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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the concentrations of carnitine, long-chain acylcoenzyme A, and long-chain acylcarnitine in ischemic myocardium parallel those in ischemic brain. Since carnitine treatment reverses these changes and improves function in ischemic hearts, we examined whether carnitine given to rats before focal cerebral ischemia (produced by tandem right common carotid artery and middle cerebral artery occlusion) alters infarct volume in four separate experiments. Mannitol was used to control for the osmotic effect of carnitine on brain edema in one experiment. While carnitine was found to significantly decrease infarct volume compared with saline in one experiment (p less than 0.05, Student's t test), this result could not be replicated in the subsequent three experiments. Because the positive treatment effect was not reproducible despite similar experimental conditions, the result of the first experiment was attributed to a type I error. Mannitol also showed no significant effect on infarct volume. This study emphasizes the need for concurrent controls with each group of treated animals and the need for replicating the results of a single experiment when testing for drug efficacy in animal models of focal cerebral ischemia.
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PMID:Carnitine treatment for stroke in rats. 233 61

The effects of hypertonic mannitol on postischemic cerebral circulation were studied in 20 dogs. Mannitol, 2 g/kg iv, was infused into ten dogs during a 2-h period starting 1.5 h after 6 min of complete cerebral ischemia. One hour postischemia, regional cerebral blood flow (rCBF) was 36% in the control group (ten dogs) and 39% in the mannitol group. In the control group, rCBF increased gradually thereafter to 70% of the preischemic value 10 h postischemia, whereas the restoration of rCBF was suppressed in the mannitol group. During the postischemic period, intracranial pressure (ICP) increased significantly in the control group, but it did not change significantly in the mannitol group. The effects of mannitol on rCBF and ICP in the present study can be explained primarily by decreased body water due to urinary loss. The administration of mannitol does not necessarily improve postischemic cerebral circulation.
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PMID:Effects of mannitol on cerebral circulation after transient complete cerebral ischemia in dogs. 308

Fluosol-DA (Perfluorochemical Blood Substitutes) are small particle fluorocarbons suspended in an emulsion and have a high propensity for carrying oxygen and carbon dioxide. Fluosol-DA was investigated for the modification of acute focal cerebral ischemia and compared with mannitol. A total of 36 adult cats was divided into three groups and underwent transorbital microtourniquet ligation of the middle cerebral artery (MCA). Control animals were given intravenous isotonic saline. Animals in the experimental groups were treated with either intravenous Fluosol-DA or Mannitol. All animals were nursed in an oxygen chamber and four cats from each group were sacrificed at 1, 3 and 6 hours after MCA occlusion. The results of macroscopic and histological examination of the brain suggested Fluosol-DA had a remarkable protective effect on acute focal cerebral ischemia which was in keeping with the observed neurological outcome. It is suggested that Fluosol-DA may support flow in the microcirculation and the small particles of Fluosol-DA may be able to reach the area of ischemia via collaterals by decreasing blood viscosity, preventing narrowing of the arteriolar and capillary lumen and increasing the cerebral blood flow.
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PMID:[Protective effect of fluosol-DA in acute cerebral ischemia (author's transl)]. 680 9

Mannitol, the osmotic diuretic used in neuroanaesthesia and neurointensive care, has, in addition to its osmotic properties, various effects upon haemodynamics, cerebral blood flow and cerebral blood volume. Three factors are proposed to contribute to mannitol's capacity to lower intracranial pressure and to improve cerebral compliance: cerebral dehydration, and two forms of autoregulation-mediated vasoconstriction. In the case of viscosity autoregulation, it is admitted that changes in blood viscosity after mannitol result in reflex vasoconstriction to maintain cerebral blood flow constant. It has also been proposed that when mannitol administration results in increased cerebral perfusion pressure, vasoconstriction may occur in vascular beds in which autoregulation to perfusion pressure is preserved. On the basis of its effects on cerebral blood flow and free radical scavenging properties, mannitol has recently been investigated as a cerebral protective agent, with the capacity to reduce or prevent damage due to cerebral ischaemia. Finally, mannitol may be injected into a carotid or a vertebral artery to produce blood-brain barrier breakdown, thus improving the brain penetration of chemotherapeutic agents.
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PMID:[Use of mannitol in neuroanesthesia and neurointensive care]. 767 91

We have evaluated the effect of mannitol on focal cerebral ischemia using T2-weighted magnetic resonance (MR) imaging and intravoxel incoherent motion (IVIM) MR imaging. The left middle cerebral artery (MCA) was exposed via the transorbital approach in 20 adult cats and occluded just proximal to the origin of the perforating arteries. Seven cats in treatment group received mannitol (0.5 g/kg i.v.) at 0, 6, 12 and 18 hours after MCA occlusion. The other 13 cats received saline and served as controls. Sequential MR coronal images were obtained at 2, 4, 6, and 24 hours after MCA occlusion using a GE Signa (1.5 tesla) system. IVIM MR imaging demonstrated ischemic cerebral injury as a sharply demarcated area at 2 hours after MCA occlusion in control group, while T2-weighted MR imaging failed to show clear evidence of the injury until 2-6 hours. At 24 hours after MCA occlusion, the infarcted area in the mannitol treatment group was 36.9 +/- 7.7% (S.E.M) of the left hemisphere, as compared to 57.3 +/- 5.3% in control group (p < 0.05). Mannitol has beneficial effect on ischemic injury.
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PMID:Effect of mannitol on focal cerebral ischemia evaluated by magnetic resonance imaging. 797 53

Acute liver failure is a multiorgan syndrome with dramatic clinical features and, often, a fatal outcome. It is characterized by the onset of coma and coagulopathy within 6 months, and usually in < 6 weeks, from onset of illness. Viral hepatitis, drug-related liver injury, and the alcohol-acetaminophen syndrome are the most common etiologies. Altered mental status accompanied by jaundice is a hallmark of acute liver failure. A unique feature is the evolution of increased intracranial pressure due to cerebral edema. The resulting cerebral ischemia and brainstem herniation account for approximately 50% of deaths in patients with acute liver failure. Mannitol therapy may successfully treat most patients with high intracerebral pressure. Most patients demonstrate features of the multiple organ failure syndrome, including a shock-like state, renal failure, and occasionally respiratory distress syndrome. Close monitoring of volume status is necessary, since administration of large quantities of fluid may be required. Infection is also common; most pathogens are gram-positive, and fungal infections are also seen. Because an optimum therapy for acute liver failure does not yet exist, liver transplantation should be considered early, before advanced levels of coma develop. Alternative, experimental treatment modalities include heterotopic liver grafting, administration of hepatocyte growth factor, use of an extracorporeal liver-assist device, and liver cell transplantation, but none of these has attained widespread use.
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PMID:Acute liver failure. 810 86

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

The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or energy deprivation was measured by high-performance liquid chromatography. Exposing the slices to hyposmotic stress by lowering extracellular NaCl caused a 10-fold release of taurine (p < 0.01) and over a twofold increase of gamma-aminobutyric acid (GABA) and glutamate (p < 0.01). These changes were reversed by mannitol. Exposure to combined glucose and oxygen deprivation (energy deprivation) caused a 50-fold increase in the release of GABA, a 40-fold increase in glutamate release (p < 0.01), and a twofold to sixfold increase in taurine, aspartate, glycine, asparagine, serine, and alanine release (p < 0.05) but no change in glutamine. Energy deprivation increased the water content by 21%. Mannitol blocked this increase and further enhanced the release of glutamate and aspartate (p < 0.01) but not of GABA. The permissivity of the amino acids was plotted against the pI (pH at isoelectric point) and hydropathy indexes. Energy deprivation increased the permissivity in the following order: acidic > neutral > basic. Among neutral amino acids, permissivity increased with increasing hydrophobicity. These results indicate that the mechanisms of amino acid release are different during cerebral ischemia and hyposmotic stress.
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PMID:Release of brain amino acids during hyposmolar stress and energy deprivation. 882 65

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 pressure depends on cerebral tissue volume, cerebrospinal fluid volume (CSFV) and cerebral blood volume (CBV). Physiologically, their sum is constant (Monro-Kelly equation) and ICP remains stable. When the blood brain barrier (BBB) is intact, the volume of cerebral tissue depends on the osmotic pressure gradient. When it is injured, water movements across the BBB depend on the hydrostatic pressure gradient. CBV depends essentially on cerebral blood flow (CBF), which is strongly regulated by cerebral vascular resistances. In experimental studies, a decrease in oncotic pressure does not increase cerebral oedema and intracranial hypertension (ICHT). On the other hand, plasma hypoosmolarity increases cerebral water content and therefore ICP, if the BBB is intact. If it is injured, neither hypoosmolarity nor hypooncotic pressure modify cerebral oedema. Therefore, all hypotonic solutes may aggravate cerebral oedema and are contra-indicated in case of ICHT. On the other hand, hypooncotic solutes do not modify ICP. The osmotic therapy is one of the most important therapeutic tools for acute ICHT. Mannitol remains the treatment of choice. It acts very quickly. An i.v. perfusion of 0.25 g.kg-1 is administered over 20 minutes when ICP increases. Hypertonic saline solutes act in the same way, however they are not more efficient than mannitol. CO2 is the strongest modulating factor of CBF. Hypocapnia, by inducing cerebral vasoconstriction, decreases CBF and CBV. Hyperventilation is an efficient and rapid means for decreasing ICP. However, it cannot be used systematically without an adapted monitoring, as hypocapnia may aggravate cerebral ischaemia. Hyperthermia is an aggravating factor for ICHT, whereas moderate hypothermia seems to be beneficial both for ICP and cerebral metabolism. Hyperglycaemia has no direct effect on cerebral volume, but it may aggravate ICHT by inducing cerebral lactic acidosis and cytotoxic oedemia. Therefore, infusion of glucose solutes is contra-indicated in the first 24 hours following head trauma and blood glucose concentration must be closely monitored and controlled during ICHT episodes.
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PMID:[The internal environment and intracranial hypertension]. 975 May 95


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