEXPERIMENTAL PHYSIOLOGY, Issue 2 2002Michael L. Walsh Leg muscles were occluded (33 kPa) prior to exercise to determine whether the induced metabolic changes, and reactive hyperaemia upon occlusion release just prior to the exercise, would accelerate the subsequent oxygen consumption (V,O2) response. Eight subjects performed double bouts (6 min duration, 6 min rest in-between) of square wave leg cycle ergometry both below and above their lactate threshold (LT). Prior to exercise, large blood pressure cuffs were put around the upper thighs. Occlusion durations were 0 min (control), 5 min and 10 min. Ischaemia was terminated within 5 s prior to exercise onset. Heart rate, V,O2, ventilatory rate (V,E), electromyogram (EMG) and haemoglobin/myoglobin (Hb/Mb) saturation were recorded continuously. Single exponential modelling demonstrated that, compared to control (time constant = 53.9 ± 13.9 s), ischaemia quickened the V,O2 response (P < 0.05) for the first bout of exercise above LT (time constant = 48.3 ± 14.5 s) but not to any other exercise bout below or above LT. The 3-6 min integrated EMG (iEMG) slope was correlated to the 3-6 min V,O2 slope (r = 0.73). Hb/Mb saturation verified the ischaemia but did not show a consistent relation to the V,O2 time course. Reactive hyperaemia induced a faster V,O2 response for work rates above LT. The effect, while significant, was not large considering the expected favourable metabolic and circulatory changes induced by ischaemia. [source] Bacopa monniera protects rat heart against ischaemia,reperfusion injury: role of key apoptotic regulatory proteins and enzymesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2010Ipseeta Ray Mohanty Abstract Objectives, Rat isolated hearts were perfused in a Langendorff model to study the cardioprotective effects of Bacopa monniera, a medicinal herb used in the Indian system of medicine, on cardiomyocyte apoptosis and antioxidant status following ischaemia,reperfusion (I-R) injury. Methods, Forty-eight rats were randomly divided into four groups (12 in each group): sham group (no ischaemia,reperfusion injury), B. monniera control group (orally fed B. monniera at a dose of 75 mg/kg, for three weeks); ischaemia,reperfusion control group(subjected to ischaemia,reperfusion-induced myocardial injury) and B. monniera -treated group (same protocol as ischaemia,reperfusion control group except that rats also fed B. monniera). Key findings, Post-ischaemic reperfusion injury resulted in significant cardiac necrosis, apoptosis, depression of heart rate, decline in antioxidant status and elevation in lipid peroxidation. Oral administration of B. monniera per se for three weeks to healthy rats caused augmentation of myocardial antioxidants, superoxide dismutase, catalase and glutathione, along with induction of heat shock protein 72 (HSP72). Ischaemia,reperfusion-induced biochemical and histopathological perturbations were significantly prevented by B. monniera (75 mg/kg) pre-treatment. Interestingly, B. monniera also restored the antioxidant network of the myocardium and reduced myocardial apoptosis, caspase 3 and Bax protein expression. Conclusions, Histopathological studies and myocardial creatine phosphokinase content further confirmed the cardioprotective effects of B. monniera (75 mg/kg) in the experimental model of ischaemia,reperfusion injury. The study provides scientific basis for the putative therapeutic effect of B. monniera in ischaemic heart disease. [source] Preconditioning protects the guinea-pig urinary bladder against ischaemic conditions in vitroNEUROUROLOGY AND URODYNAMICS, Issue 7 2003Bruno Lorenzi Abstract Aims To investigate the ability of ischaemic preconditioning (IPC) to protect guinea-pig detrusor from damage caused by a subsequent more prolonged exposure to ischaemic conditions. Materials and Methods Smooth muscle strips were mounted for tension recording in small organ baths continuously superfused with Krebs' solution at 37°C. Ischaemia was mimicked by removing oxygen and glucose from the superfusing solution. Contractile responses to electrical field stimulation (EFS) and carbachol were monitored. Three regimes of preconditioning were examined: 15, 10, and 5 min of ischaemic conditions followed by 15, 10, and 5 min of normal conditions, respectively. Results Without preconditioning, nerve-mediated responses were significantly and proportionally reduced by periods of ischaemic conditions lasting for 45, 60, and 90 min, but recovered fully after exposure to ischaemic conditions for 30 min. The recovery of the responses to EFS was significantly improved in preconditioned strips when the period of ischaemic conditions was 45 or 60 min. However, no significant differences were seen with preconditioning when the period of ischaemic conditions was 90 min. The recovery of responses to carbachol was much greater than for the responses to EFS, and no significant differences were found between control and preconditioned strips. Conclusions It is suggested that in vivo short periods of transient ischaemia may be able to protect the guinea-pig bladder from the impairment associated with longer periods of ischaemia and reperfusion, which might happen in obstructed micturition. Our results also indicate that the phenomenon affects mainly the intrinsic nerves, which are more susceptible to ischaemic damage than the smooth muscle. Neurourol. Urodynam. 22:687,692, 2003. © 2003 Wiley-Liss, Inc. [source] Hypoxic preconditioning protects rat hearts against ischaemia,reperfusion injury: role of erythropoietin on progenitor cell mobilizationTHE JOURNAL OF PHYSIOLOGY, Issue 23 2008Jih-Shyong Lin Preconditioning, such as by brief hypoxic exposure, has been shown to protect hearts against severe ischaemia. Here we hypothesized that hypoxic preconditioning (HPC) protects injured hearts by mobilizing the circulating progenitor cells. Ischaemia,reperfusion (IR) injury was induced by left coronary ligation and release in rats kept in room air or preconditioned with 10% oxygen for 6 weeks. To study the role of erythropoietin (EPO), another HPC + IR group was given an EPO receptor (EPOR) antibody via a subcutaneous mini-osmotic pump 3 weeks before IR induction. HPC alone gradually increased haematocrit, cardiac and plasma EPO, and cardiac vascular endothelial growth factor (VEGF) only in the first two weeks. HPC improved heart contractility, reduced ischaemic injury, and maintained EPO and EPOR levels in the infarct tissues of IR hearts, but had no significant effect on VEGF. Interestingly, the number of CD34+CXCR4+ cells in the peripheral blood and their expression in HPC-treated hearts was higher than in control. Preconditioning up-regulated cardiac expression of stromal derived factor-1 (SDF-1) and prevented its IR-induced reduction. The EPOR antibody abolished HPC-mediated functional recovery, and reduced SDF-1, CXCR4 and CD34 expression in IR hearts, as well as the number of CD34+CXCR4+ cells in blood. The specificity of neutralizing antibody was confirmed in an H9c2 culture system. In conclusion, exposure of rats to moderate hypoxia leads to an increase in progenitor cells in the heart and circulation. This effect is dependent on EPO, which induces cell homing by increased SDF-1/CXCR4 and reduces the heart susceptibly to IR injury. [source] Evidence that endogenous inosine and adenosine-mediated hyperglycaemia during ischaemia,reperfusion through A3 adenosine receptorsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2009D. Cortés Summary 1,The molecular mechanism underlying stress-induced hyperglycemia has not been comprehensively clarified. Recently, we demonstrated in ischaemia-reperfusion (I-R) stress-subjected liver that inosine and adenosine are mainly responsible for the hyperglycemia observed. 2,We aimed to advance in the knowledge of the role of inosine plus adenosine as mediators of hepatic-induced hyperglycemia detected after I-R in lower limbs. 3,Acute ischaemia was conducted in anesthetized rats by occluding downstream abdominal aorta and cava vein; then, reperfusion was allowed. Blood samples from hepatic or abdominal cava veins were taken throughout the experiments to measure glucose, inosine and adenosine. Antagonists to adenosine (AdoR) and adrenergic receptors (AdrR) were administered during ischaemia to analyze their effect on hepatic glucose release. 4,Ischaemia up to 60 min produced minor increase of glucose and nucleosides blood values, but 5 min of ischaemia followed by 2- (or 10-) min reperfusion increased glucose 23%, and those of inosine or adenosine by 100%. After 60 min of ischaemia and 10 min of reperfusion, glycemia rose 2-fold and blood inosine and adenosine, 3.3- and 2.7-fold, respectively. A linear positive correlation, r2, as high as 0.839 between glucose and either nucleoside blood values was calculated. The hyperglycemia response to I-R decreased by 0, 25, 33, 45 and 100% after selective inhibition of A2B AdoR, A2A AdoR, a1B AdrR, A1 AdoR, and A3 AdoR, respectively. 5,Inosine-adenosine couple through activation of hepatic A3 AdoR is the main signal for releasing glucose from liver glycogen and for promoting hyperglycemia following experimental injury of I-R from lower limbs. [source] Mechanisms of Preventive Effect of Nicorandil on Ischaemia-Induced Ventricular Tachyarrhythmia in Isolated Arterially Perfused Canine Left Ventricular WedgesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Masamichi Hirose We examined effects of nicorandil on the induction of VT during acute myocardial ischaemia. Optical action potentials were recorded from the entire transmural wall of arterially perfused canine left ventricular wedges. Ischaemia was produced by arterial occlusion for 20 min. During endocardial pacing, nicorandil shortened mean action potential duration (APD) in the transmural wall before ischaemia and further shortened it during ischaemia without increasing dispersion of APD. HMR1098, a selective blocker of sarcolemmal ATP-sensitive K+ channels, inhibited the shortening of APD by nicorandil before and during ischaemia. Ischaemia decreased transmural conduction velocity (CV). Nicorandil partially restored CV to a similar extent in the absence and presence of HMR1098. In contrast, HMR1098 did not suppress the ischaemic conduction slowing in the absence of nicorandil. Nicorandil suppressed the increased dispersion of local CV during ischaemia. Isochrone maps on the initiation of VT showed that reentry in the transmural surface resulted from the excitation of the epicardial region of transmural surface. Nicorandil significantly increased the size of non-excited area in the epicardial region of the transmural wall, thereby significantly reducing the incidence of VT induced during ischaemia. HMR1098 inhibited this effect of nicorandil. These results suggest that nicorandil prevents VT during acute global ischaemia primarily by augmenting the inactivation of epicardial muscle through the activation of sarcolemmal KATP channels. [source] The Role of Myocardial KATP -Channel Blockade in the Protective Effects of Glibenclamide against Ischaemia in the Rat HeartBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2002Roger J. Legtenberg This study addresses the possible involvement of KATP channels in this beneficial action of glibenclamide. We hypothesized that if glibenclamide improved postischaemic cardiac function by blocking of KATP channels, opening of these KATP channels should result in the opposite, namely detrimental effects on postischaemic heart function. Postischaemic functional loss and coronary blood flow were recorded during treatment with glibenclamide (4 ,mol.l,1; n=5), the KATP channel openers pinacidil (1 ,mol.l,1; n=5) and diazoxide (30 ,mol.l,1; n=5), the combination of glibenclamide with pinacidil (n=5) and glibenclamide with diazoxide (n=5), and vehicle (n=8). Both pinacidil and diazoxide significantly increased coronary blood flow 2,3 times, which was abolished by glibenclamide pre- and postischaemically. This confirms that under both flow conditions glibenclamide significantly blocks KATP channels in the coronary vasculature. The 12 min. global ischaemic incident resulted in a cardiac functional loss of 22.2±2.9% during vehicle. Glibenclamide reduced the cardiac functional loss to 4.3±1.2% (P<0.01). Interestingly, both pinacidil and diazoxide reduced the cardiac functional loss to 4.0±1.5% (P<0.01) and 2.9±1.4% (P<0.001), respectively. The combination pinacidil+glibenclamide resulted in additional protection compared with the individual components (0.6±0.1 versus 4.0±1.5%, P<0.05). Thus, in contrast to its effect on coronary vascular tone, the glibenclamide-induced improvement of postischaemic cardiac function may not be mediated through blockade of the KATP channel. Alternative mechanisms may be operative, such as uncoupling of the mitochondrial respiratory chain, thereby preconditioning the hearts against stunning. [source] Ischaemic preconditioning improves microvascular perfusion and oxygenation following reperfusion injury of the intestine,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2005I. H. Mallick Background: Ischaemia,reperfusion (IR) injury of the intestine occurs commonly during abdominal surgery. Ischaemic preconditioning (IPC) provides a way of protecting the organ from damage inflicted by IR. This study was designed to evaluate the beneficial effect of IPC, focusing on the intestinal microcirculation and oxygenation in intestinal IR injury. Methods: Rats were allocated to three groups. Animals in the IR and IPC groups underwent 30 min of intestinal ischaemia followed by 2 h of reperfusion. In the IPC group this was preceded by 10 min of ischaemia and 10 min of reperfusion. Animals in the third group underwent laparotomy but no vascular occlusion. Intestinal microvascular perfusion, oxygenation and portal venous blood flow (PVF) were monitored continuously. At the end of the reperfusion period, blood samples were obtained for measurement of lactate dehydrogenase (LDH) and biopsies of ileum for histological evaluation. Results: IPC improved intestinal microvascular perfusion and tissue oxygenation significantly at the end of the reperfusion period (P < 0·001). PVF improved significantly in the IPC compared with the IR group (P = 0·005). The serum LDH concentration was significantly lower in the IPC than the IR group (mean(s.e.m.) 667·1(86·8) versus 1973·8(306·5) U/l; P < 0·001) Histological examination showed that ileal mucosa was significantly less injured in the IPC group. Conclusions: This study demonstrated that IPC improves intestinal microvascular perfusion and oxygenation. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Pro- and anti-inflammatory cytokine release in open versus endovascular repair of abdominal aortic aneurysmBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2001T. E. Rowlands Background: Pro- and anti-inflammatory cytokine release occurs with abdominal aortic aneurysm (AAA) repair although the relative contribution of each is currently poorly understood. Ischaemia,reperfusion injury is thought to play a greater role following open (OR) than endovascular (ER) repair, with resultant greater perioperative morbidity. Methods: Thirty-two patients undergoing OR (n = 16) and ER (n = 16) of AAA were studied. Systemic venous (SV) blood was taken at induction (baseline), 0 h (last clamp off), 4, 24, 72 and 144 h, and femoral venous (FV) blood (indwelling catheter; lower torso venous effluent) at 0, 4 and 24 h. The cytokines interleukin (IL) 6, IL-8 and IL-10 were measured in these samples. Results: In OR, SV and FV IL-6 increased from baseline to a peak at 24 h (SV 589 pg/ml (P = 0·001 versus baseline) and FV 848 pg/ml (P = 0·05)) before declining at 144 h. In ER, there was a similar pattern but the increase was smaller (24 h: SV 260 pg/ml (P = 0·003 versus baseline) and FV 319 pg/ml (P = 0·06)) at all equivalent timepoints compared with OR. IL-8 peaked earlier (4 h) from baseline in both groups before declining by 144 h, and significant differences between SV and FV were seen only in the OR group. IL-10 levels peaked in both groups at 24 h before declining at 144 h, and there were no significant locosystemic differences between the groups. Conclusion: Venous pro-inflammatory cytokine changes (IL-6) are consistent with significantly greater lower-torso reperfusion injury in patients undergoing OR. Smaller responses were seen after ER (IL-6 and IL-8), although both groups showed a similar anti-inflammatory response (IL-10); this pro- and anti-inflammatory imbalance may account for the increased morbidity assoicated with OR. © 2001 British Journal of Surgery Society Ltd [source] Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brainCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2003M. Kemal Irmak Abstract Oxygen-derived free radicals have been implicated in the pathogenesis of cerebral injury after ischaemia,reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. The purpose of the present study was to investigate the effects of ischaemia and subsequent reperfusion on rat brain and to investigate the effects of two free radical scavengers, CAPE and alpha-tocopherol, on this in vivo model of cerebral injury. Ischaemia was induced by bilateral occlusion of the carotid arteries for 20,min and reperfusion was achieved by releasing the occlusion to restore the circulation for 20,min. Control rats underwent a sham operation. CAPE at 10,,;mol,kg,1 or alpha-tocopherol at 25,,mol,kg,1 was administered intraperitoneally before reperfusion. Reperfusion led to significant increase in the activity of xanthine oxidase and higher malondialdehyde levels in the brain. Acute administration of both CAPE and alpha-tocopherol suppressed ischaemia,reperfusion-induced cerebral lipid peroxidation and injury, but CAPE seems to offer a better therapeutic advantage over alpha-tocopherol. Copyright © 2003 John Wiley & Sons, Ltd. [source] Larval therapy as a palliative treatment for severe arteriosclerotic gangrene on the feetCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 8 2009A. Nordström Summary Larval therapy (LT) is known to be a gentle and effective method for removing necrotic tissue and bacteria and reducing the accompanying unpleasant odour. Ischaemia has been considered a relative contraindication for LT. We report a patient with ischaemia treated with LT. Inguinal revascularization was performed on a 69-year-old man with critical limb ischaemia, diabetes mellitus, heart failure and end-stage renal disease. Areas of dry black malodorous gangrene remained on the distal areas of the feet after surgery and the patient's poor health did not allow any additional surgery. The patient was referred to the dermatology department for LT. Although patients are usually given this treatment as inpatients, the patient requested treatment at home. After the first LT, there was a marked reduction in odour. The gangrene needed repeated applications of larvae to remove the dead tissue. After eight treatments, the result was more positive than we had expected, with total lack of odour and initiation of healing. Larvae cannot penetrate eschar, thus free-range larvae were used because they can move beneath the hard necrotic tissue and dissolve it. [source] Ischaemia: another possible cause of yet another entityCOLORECTAL DISEASE, Issue 7 2007Najib Haboubi No abstract is available for this article. [source] Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at-risk myocardium: an experimental study in the pigACTA PHYSIOLOGICA, Issue 1 2010A. Waldenström Abstract Aim:, ,Pre-treatment' with short repetitive periods of ischaemia (ischaemic preconditioning) has proved to be a powerful mechanism for modification of the extent of myocardial damage following acute coronary artery occlusion. The exact mechanism of protection induced by ischaemic preconditioning is not known. We herewith put forward a contributing component for protection with preconditioning involving a shift in the adenylate kinase (AK) equilibrium reaction in favour of adenosine triphosphate (ATP) formation. Methods:, A coronary artery was occluded in anaesthetized thoracotomized pigs to induce ischaemic preconditioning as well as a longer period of ischaemia. Microdialysis probes were inserted in ischaemic and control myocardium and were infused with 14C- adenosine with two different specific activities. 14C-lactate was identified and measured in the effluent. Results:,14C-adenosine was taken up by non-preconditioned and preconditioned myocardium during ischaemia. Significantly increased levels of 14C-lactate were recovered in preconditioned myocardium. 14C-adenosine with high specific activity resulted in a specific activity of lactate that was 2.7 times higher than that of lactate after administration of 14C-adenosine with low specific activity. Mass spectrography verified the identity of 14C-lactate. Conclusions:, Preconditioning up-regulates a new metabolic pathway (starting with 5,-nucleotidase and ending up with lactate) resulting in ATP formation in the micromolar range on top of another effect terminating in a useful shift in the AK equilibrium reaction in favour of ATP generation in the millimolar range. Although the up-regulation of the purine nucleoside phosphorylase pathway is clearly demonstrated, its biological relevance remains to be proved. [source] A role for the volume regulated anion channel in volume regulation in the murine CNS cell line, CADACTA PHYSIOLOGICA, Issue 2 2010V. L. Harvey Abstract Aim:, The role of the volume regulated anion channel (VRAC) in a model CNS neuronal cell line, CAD, was investigated. Methods:, Changes in cell volume following hypotonic challenges were measured using a video-imaging technique. The effect of the Cl, channel antagonists tamoxifen (10 ,m) and 4,4,-diisothiocyanatostilbene-2,2,-disulphonic acid (DIDS; 100 ,m) on regulatory volume decrease (RVD) were measured. The whole-cell voltage-clamp technique was used to characterize IClswell, the current underlying the VRAC. Results:, Using the video-imaging technique, CAD cells were found to swell and subsequently exhibit RVD when subjected to a sustained hypotonic challenge from 300 mOsmol kg,1 H2O to 210 mOsmol kg,1 H2O. In the presence of tamoxifen (10 ,m) or DIDS (100 ,m) RVD was abolished, suggesting a role for the VRAC. A hypotonic solution (230 mOsmol kg,1 H2O) evoked IClswell, an outwardly rectifying current displaying time-independent activation, which reversed upon return to isotonic conditions. The reversal potential (Erev) for IClswell was ,14.7 ± 1.4 mV, similar to the theoretical Erev for a selective Cl, conductance. IClswell was inhibited in the presence of DIDS (100 ,m) and tamoxifen (10 ,m), the DIDS inhibition being voltage dependent. Conclusions:, Osmotic swelling elicits an outwardly rectifying Cl, conductance in CAD cells. The IClswell observed in these cells is similar to that observed in other cells, and is likely to provide a pathway for the loss of Cl, which leads to water loss and RVD. As ischaemia, brain trauma, hypoxia and other brain pathologies can cause cell swelling, CAD cells represent a model cell line for the study of neuronal cell volume regulation. [source] Cardioprotection of bradykinin at reperfusion involves transactivation of the epidermal growth factor receptor via matrix metalloproteinase-8ACTA PHYSIOLOGICA, Issue 4 2009C. Methner Abstract Aim:, The endogenous autacoid bradykinin (BK) reportedly reduces myocardial infarct size when given exogenously at reperfusion. Muscarinic and opioid G-protein-coupled receptors are equally protective and have been shown to couple through a matrix metalloproteinase (MMP)-dependent transactivation of the epidermal growth factor receptor (EGFR). Here we test whether BK protects the rat heart through the EGFR by an MMP-dependent pathway. Methods:, Infarct size was measured in isolated perfused rat hearts undergoing 30 min regional ischaemia followed by 120 min reperfusion. In additional studies HL-1 cardiomyocytes were loaded with tetramethylrhodamine ethyl to measure their mitochondrial membrane potential (,m). Adding the calcium ionophore calcimycin, causes ,m-collapse presumably due to calcium-induced mitochondrial permeability transition. Results:, As expected, BK (100 nmol L,1) started 5 min prior to reperfusion reduced infarct size from 38.9 ± 2.0% of the ischaemic zone in control hearts to 22.2 ± 3.3% (P < 0.001). Co-infusing the EGFR inhibitor AG1478, the broad-spectrum MMP-inhibitor GM6001, or a highly selective MMP-8 inhibitor abolished BK's protection, thus suggesting an MMP-8-dependent EGFR transactivation in the signalling. Eighty minutes of exposure to calcimycin reduced the mean cell fluorescence to 37.4 ± 1.8% of untreated cells while BK could partly preserve the fluorescence and, hence, protect the cells (50.5 ± 2.3%, P < 0.001). The BK-induced mitochondrial protection could again be blocked by AG1478, GM6001 and MMP-8 inhibitor. Finally, Western blotting revealed that BK's protection was correlated with increased phosphorylation of EGFR and its downstream target Akt. Conclusion:, These results indicate that BK at reperfusion triggers its protective signalling pathway through MMP-8-dependent transactivation of the EGFR. [source] Post-ischaemic activation of kinases in the pre-conditioning-like cardioprotective effect of the platelet-activating factorACTA PHYSIOLOGICA, Issue 3 2009C. Penna Abstract Aim:, Platelet-activating factor (PAF) triggers cardiac pre-conditioning against ischemia/reperfusion injury. The actual protection of ischaemic pre-conditioning occurs in the reperfusion phase. Therefore, we studied in this phase the kinases involved in PAF-induced pre-conditioning. Methods:, Langendorff-perfused rat hearts underwent 30 min of ischaemia and 2 h of reperfusion (group 1, control). Before ischaemia, group 2 hearts were perfused for 19 min with PAF (2 × 10,11 m); groups 3,5 hearts were co-infused during the initial 20 min of reperfusion, with the protein kinase C (PKC) inhibitor chelerythrine (5 × 10,6 m) or the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (5 × 10,5 m) and atractyloside (2 × 10,5 m), a mitochondrial permeability transition pore (mPTP) opener respectively. Phosphorylation of PKC,, PKB/A,t, GSK-3, and ERK1/2 at the beginning of reperfusion was also checked. Left ventricular pressure and infarct size were determined. Results:, PAF pre-treatment reduced infarct size (33 ± 4% vs. 64 ± 5% of the area at risk of control hearts) and improved pressure recovery. PAF pre-treatment enhanced the phosphorylation/activation of PKC,, PKB/A,t and the phosphorylation/inactivation of GSK-3, at reperfusion. Effects on ERK1/2 phosphorylation were not consistent. Infarct-sparing effect and post-ischaemic functional improvement induced by PAF pre-treatment were abolished by post-ischaemic infusion of either chelerythrine, LY294002 or atractyloside. Conclusions:, The cardioprotective effect exerted by PAF pre-treatment involves activation of PKC and PI3K in post-ischaemic phases and might be mediated by the prevention of mPTP opening in reperfusion via GSK-3, inactivation. [source] AMP-activated protein kinase: a core signalling pathway in the heartACTA PHYSIOLOGICA, Issue 1 2009A. S. Kim Abstract Over the past decade, AMP-activated protein kinase (AMPK) has emerged as an important intracellular signalling pathway in the heart. Activated AMPK stimulates the production of ATP by regulating key steps in both glucose and fatty acid metabolism. It has an inhibitory effect on cardiac protein synthesis. AMPK also interacts with additional intracellular signalling pathways in a coordinated network that modulates essential cellular processes in the heart. Evidence is accumulating that AMPK may protect the heart from ischaemic injury and limit the development of cardiac myocyte hypertrophy to various stimuli. Heart AMPK is activated by hormones, cytokines and oral hypoglycaemic drugs that are used in the treatment of type 2 diabetes. The tumour suppressor LKB1 is the major regulator of AMPK activity, but additional upstream kinases and protein phosphatases also contribute. Mutations in the regulatory ,2 subunit of AMPK lead to an inherited syndrome of hypertrophic cardiomyopathy and ventricular pre-excitation, which appears to be due to intracellular glycogen accumulation. Future research promises to elucidate the molecular mechanisms responsible for AMPK activation, novel downstream AMPK targets, and the therapeutic potential of targeting AMPK for the prevention and treatment of myocardial ischaemia or cardiac hypertrophy. [source] Pretreatment with insulin before ischaemia reduces infarct size in Langendorff-perfused rat heartsACTA PHYSIOLOGICA, Issue 2 2009B. N. Fuglesteg Abstract Aim:, To compare the possible role of Akt and mammalian target of rapamycin (mTOR) in mediating cardioprotection against ischaemia under three different conditions: (1) During ischaemic preconditioning (IPC), (2) when insulin was given as a pretreatment agent (InsPC) and (3) when insulin was given as a reperfusion cell survival agent (InsR). Methods:, Isolated perfused rat hearts were subjected to IPC (3 × 5 min) or InsPC (50 mU mL,1; 3 × 5 min), before 30 min of regional ischaemia followed by 120 min of reperfusion ± 1L-6-hydroxymethyl- chiro -inositol-2 - [(R)-2- O -methyl-3- O -octadecylcarbonate] (HIMO) (20 ,m; Akt inhibitor) or rapamycin (1 nm; mTOR inhibitor). In addition, insulin (3 mU mL,1) was given at the onset of reperfusion, ±HIMO or rapamycin. Risk zone (R) and infarct size (I) were determined with Evans blue and tetrazolium staining respectively. Western blot analysis was performed on tissue from Langendorff-perfused rat hearts and cell lysates from cultured HL1 cells. Results:, IPC, InsPC and InsR treatment resulted in a significant reduction in infarct size compared to controls (all P < 0.05). This protective effect of IPC and insulin was abolished by the inhibitors. However, the putative Akt inhibitor, although capable of abolishing cardioprotection induced by insulin, was not able to inhibit insulin-induced phosphorylation of Akt in Langendorff-perfused rat hearts and cultured HL1 cells. The target for this compound therefore remains to be determined. Conclusion:, IPC and insulin (either as InsPC or InsR) appear to activate mTOR, and this kinase seems to play an essential role in cardioprotection against ischaemia and reperfusion injury as rapamycin blocked the protection. [source] Measuring diffusion parameters in the brain: comparing the real-time iontophoretic method and diffusion-weighted magnetic resonanceACTA PHYSIOLOGICA, Issue 1 2009I. Vorisek Abstract The extracellular space (ECS) diffusion parameters influence the movement of ions, neuroactive substances, hormones and metabolites in the nervous tissue. They also affect extrasynaptic transmission, a mode of signal transmission dependent solely on diffusion. This review compares in detail two methods for studying diffusion in the brain: the real-time iontophoretic tetramethylammonium method for ECS volume fraction and tortuosity measurements and diffusion weighted-magnetic resonance imaging for measuring the apparent diffusion coefficient of water. The results obtained using both methods under physiological conditions (post-natal development, ageing) or in pathologies (brain injury, ischaemia) and their similarities and differences are discussed. [source] Reduced calcium tolerance in rat cardiomyocytes after myocardial infarctionACTA PHYSIOLOGICA, Issue 4 2002I. Sjaastad ABSTRACT During ischaemia and reperfusion the intracellular Na+ concentration is elevated in the cardiomyocytes and the cells are depolarized, both favouring reverse mode Na,Ca-exchange loading of the cell with Ca2+. We examined whether cardiomyocytes from rats with congestive heart failure (CHF) and younger rats (HINCX) which both have a high expression of the Na,Ca-exchanger protein (NCX) showed reduced tolerance to extracellular Ca2+. The CHF was induced in Isofluran anaesthetized rats by left coronary artery ligation. Isolated cardiomyocytes were loaded with Fura-2AM and 140 mm Na+ and exposed to 0.05 mm Ca2+. Expression of the Na,Ca-exchanger protein was analysed. Fura-2 340/380 ratio rose more rapidly in HINCX and CHF than in SHAM, and the rise was abolished by Ni2+. Hypercontracture developed more frequently in HINCX and CHF than in SHAM cells. The amount of NCX was 54% higher in HINCX and 76% higher in CHF compared with SHAM. Na+ -loaded cardiomyocytes from CHF and HINCX rats are more susceptible to Ca2+ overload than SHAM cells because of the increased capacity for Na,Ca-exchange. [source] Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated heartsACTA PHYSIOLOGICA, Issue 4 2002P. Tähepõld ABSTRACT Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia,reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose,response to phenylephrine (PHE), prostaglandin F2, (PGF2,) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 ± 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 ± 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application. [source] Glutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stressACTA PHYSIOLOGICA, Issue 1 2001S. Leichtweis The efficacy of glutathione (GSH) in protecting ischaemia-reperfusion (I-R) induced cardiac dysfunction and myocardial oxidative stress was studied in open-chest, stunned rat heart model. Female Sprague,Dawley rats were randomly divided into three experimental groups: (1) GSH-depletion, by injection of buthionine sulphoxamine (BSO, 4 mmol kg,1, i.p.) 24 h prior to I-R, (2) BSO injection (4 mmol kg,1, i.p.) in conjunction with acivicin (AT125, 0.05 mmol kg,1, i.v.) infusion 1 h prior to I-R, and (3) control (C), receiving saline treatment. Each group was further divided into I-R, with surgical occlusion of the main left coronary artery (LCA) for 30 min followed by 20 min reperfusion, and sham. Myocardial GSH content and GSH : glutathione disulphide (GSSG) ratio were decreased by ,50% (P < 0.01) in both BSO and BSO + AT125 vs. C. Ischaemia-reperfusion suppressed GSH in both left and right ventricles of C (P < 0.01) and left ventricles of BSO and BSO + AT125 (P < 0.05). Contractility (+dP/dt and ,dP/dt) in C heart decreased 55% (P < 0.01) after I and recovered 90% after I-R, whereas ±dP/dt in BSO decreased 57% (P < 0.01) with ischaemia and recovered 76 and 84% (P < 0.05), respectively, after I-R. For BSO + AT125, ±dP/dt were 64 and 76% (P < 0.01) lower after ischaemia, and recovered only 67 and 61% (P < 0.01) after I-R. Left ventricular systolic pressure in C, BSO and BSO + AT125 reached 95 (P > 0.05) 87 and 82% (P < 0.05) of their respective sham values after I-R. Rate-pressure double product was 11% (P > 0.05) and 25% (P < 0.05) lower in BSO and BSO + AT125, compared with Saline, respectively. BSO and BSO + AT125 rats demonstrated significantly lower liver GSH and heart Mn superoxide dismutase activity than C rats after I-R. These data indicate that GSH depletion by inhibition of its synthesis and transport can exacerbate cardiac dysfunction inflicted by in vivo I-R. Part of the aetiology may involve impaired myocardial antioxidant defenses and whole-body GSH homeostasis. [source] Sturge,Weber syndrome and paroxysmal hemiparesis: epilepsy or ischaemia?DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 11 2004Floor E Jansen MD Transient neurological deficits experienced by patients with Sturge,Weber syndrome can be caused by epilepsy, or may result from temporary ischaemia of the cortex underlying the vascular malformation. To show the difficulty in distinguishing seizures from ischaemic symptoms, two male children with episodes of acute unilateral weakness are presented here as well as a review of the literature. The first child presented at 2 years of age with a sudden increase in his pre-existing right hemiparesis accompanied by screaming. Ictal epileptiform activity was recorded at the moment of the attack, and subsequent seizures were controlled by adjustment of antiepileptic drug treatment. The second child presented at 4 years of age with attacks of vomiting and a coinciding increase in the pre-existing paresis of the left leg. Electroencephalogram (EEG) recording did not show ictal epileptiform activity. The origin was presumed to be vascular. Treatment with aspirin led to control of these transient ischaemic attacks. Ictal EEG is needed to differentiate between an epileptic and an ischaemic origin of transient focal deficit. Treatment with aspirin should be considered if an ischaemic origin cannot be excluded. [source] | |||||||||||||||||||||||||||||||||||||||||||