Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of pretreatment with a potent platelet-activating factor (PAF) receptor antagonist (E5880) on the changes in hepatic and systemic metabolism induced by transient hepatic ischemia and reperfusion. Sixty-five rabbits were assigned to four groups that either did or did not undergo a period of hepatic ischemia and reperfusion with or without pretreatment. E5880 was administered intraportally 1 minute prior to inflow occlusion. Twenty minutes of warm ischemia was followed by 30 minutes of reperfusion. Blood gas analyses and measurements of levels of arterial pyruvate, lactate, and ketone bodies, arterial and portal ammonia and endotoxin, and intrahepatic adenine nucleotide, pyruvate, and lactate were performed. Results were analyzed by either ANOVA or chi-square analysis. Hepatic tissue ATP and energy charge levels were significantly increased and the AMP level was significantly decreased after 30 minutes of reperfusion in the pretreatment group compared to those without pretreatment. At the same time, parameters reflecting hepatic mitochondrial function, such as the arterial ketone body ratio and arterial ammonia level, improved, although they were not statistically significant. No difference was observed for parameters reflecting systemic changes, such as arterial blood gas values and pyruvate and lactate levels. PAF is thought to mediate metabolic changes after hepatic ischemia and reperfusion. PAF released in the liver may exert local effects, which appear to be attenuated by pretreatment with E5880. Systemic metabolic changes seen after hepatic ischemia and reperfusion may be mediated by factors other than PAF.
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PMID:Effects of platelet-activating factor antagonist E5880 on intrahepatic and systemic metabolic responses to transient hepatic inflow occlusion and reperfusion in the rabbit. 879 65

Tissue damage in ischemia/reperfusion injury may be mediated by oxidative stress caused by reactive oxidant species. Since such reactive species are difficult to measure directly, changes in antioxidant concentrations are often used as an indication of oxidative stress. In this study, microdialysis membranes were inserted into the livers of anesthetized rats to determine the effects of ischemia/reperfusion on the extra-cellular concentrations of two antioxidants, uric acid and ascorbic acid. Total hepatic ischemia was induced for 30 min by clamping the portal triad and was followed by 60 min of reperfusion. Uric acid and ascorbic acid concentrations were measured in microdialysis perfusates by high-performance liquid chromatography with electrochemical detection. Initial uric acid and ascorbic acid concentrations were high after insertion of membranes into the liver and decreased rapidly within 90 min (P < 0.001; ANOVA with repeated measures). Uric acid concentrations increased over 300% after ischemia and by 600% during the first 30 min of reperfusion (n = 8; P < 0.05). Ascorbic acid concentrations were 60% higher than controls after ischemia and 90% higher during the first 30 min of reperfusion (n = 8; P < 0.05). Alterations in concentrations of these redox-active molecules may be associated with oxidative stress in liver extracellular fluid during ischemia/reperfusion.
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PMID:Ischemia/reperfusion alters uric acid and ascorbic acid levels in liver. 880 65

Preliminary studies on ischemia/reperfusion injury in transplanted small bowel grafts showed that secretory phospholipase A2 (sPLA2) may play a substantial role by breaking down membrane phospholipids. This study sought to determine the normal values of sPLA2 in the rat small bowel as a function of site and length as a baseline for future studies. The entire small bowel of male Lewis rats (200 g) was flushed with normal saline to eliminate solid contents. In group 1, the entire small bowel was divided into 5-cm segments (numbered 1-9), which were snap frozen and processed the same day for sPLA2. In group 2, a 25-cm segment of bowel (corresponding to segments 2-6 in group 1) was harvested from each animal, snap frozen, and immediately processed for sPLA2. To assess the effect of bowel storage on enzyme content, group 3 and group 4 grafts were stored for 7 and 14 days, respectively, at -85 degrees C prior to processing. All samples were homogenized in buffer, extracted with H2SO4 and assayed for sPLA2 activity using [1-14C]oleate-labeled autoclaved Escherichia coli as substrate. Results were analyzed statistically by ANOVA. sPLA2 activity rose from 85.46 +/- 14.46% hydrolysis/min fraction-1 in segment 1, to 476.38 +/- 176.75% hydrolysis/min fraction-1 in segment 9. The increase was linear and statistically significant (p < .0001). There was no significant difference in enzymatic activity between groups 2, 3, and 4. Group 2 activity was 263.02 +/- 43.74% hydrolysis/min fraction-1. This value was not statistically different from the mathematically calculated mean of segments 2-6 in group 1 (237.75). The results show that (1) sPLA2 activity increases predictably with distance from the ligament of Treitz (2) storage at -85 degrees C does not affect sPLA2, activity, and (3) 25-cm grafts may be evaluated in toto with reproducible baseline enzyme activity. Given the variability of enzyme activity along the course of the rat small bowel, it is imperative that exact location be identified in any studies evaluating sPLA2 activity.
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PMID:Secretory phospholipase A2 levels in rat small bowel. 888 69

Circulatory assist devices are used to treat patients awaiting cardiac transplantation to preserve life as well as to permit recovery of end-organ function. The efficacy of pulseless perfusion versus pulsatile perfusion in the recovery of end-organ function has not been fully determined. In this study, the efficacy of pulseless perfusion compared to pulsatile perfusion on the recovery of renal function after a 30 min period of normothermic ischemia was examined. Pigs were randomly assigned to four groups. In all groups, acute renal ischemia was induced by clamping both renal arteries for 30 min. Reperfusion for 120 min was performed using either pulsatile perfusion or pulseless perfusion at 65 +/- 1.6 mm Hg (Groups I [pulsatile] and II [pulseless]) and at 40 +/- 1.1 mm Hg (Groups III [pulsatile] and IV [pulseless]). After reperfusion, renal blood flow, hemodynamic power (pressure * flow: hemodynamic power), oxygen consumption (VO2), tissue ATP, and urine output (UO) in Groups I, II, and III were significantly higher than in Group IV (p < .01 by ANOVA). Histopathologic examinations were not significantly different between groups. Under hypotensive conditions, pulsatile perfusion improves hemodynamic power delivery to the organ compared to pulseless perfusion. These results suggest that a pulseless pump is acceptable as an assist device when normal flow or perfusion pressure is maintained.
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PMID:Effect of pulsatility and hemodynamic power on recovery of renal function. 894 75

Hypothermia has been reported to be beneficial in CNS physical injury and ischemia. We previously reported that posttraumatic cooling to 17 degrees C for 2 h increased survival of mouse spinal cord (SC) neurons subjected to physical injury (dendrite transection) but that cooling below 17 degrees C caused a lethal NMDA receptor-linked stress to both lesioned and uninjured neurons. The present study tested whether cooling below 17 degrees C increases extracellular levels of excitatory amino acids (EAA). SC cultures were placed at 10 degrees C or 37 degrees C. Glutamate (Glu) and aspartate (Asp) levels were higher in the medium of the cooled cultures after 0.5 h (23 +/- 4 nM/microgram vs. 4 +/- 1 nM/microgram and 4 +/- 1 nM/microgram vs. 1 +/- 0 nM/microgram, respectively). The concentration of each EAA then declined and reached a plateau at 2-4 h that was still significantly higher than control levels (p < 0.0001, two-factor ANOVA, three cultures per group). Other amino acids (glycine, asparagine, glutamine, serine) showed an opposite pattern, with higher levels in the 37 degrees C group. Both NMDA and non-NMDA antagonists prevented the lethal cold injury. Survival of SC neurons cooled at 10 degrees C for 2 h and rewarmed for 22 h was 58% +/- 25% in the control group, 94% +/- 5% in the CNQX-treated group, 97% +/- 5% in the DAPV-treated group, and 99% +/- 2% in the group treated with both antagonists [p < 0.0006, one factor ANOVA, five cultures (> 120 neurons) per group]. These results show that death of neurons cooled to 10 degrees C is caused by elevated extracellular Glu and Asp and requires activation of both the NMDA and non-NMDA receptor subtypes.
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PMID:The role of excitatory amino acids in hypothermic injury to mammalian spinal cord neurons. 900 66

We investigated whether moderate, transient whole-body hyperthermia (approximately 39.6 degrees C), if imposed 1 day following a brief episode of forebrain ischemia, would affect the neuropathologic outcome. Forty-two Wistar rats were subjected to either a 5- or 7-minute period of bilateral common carotid artery occlusion plus hypotension (50 mm Hg), or to the equivalent sham procedure. Twenty-four hours later, rats of one subgroup were placed into a hyperthermic chamber containing high-intensity lamps designed to elevate rectal temperature to 39 to 40 degrees C for 3 hours. Normothermic subgroups received the same procedures, but the heating lamps were turned off. Eight days after brain ischemia or the sham procedure, brains were perfusion-fixed, and numbers of ischemic-appearing CA1 pyramidal neurons were counted. In rats with 7-minute forebrain ischemia, delayed hyperthermia increased mean numbers of ischemic neurons by 2.6- to 2.7-fold in all subsectors of area CA1 (p < 0.05, ANOVA). Delayed hyperthermia in 5-minute ischemic rats also tended to increase mean numbers of ischemic neurons (by 11-fold in lateral, 6-fold in middle, and 5-fold in medial CA1 subsectors), but these differences were not statistically significant. We conclude that moderate, transient hyperthermia, even if occurring 1 day after a 7-minute global ischemic insult, exacerbates the extent of ischemic neuronal injury.
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PMID:Hyperthermia delayed by 24 hours aggravates neuronal damage in rat hippocampus following global ischemia. 906 63

Nitric oxide (NO) increases 3',5'-cyclic guanosine monophosphate (cGMP) in vascular smooth muscle and increases cerebral blood flow (CBF). In early stages of cerebral ischemia, NO plays a beneficial role in sustaining CBF. Subarachnoid hemorrhage (SAH), one of the main causes of ischemia, may impair vascular reactivity to NO. To test the hypothesis, 48 h after SAH was induced in rats, we examined the CBF response to the NO donor, SIN-1 (3-morpholinosydnonimine). We measured CBF by laser-Doppler flowmetry in association with: (1) intracarotid injection (for 30 min) of SIN-1 (1.5 mg/kg), 8-bromo-cGMP (7.5 mg/kg), papaverin (1.5 mg/kg) or vehicle; (2) cortical superfusion (for 90 min) of SIN-1 (10(-5) M) or vehicle through the cranial window. Hypotension produced by these vasodilators was controlled with phenylephrine. Vehicle alone did not change CBF throughout the measurement. Intracarotid infusion of SIN-1 (n = 6/group) increased CBF up to 128.6 +/- 3.9% and 111.9 +/- 2.9% in the control group and the SAH group, respectively. SAH significantly attenuated the response (P < 0.05, ANOVA). SAH did not affect the CBF increases elicited by intracarotid administration of cGMP or papaverin, or cortical superfusion of SIN-1. We conclude that during chronic vasospasm SAH disturbs the pathway between NO release and cGMP production in large cerebral arteries. The impairment accounts for the fragility of the brain in the face of ischemia following SAH.
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PMID:Subarachnoid hemorrhage impairs cerebral blood flow response to nitric oxide but not to cyclic GMP in large cerebral arteries. 920 Apr 92

Hemorrhage and resuscitation has been recognized as an exclusively destructive process which results in multiple organ dysfunction. Although it is well established that endogenous adaptation (preconditioning) mechanisms exist, it is unknown whether hemorrhage and resuscitation induces endogenous adaptive/protective mechanisms in the heart. Furthermore, alpha 1-adrenoceptors and nuclear factor kappa B (NF kappa B) have each been implicated in stress-induced signal transduction; however, whether they might be involved in hemorrhage-induced adaptive signal transduction remains unknown. This study tests the hypothesis that H/R activates myocardial NF kappa B and results in myocardial adaptation via alpha 1-adrenoceptors. Rats were briefly (10 min) hemorrhaged to 35 mmHg and resuscitated, sham operated, or neither, with and without prior alpha 1-adrenoceptor inhibition (prazosin). Hearts were then isolated and either probed for NF kappa B activation or subjected to a second insult consisting of global normothermic I/R (20 min/40 min). Antecedent hemorrhage and resuscitation activated myocardial NF kappa B and improved left ventricular developed pressure, coronary flow, and end diastolic pressure following ischemia-reperfusion (P < 0.05, ANOVA with Bonferroni-Dunn). Hemorrhage-induced adaptation was abolished by prior alpha 1-adrenoceptor blockade. This study constitutes the initial demonstration that H/R activates myocardial NF kappa B and induces adaptive signal transduction against ischemia-reperfusion injury.
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PMID:Alpha-adrenergic activation of myocardial NF kappa B during hemorrhage. 922 92

The ATP-sensitive K+ channel (K[ATP] channel) has been implicated in the mechanism of ischemic preconditioning. We compared the protective effects of ischemic preconditioning and a highly selective K(ATP) channel opener, BMS 180448, in human myocardium. BMS 180448 was either used alone or in combination with the K(ATP) channel blocker glibenclamide. Human atrial trabeculae derived from the right atrial appendage were suspended in an organ bath, superfused with oxygenated Tyrode's solution at 37degrees C, and paced at 1 Hz. Experimental groups (n = 6 in each) were as follows: (1) control (C)--90 minutes hypoxic substrate-free perfusion at 3 Hz (simulated ischemia), followed by 120 minutes of reoxygenation with substrate at 1 Hz (reperfusion); (2) preconditioning (PC)--3 minutes simulated ischemia, 7 minutes reperfusion, followed by 90 minutes simulated ischemia and 120 minutes reperfusion; (3) BMS 180448 (BMS)--exposure to the drug for 5 minutes prior to 90 minutes simulated ischemia and 120 minutes reperfusion; (4) BMS 180448 + glibenclamide (BMS + G)--glibenclamide exposure for 10 minutes, and BMS for 5 minutes prior to 90 minutes simulated ischemia and 120 minutes reperfusion. Force of contraction prior to the commencement of the protocol was assigned the arbitrary value of 100%. Percentage recovery of contractile function at 120 minutes reperfusion was used as the endpoint. BMS (59.2 +/- 8.6%) and preconditioning (50.5 +/- 3.6% ) produced a similar degree of recovery of function at the end of 120 minutes of reperfusion; this was significantly different from the untreated control group (20.8 +/- 3.5%, p < 0.05, ANOVA). When glibenclamide was added prior to BMS, protection was lost (20.5 +/- 2.7%). In this human atrial preparation, a highly selective K(ATP) channel opener mimicked the protective effect of ischemic preconditioning. This protective effect of BMS was abolished by glibenclamide. These findings confirm that the mechanism of ischemic preconditioning in human muscle may be mediated via opening of the K(ATP) channel.
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PMID:Comparison of the protective effects of a highly selective ATP-sensitive potassium channel opener and ischemic preconditioning in isolated human atrial muscle. 931 Feb 76

Mechanisms of injury in hepatic ischemia/reperfusion injury are poorly defined. Leukocytes are thought to be important in the final mechanism of hepatic damage. We intend to show the time course of abnormal leukocyte activity in the liver after ischemia/reperfusion (I/R) injury. Left lobar hepatic ischemia was induced for 20 min in anesthetized C57B1-6 mice. Measurements were taken at control, reperfusion, and matching sham times (no ischemia) of 2, 5, 12, and 24 h. Measurements were taken using rhodamine and fluorescein enhanced intravital microscopy. Post sinusoidal venules were evaluated for numbers of rolling leukocytes, leukocyte saltation, and leukocyte velocity. Data are expressed as number of rolling leukocytes per 100 microns venule length (2 min). Statistical analysis was by ANOVA. The number of rolling leukocytes at 5, 12, and 24 h of reperfusion (p < 0.001) was significantly higher than control and sham-operated animals. Leukocyte velocities were significantly slower in the 12 h I/R group when compared to sham animals (p < 0.001). These data show that there are definable and quantifiable changes in leukocyte kinetics in the liver after ischemia/reperfusion. These changes, which lasted for 24 h, are likely due to upregulation of various endothelial cell adhesion molecules. Delineation of these mechanisms may be important in disease states such as shock, sepsis, and hepatic transplantation.
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PMID:Hepatic ischemia/reperfusion affects leukocyte rolling and velocity. 936 52


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