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

Male Sprague Dawley rats were anesthetised with Xylazine and Ketamine intraperitoneally. After a lateral craniotomy the cerebral inferior vein was ligated and a very small clip (Biemer clip) was placed on the MCA near its origin for 1 hour. This procedure induced a focal infarction in 100% of the rats. After removal of the clip the lumen of the MCA was patent. The study was divided in 3 randomized groups (control group n = 15; Nimodipine group n = 11, treatment 30 micrograms/hour/kg body-weight; Mannitol group n = 15, treatment 5.4 ml/hour/kg body-weight). Besides heart-rate, ECG and blood pressure we measured the extracellular potassium and calcium concentration with ion-selective microelectrodes; the ICBF was estimated by laser-doppler-flowmeter. The MCA was clipped for 1 hour. After 1 hour of reperfusion the brain was fixated and the volume of infarction was measured by serial slices. Nimodipine or Mannitol treatment started 5 min before clipping the MCA. In rats with Nimodipine treatment the extracellular calcium starts at a significantly higher level (2.3 +/- 0.5 mmol/l) and the decrease during ischemia remains above a level of 1.2 +/- 0.2 mmol/l. The increase in potassium during ischemia and Nimodipine (calculated in change of concentration/time [dc/dt]) is significantly slower than in the control group. In contrast to the post-ischemic hyper- and hypoperfusion in the control group the reperfusion in the Mannitol group is nearly normal. In the control group the infarction volume is 20% of the brain, in the Nimodipine group 15% and in the Mannitol group only 11%. The calcium antagonist Nimodipine and the free-radical scavenger Mannitol therefore promise to be a way to treat or prevent temporary focal cerebral ischemia.
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PMID:The effect of mannitol and nimodipine treatment in a rat model of temporary focal ischemia. 838 44

We studied the recovery of retinal pigment epithelium and retinal function after 80 minutes of pressure-induced ischemia in rabbits. Just before restoring circulation, we gave intravenous mannitol (an osmotic agent and free-radical scavenger), dextromethorphan (an N-methyl-D-aspartate receptor antagonist), or catalase (an antioxidant enzyme). Mannitol has not previously been shown to be protective for retinal or retinal pigment epithelial ischemia. At 24 hours after reperfusion, the electroretinogram b-wave was reduced to 37% of preischemic amplitude in untreated eyes, but it recovered to 67% to 80% after treatment with all three agents. The c-wave was replaced by a negative slow PIII response in control eyes and in seven of 12 catalase-treated eyes, but it recovered by 58% to 82% in the remaining catalase-treated eyes and all the mannitol- and dextromethorphan-treated eyes. Histologic examination confirmed that retinal pigment epithelium as well as retina had been damaged by the ischemia. The effects of mannitol seem of special interest, since the drug has a dual mechanism of action and is clinically available.
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PMID:Mannitol, dextromethorphan, and catalase minimize ischemic damage to retinal pigment epithelium and retina. 844 53

In our miniature swine model of brain retraction ischemia under conditions simulating the neurosurgical operating room, we studied the effects of bolus mannitol (2 g/kg) administration on cerebral blood flow, blood pressure, blood viscosity, hematocrit, sodium, and potassium serially for 4 hours following administration, at which time a second bolus was administered. Both viscosity and hematocrit were significantly decreased transiently following both the first and second boluses. Sodium was decreased for 30 minutes following the first bolus, 15 minutes following the second bolus, and increased at 150 minutes and later following the second bolus. There was a mild decrease in blood pressure and a mild increase in cerebral blood flow following mannitol, but little difference between the first hour following a bolus (when the viscosity and hematocrit were decreased) and hours 2-4 (when they were near baseline). Mannitol's effects on blood pressure and cerebral blood flow probably depend on factors in addition to its effects on blood viscosity and hematocrit. The results are discussed in light of previous findings that bolus mannitol administration may improve cerebral blood flow in ischemia, but does not appear to benefit the preservation of brain electrical activity.
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PMID:Effects of mannitol on cerebral blood flow, blood pressure, blood viscosity, hematocrit, sodium, and potassium. 845 86

Monitoring of brain tissue partial pressure of O2 (ti-pO2) is a promising new technique that allows early detection of impending cerebral ischemia in brain-injured patients. The purpose of this study was to investigate the effects of standard therapeutic interventions used in the treatment of intracranial hypertension in comatose patients on cerebral oxygenation. In the neurosurgical intensive care unit ti-pO2, arterial blood pressure, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and jugular bulb oxygen saturation (SjvO2) were prospectively studied (0.1 Hz acquisition rate) in 23 comatose patients (21 with severe traumatic brain injury, 2 with intracerebral hematoma) during various treatment modalities: elevation of CPP with dopamine (n = 35), lowering of the head (n = 22), induced arterial hypocapnia (n = 13), mannitol infusion (n = 16), and decompressive craniotomy (n = 1). Ischemic episodes ('IE' = ti-pO2 < 10 mmHg for > 15 min) within the first week after the insult were always associated with unfavorable neurological outcome. Elevation of CPP from 32 +/- 2 to 67 +/- 4 mmHg significantly improved ti-pO2 by 62% (13 +/- 2 to 21 +/- 1 mmHg) and reduced ICP indicating intact cerebral autoregulation. Further raising CPP from 68 +/- 2 to 84 +/- 2 mmHg did not alter ti-pO2. Mannitol-induced ICP reduction from 23 +/- 1 to 16 +/- 2 mmHg did not affect ti-pO2, nor did lowering of the head from 30 degrees to 0 degree. Hyperventilation from an endtidal pCO2 of 29 +/- 3 to 21 +/- 3 mmHg normalized ICP and CPP, but significantly reduced ti-pO2 from 31 +/- 2 to 14 +/- 3 mmHg. Decompressive craniotomy in a 15-year old patient with refractory intracranial hypertension instantly restored ti-pO2. Based on the present data, our understanding of many interventions previously believed to improve brain oxygenation might have to be re-evaluated. A CPP > 60 mmHg emerges as the most important factor determining sufficient brain tissue pO2. Any intervention used to further elevate CPP does not improve ti-pO2, to the contrary, hyperventilation even bears the risk of inducing brain ischemia.
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PMID:Brain tissue pO2-monitoring in comatose patients: implications for therapy. 919 72

Intracranial hypertension leading to brain stem herniation is a major cause of death in fulminant hepatic failure (FHF). Mannitol, barbiturates, and hyperventilation have been used to treat brain swelling, but most patients are either refractory to medical management or cannot be treated because of concurrent medical problems or side effects. In this study, we examined whether allogeneic hepatocellular transplantation may prevent development of intracranial hypertension in pigs with experimentally induced liver failure. Of the two preparations tested--total hepatectomy (n = 47), and liver devascularization (n = 16)--only pigs with liver ischemia developed brain edema provided, however, that animals were maintained normothermic throughout the postoperative period. This model was then used in transplantation studies, in which six pigs received intrasplenic injection of allogeneic hepatocytes (2.5 x 10(9) cells/pig) and 3 days later acute liver failure was induced. In both models (anhepatic state, liver devascularization), pigs allowed to become hypothermic had significantly longer survival compared to those maintained normothermic. Normothermic pigs with liver ischemia had, at all time points studied, ICP greater than 20 mmHg. Pigs that received hepatocellular transplants had ICP below 15 mmHg until death; at the same time, cerebral perfusion pressure (CPP) in transplanted pigs was consistently higher than in controls (45 +/- 11 mmHg vs. 16 +/- 18 mmHg; p < 0.05). Spleens of transplanted pigs contained clusters of viable hepatocytes (hematoxylin-eosin, CAM 5.2). It was concluded that removal of the liver does not result in intracranial hypertension; hypothermia prolongs survival time in both anhepatic pigs and pigs with liver devascularization, and intrasplenic transplantation of allogeneic hepatocytes prevents development of intracranial hypertension in pigs with acute ischemic liver failure.
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PMID:Transplantation of hepatocytes for prevention of intracranial hypertension in pigs with ischemic liver failure. 971 Mar 4

The purpose of this study was to determine whether the loop diuretics furosemide, bumetanide and ethacrynic acid, which block the KCC1 potassium-chloride transporter in the kidney loop of Henle and the KCC2 potassium-chloride transporter in neuronal membranes, would prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. The rats were infused with the test agent via tail vein shortly before being tested for seizure susceptibility by exposure to loud noise (an alarm bell) for 60 s. Sound exposures were repeated at intervals to determine the time course of the seizure suppression effect. All three loop diuretics suppressed sound-triggered seizures in post-ischemic rats tested 2 days to 4 weeks after the ischemic exposure. Furosemide 200 mg/kg had no effect in 4/4 rats made acutely audiogenic seizure-prone by infusion of bicuculline into the inferior colliculus, indicating that the effect was not due to general anti-seizure activity. Mannitol 2 g/kg had no effect in 6/6 post-ischemic rats, indicating that the effect was not due to diuresis or fluid shifts. These results are consistent with the hypothesis that the exposure to global ischemia caused an upregulation of the potassium-chloride transporter KCC2 in neurons which persisted for at least 4 weeks.
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PMID:Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. 1079 96

This review evaluates the various causes and management of acute renal failure (ARF) in children. ARF is defined as an abrupt decline in the renal regulation of water, electrolytes and acid-base balance, and continues to be an important factor contributing to the morbidity and mortality of critically ill infants and children. The common causes of ARF in children include acute tubular necrosis secondary to various causes (including congestive heart failure and sepsis), haemolytic uremic syndrome, and glomerulonephritis and urinary tract obstruction. Ischaemia, toxins (including drugs) as well as primary parenchymal disease, have to be considered and ARF can also be a complication of systemic disease. The basic principles of management are avoidance of life-threatening complications, maintenance of fluid and electrolyte balance, and nutritional support. Only a few patients require specific management of the underlying disorder, although it is important to diagnose these conditions. Knowledge about the use of drugs for the prevention of ARF is scarce. Mannitol, low-dose dopamine, calcium channel antagonists, atrial natriuretic peptide and albumin have been evaluated and, where possible, meta-analyses are cited. Mannitol treatment appears to be warranted prophylactically after paediatric renal transplantation. Albumin infusion can reverse prerenal ARF in children with nephritic syndrome. For treatment of the complications of hyperkalaemia and volume overload, salbutamol, insulin and glucose infusion and diuretics such as furosemide and sodium bicarbonate, are discussed. All of the major dialysis modalities (peritoneal dialysis, haemodialysis and continuous haemofiltration) can be used to provide equivalent solute clearance and ultrafiltration. The indication for, and the choice of the modality depend on the patient requirements and on local resources, and should involve the care of a paediatric nephrologist. Peritoneal dialysis requires minimal equipment and infrastructure, is easy to perform and remains the favoured modality of renal replacement therapy in children. However, continuous haemofiltration is an excellent alternative to peritoneal dialysis in patients with ARF and severe fluid overload. Dialysis remains the most important tool to bridge the time needed for recovery of renal function. There is increasing evidence that more intense use of dialysis may improve the overall prognosis.
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PMID:Acute renal failure in children: aetiology and management. 1173 64

We had previously studied different modes of prevention of liver ischemia-reperfusion (IR)-induced remote organ reperfusion injury, a challenge that remains partly unmet. We have now studied the capability of mannitol at different doses in abrogating liver IR-induced lung reperfusion injury in an isolated double-organ model. Rat livers ( n = 8/group) were perfused with Krebs-Henseleit solution (control) or made globally ischemic (IR) for 2 h, after which they were paired with normal lungs and "reperfused" together for 15 min. The lungs were then perfused alone with the accumulated Krebs for an additional 45 min. Another 4 control and 4 IR pairs were reperfused with Krebs containing mannitol at.22 mmol,.55 mmol,.77 mmol, or 1.1 mmol. Mannitol.22 mmol and 1.1 mmol failed to attenuate IR-lung injury as indicated by 50-95% increases in inspiratory and perfusion pressures and compliance reduction, a 70% increase in weight gain, and a 2-50-fold increase in bronchoalveolar lavage volume and content. Mannitol.55 mmol prevented all these abnormalities, and.77 mmol attenuated only changes in ventilatory parameters. The latter two treatments were also associated with a 50% reduction in xanthine oxidase activity and a 35-45% increase in the reduced glutathione tissue content compared with the nontreated IR-paired lungs. It is concluded that mannitol in a narrow therapeutic dose range can reduce oxidalive stress-induced lung damage that is related to liver IR.
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PMID:Mannitol dose-dependently attenuates lung reperfusion injury following liver ischemia reperfusion: a dose-response study in an isolated perfused double-organ model. 1264 34

The temporary occlusion of cerebral vessels is being used with increased frequency in the surgical management of cerebral vascular disease, and this procedure places brain tissue at risk of infarction. Using a modified version of a well-established model of focal cerebral ischemia in the rabbit, we tested the protective effect of a combination of six agents; each agent was selected to temporarily block one or more neuronal functions, hence reducing their metabolic demands. The combination of six agents had been previously shown to protect neurological function against ischemia. Ten male adult New Zealand White rabbits were anesthetized with halothane, and physiological parameters were maintained within normal ranges. A branch of the left external carotid artery was catheterized and the vasculature supplying the left middle cerebral artery (MCA) territory was isolated. Mannitol was infused via the external carotid artery into the left internal carotid artery to open the blood-brain barrier in the territory of the MCA. This infusion was followed by either Ames' medium alone (control) or Ames' medium containing the combination of agents: tetrodotoxin (0.1 micromol/L), 2-amino-4-phosphonobutyric acid (20 mumol/L), 2-amino-5-phosphonovaleric acid (1 mmol/L), amiloride (1 mmol/L), magnesium (10 mmol/L), and lithium (10 mmol/L). Ischemia in the left MCA territory was then induced for 2 hours, followed by 4 hours of reperfusion. Animals pretreated with the combination of agents sustained infarctions that were markedly smaller (mean+/-SEM, 46+/-19.7 mm(3), n=5) than control animals (300+/-46.5 mm(3), n=5, P<.001). We conclude that the strategy of locally delivering a combination of agents designed to temporarily reduce neuronal metabolic demands by temporarily blocking several nonvital neuronal functions, can reduce the infarction induced by a focal reduction in cerebral blood flow in the rabbit.
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PMID:Avoiding stroke during cerebral arterial occlusion by temporarily blocking neuronal functions in the rabbit. 1789 3

Optical coherence tomography (OCT) is a rapidly emerging imaging modality that can provide non-invasive, cross-sectional, high-resolution images of tissue morphology in situ and in real-time. In the present series of studies, we used a high-speed OCT imaging system equipped with a frequency-swept laser light source (1.3 mum wavelength) to study living kidneys in situ. Adult, male Munich-Wistar rats were anesthetized, a laparotomy was performed and the living kidneys were exposed for in situ observation. We observed the kidneys prior to, during and following exposure to renal ischemia induced by clamping the renal artery. The effects of intravenous mannitol infusion (1.0 ml of 25%) prior to and during renal ischemia were also studied. Finally, living kidneys were flushed with a renal preservation solution, excised and observed while being stored at 0-4 degrees C. Three-dimensional OCT data sets enabled visualization of the morphology of the uriniferous tubules and the renal corpuscles. When renal ischemia was induced, OCT revealed dramatic shrinkage of tubular lumens due to swelling of the lining epithelium. Three-dimensional visualization and volumetric rendering software provided an accurate evaluation of volumetric changes in tubular lumens in response to renal ischemia. Observations of kidneys flushed with a renal preservation solution and stored at 0-4 degrees C also revealed progressive and significant loss of tubular integrity over time. Intravenous infusion of mannitol solution resulted in thinning of the tubular walls and an increase in the tubular lumen diameters. Mannitol infusion also prevented the cell swelling that otherwise resulted in shrinkage of proximal tubule lumens during ischemia. We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the living kidney in a non-invasive fashion. Possible clinical applications are discussed.
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PMID:High-resolution optical coherence tomography imaging of the living kidney. 1826 76


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