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

Canine kidneys subjected to 90 min of warm ischemia (37 degrees C) were protected by the administration of methylprednisolone but not by furosemide or mannitol. There was no protective effect observed through the vasodilating or diuretic effect of furosemide in the ischemic canine kidney. Mannitol-induced diuresis before warm ischemia also did not prove to be beneficial for severely ischemic kidneys. Methylprednisolone (30 mg/kg) given 2 h prior to warm ischemia prevented irreversible kidney damage observed in the control and experimental groups. By day 8 the serum creatinine and creatinine clearance returned to normal levels.
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PMID:Study of the protective effect of methylprednisolone, furosemide, and mannitol on ischemically damaged kidneys. 38 34

Rats were anesthetized and their lift kidneys were made ischemic for 1 h by clamping of the aorta just above the left renal artery. Mannitol (2.5 g/kg), Dextran 70 (0.6 g/kg), methylprednisolone (50 and 100 mg/kg), and allopurinol (100 mg/kg body weight) were administered before, during, or after the ischemia period in order to test the effect of each of these drugs upon this model of renal injury. At 24 h after the release of the aortic clamp the left kidneys of the drug treated animals wwere perfusion fixed and processed for light and electron microscopy. Dextran administration to animals with ischemic kidneys gave rise to a pronounced vacuolization ("osmotic nephrosis"), in the entire proximal tubule and especially in the pars recta. This was in contrast to dextran administration to rats with nonischemic kidenys, which showed no or very mild "osmotic nephrosis." This demonstrates that ischemia makes rat kidneys more susceptible to the development of "osmotic nephrosis." In controls (no drug treatment) one hour of renal ischemia gave partial necrosis of pars recta of the proximal tubule, while the pars convoluta tubule survived. Mannitol treatment significantly reduced the amount of necrosis of the pars recta, whereas dextran, methylprednisolone, and allopurinol had no or a negative effect on the survival of the cells of the pars recta segment. It is suggested that mannitol protects against the development of necrosis by increasing medullary blood flow in combination with a counteractive influence on the cellular swelling, which is known to occur in ischemia.
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PMID:Effect of mannitol, dextran (macrodex), allopurinol, and methylprednisolone on the morphology of the proximal tubule of the rat kidney made ischemic in vivo. 40 53

In 34 anesthetized, open-chest dogs aortic blood pressure was kept at 35-40 mmHg for 3 h to determine if maldistribution of coronary blood flow (CBF) could contribute to the irreversibility of hemorrhagic shock. Six dogs were pretreated with phenoxybenzamine (PBZ) and 11 dogs (3 with PBZ) received hypertonic mannitol infusions in late hemorrhage. Changes of heart rate, cardiac output, and peripheral resistance were similar to those described by others. In untreated dogs total and left ventricular CBF fell, as did coronary vascular resistance. However, minimal coronary resistance after transient ischemia rose progressively and the ratio of subendocardial:subepicardial flow fell, as did the percentage of diastolic coronary flow. Mannitol infusion returned CBF and steady-state and minimal postischemic coronary resistance to control values and also returned to normal the increased myocardial water content found in late hemorrhage. Phenoxybenzamine delayed but did not prevent the rise of coronary vascular resistance or decreased subendocardial flow. These studies suggest that there may be subendocardial ischemia, possibly due to myocardial edema, in hemorrhagic shock.
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PMID:Intramyocardial distribution of blood flow in hemorrhagic shock in anesthetized dogs. 125 9

Impaired metabolism interferes with the active extrusion of intracellular sodium and results in intracellular edema. In the brain and regionally in the kidney, elevation of extracellular osmolality is accompanied by a reduction of ischemic cell swelling and improvement of reflow of blood after arterial occlusion. Studies were therefore performed to examine the effect of elevation of extracellular osmolality on ischemic myocardial physiology and by morphologic examination on the extent of acute injury and subsequent necrosis. Under conditions of controlled hemodynamics, administration of hyperosmotic mannitol resulted in improvement of function of the canine heart with regional ischemia, a lessening of the extent of ischemic injury assessed by electrocardiographic ST segment mapping, and improved total and collateral blood flow. Metabolic studies under conditions of controlled hemodynamics revealed that hyperosmotic mannitol reduced the myocardial oxygen requirement of the ischemic heart. Mannitol dilated large collateral conductance vessels in addition to improving blood flow through the region of myocardial ischemia. Under conditions of ischemia induced by a prolonged reduction in coronary perfusion, hyperosmotic mannitol attenuated the progressive rise in vascular resistance. Direct morphologic examination of areas of myocardium subjected to total interruption of blood flow followed by reflow of blood revealed swelling of both myocardial and capillary endothelial cells early during the reflow period. The extent of swelling was substantially reduced with elevation of the extracellular osmolality with mannitol. Simarilty, osmolality elevation strikingly reduced the extent of eventual myocardial necrosis following prolonged periods of reflow of blood.
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PMID:Effects of hyperosmotic mannitol in reducing ischemic cell swelling and minimizing myocardial necrosis. 125 68

There is as yet no adequate animal mode for human myocardial ischemia. The commonly utilized technique of coronary arterial ligation in large animals may induce regional ischemia but introduces variables that make it difficult to compare studies in different laboratories. A model of global ischemia in an isolated perfused rat heart that offers a rapid, inexpensive means for producing graded, controlled, stable state and reproducible ischemia is described. The technique has been utilized with success to study the hemodynamic and metabolic effects of ischemia and to evaluate pharmacologic interventions designed to protect the ischemic myocardium. Propranolol has been shown to improve bioenergetics and reduce anaerobic glycolysis by a depression of the hemodynamic response of ischemic myocardium. Methylprednisolone appears to exert its primary effect by direct coronary vasodilation, increasing resting or control flow and providing an enhanced reserve when ischemia is imposed. Mannitol improves cardiac performance by reducing the increased myocardial cell water content induced by hypoxia or anoxia.
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PMID:Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size. 125 90

Mannitol has a beneficial effect on ischemic injury following a short-duration forebrain ischemic insult in rats. Using the same animal model, we attempted to show that this effect of mannitol could be traced (via an improvement in cerebral blood flow) to a tempering of the collapse in the high-energy phosphates that occurs during the insult. A 10 min ischemic insult was induced by bilateral carotid artery occlusion followed by a reduction of the blood pressure to 50 mmHg through removal of blood via a tail catheter. 31P NMR spectroscopy was used to monitor the energy state and the pH prior to, during, and after the insult. The studies show that mannitol administered in doses of 0.25 g kg-1 or 1.0 g kg-1 prior to the insult has no significant effect on the high-energy phosphate levels or on the cerebral pH during ischemia, or on their post-ischemia recovery.
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PMID:Mannitol does not affect energy metabolism in forebrain ischemia. 142 Oct 96

In several clinical situations, such as hyposmolar states and hypoxia-ischemia, reductions in the size of the extracellular space are associated with increased seizure susceptibility. Nonsynaptic interactions provide a likely means of mediating the effect of extracellular space on seizure susceptibility. Synchronous bursting of CA1 hippocampal neurons occurs via nonsynaptic mechanisms in solutions containing very low [Ca2+] and excitatory amino acid antagonists. We tested the hypothesis that lowering the osmolality of the extracellular medium could induce nonsynaptic bursting in the dentate gyrus, even though it is normally resistant to this treatment. Extracellular field potentials were recorded in the dentate gyrus and CA1 area of rat hippocampal slices. In the low-[Ca2+] solution with normal osmolality, bursts of population spikes were recorded from the dentate gyrus in only 7% of the slices, but solutions with decreased osmolality induced bursting in 63%. Corresponding values for the CA1 area were 60 and 73%, respectively. Mannitol, which reversed the hyposmolar state, abolished bursting in both regions. This study demonstrates that reducing the size of the extracellular space by lowering extracellular osmolality can transform a seizure-resistant area into one that exhibits robust epileptiform activity.
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PMID:Osmolality and nonsynaptic epileptiform bursts in rat CA1 and dentate gyrus. 154 52

Tandem Scanning Confocal Microscopy (TSCM) allows one to section optically into and record real-time images of living organs and tissues in a noninvasive fashion. In this paper, we will present some initial TSCM observations of subcapsular nephrons in the living, intact kidneys of Munich-Wistar rats and evaluate the nephron's responses to temporary ischemia and to intravenous infusion of mannitol. The rats were anesthetized with Inactin and a laparotomy performed to expose the kidneys. Using a TSCM equipped with a 20 x water-immersion objective, we optically sectioned through the intact kidney capsule and recorded real-time images of living subcapsular glomeruli and uriniferous tubules. The proximal tubule brush border was highly reflective and allowed us to distinguish between the first and second segments of the proximal tubules as well as the distal tubules. Cellular elements of the blood could be seen passing rapidly through peritubular capillaries and individual glomerular capillary loops. With fluorescent filters in place, intravenously injected carboxyfluorescein was seen to pass through the glomerular capillary loops and then progressively through the different segments of the uriniferous tubules. Ligation of the renal artery resulted in rapid swelling of proximal tubule cells into the tubular lumens, loss of reflectiveness of the microvillous brush borders, and closure of the peritubular capillary spaces. Upon release of the ligature, the proximal tubule lumens again became patent, often opening up abruptly and in a zipper-like fashion down the length of the tubules. Increasing the glomerular filtration rate by intravenous infusion of mannitol resulted in increases in tubular luminal and perimeter dimensions. Mannitol also acted as an effective impermeant osmotic agent and prevented most of the cellular swelling which was otherwise seen in response to renal ischemia.
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PMID:Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys. 190 77

Poloxamer 188 has been reported to inhibit thrombosis, decrease whole blood viscosity, and improve perfusion of damaged tissue. Mannitol has free radical scavenging capabilities that might contribute to myocardial salvage after ischemia. Because these agents appear to work in different ways, we studied their cardioprotective properties when they were used separately and in combination. After 75 minutes of left anterior descending coronary artery (LAD) occlusion, dogs received poloxamer 188 (48 mg/kg), mannitol (0.5 gm/kg), or both intravenously during an additional 15 minutes of LAD occlusion and for 45 minutes of reperfusion, whereas control dogs received an equal volume of saline solution. After surgery the animals were maintained for 24 hours and then killed. Areas of myocardial infarction (MI) and risk of infarction (R) were calculated by means of planimetric analysis of slices of myocardium stained with 1.5% triphenyltetrazolium and 0.5% Evans blue dye. The ratio of MI/R (mean +/- standard error of the mean) were: control, 25.6 +/- 1.8% (n = 10); poloxamer 188, 12.7 +/- 2.0% (n = 10); mannitol, 10.6 +/- 2.5% (n = 11); and poloxamer 188 plus mannitol, 8.0 +/- 4.1% (n = 10). Measurement of microvascular blood flow indicated a similar 86% to 91% reduction of blood flow to the area at risk in all treatment groups. Consequently both poloxamer 188 and mannitol appear to increase salvage of ischemic myocardium and a combination of the two may be more effective than either agent alone.
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PMID:Reduction of myocardial infarct size by poloxamer 188 and mannitol in a canine model. 190 29

To study the efficacy of mannitol in reducing cerebral edema and improving the ultimate neuropathologic outcome in perinatal cerebral hypoxia-ischemia, 67 7-day postnatal rats were subjected to unilateral common carotid artery ligation followed by exposure to 8% oxygen at 37 degrees C for 3 hours. Twenty-seven rat pups received a subcutaneous injection of 0.1 ml mannitol in a dosage of 4 mg/kg body wt immediately following cerebral hypoxia-ischemia and every 12 hours thereafter for a total of four doses. Control animals received either no therapy (n = 16) or an equivalent volume of normal saline (n = 24). Mannitol injections in six rat pups not subjected to hypoxia-ischemia produced no mortality but significantly increased serum osmolality from 287 to 361 mos/l (p less than 0.01). Preliminary studies indicated that substantial mortality occurred when greater doses of mannitol were administered to rats. After 48 hours of recovery from hypoxia-ischemia, the animals were killed and their brains were examined for either tissue water content (33 rat pups) or the presence of neuropathologic alterations (34 rat pups). Mannitol significantly reduced (p less than 0.001) brain water content, as a reflection of cerebral edema, in both the ipsilateral (88.5% compared with 90.6% in controls) and the contralateral (85.0% compared with 87.2% in controls) cerebral hemispheres. Mannitol therapy did not ameliorate the incidence, distribution, or severity of tissue injury in the cerebral cortex, subcortical white matter, hippocampus, striatum, or thalamus of the ipsilateral cerebral hemisphere compared with the controls. Thus, while mannitol substantially reduces the extent of cerebral edema following hypoxia-ischemia, no beneficial affect on ultimate brain damage occurs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mannitol therapy in perinatal hypoxic-ischemic brain damage in rats. 211 85


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