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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema states, to increase urine flow and flush out debris from the renal tubules in patients with acute tubular necrosis, and to increase toxin excretion in patients with barbiturate, salicylate or bromide intoxication. As an obligate extracellular solute it may be useful to ameliorate symptoms of the dialysis disequilibrium syndrome, to decrease cerebral edema following trauma or cerebrovascular accident, and to prevent cell swelling related to renal ischemia following cross-clamping of the aorta. Largely unexplored uses for mannitol include its use as an osmotic agent in place of dextrose in peritoneal dialysis solutions, its use to maintain urine output in patients newly begun on hemodialysis, and its use to limit infarct size following acute myocardial infarction.
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PMID:Mannitol. 38 67

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)
Stroke 1990 Aug
PMID:Mannitol therapy in perinatal hypoxic-ischemic brain damage in rats. 211 85

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.
Stroke 1990 May
PMID:Carnitine treatment for stroke in rats. 233 61

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.
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PMID:Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure. 250 26

The use of mannitol in the management of head injury has been considered a threat to hemodynamic stability in hypotensive multiply injured patients. To evaluate this contention, we compared mannitol with normal saline administration in a canine model combining elevated intracranial pressure (ICP) and hemorrhagic shock. Mongrel dogs were bled to and maintained at a mean arterial pressure (MAP) of 60 mm Hg for 30 minutes. Following this, ICP was elevated to and sustained at 25 mm Hg for 45 minutes by inflating an epidural balloon. The dogs were then randomized to resuscitation with 2 g/kg of mannitol in saline (total volume, 20 mL/kg; n = 5) or 20 mL/kg of normal saline alone (n = 5). All dogs were successfully resuscitated, and MAP returned to baseline levels in both groups. ICP was significantly lower and urine output significantly higher in the mannitol group than in saline controls (P less than .01). Moreover, cerebral perfusion pressure, cardiac index, and left ventricular stroke work index were significantly improved in dogs given mannitol versus controls during the first hour of resuscitation (P less than .05). Mannitol ameliorates increases in ICP without compromising hemodynamic resuscitation in a canine model of concomitant increased ICP and shock.
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PMID:Hemodynamic effect of mannitol in a canine model of concomitant increased intracranial pressure and hemorrhagic shock. 313 65

Using the canine thalamic infarction model, we have investigated the effects of 10 ml/kg of 20% mannitol on the hemodynamics of the ischemic brain. Mannitol was found to cause an increase in rCBF, but it is not marked in animals with severe ischemic foci. Increases were statistically significant in the animals with moderate ischemia. Increases in rCBF due to mannitol administration lasted for about 1 hour, as did the rise in serum osmolarity. The actual relationship between these two parameters, remains unclear.
Stroke
PMID:Effect of mannitol on rCBF in canine thalamic ischemia--an experimental study. 640 77

In a previous paper, the authors showed that mannitol causes cerebral vasoconstriction in response to blood viscosity decreases in cats. The present paper describes the changes in intracranial pressure (ICP) and cerebral blood flow (CBF) after mannitol administration in a group of severely head-injured patients with intact or defective autoregulation. The xenon-133 inhalation method was used to measure CBF. Autoregulation was tested by slowly increasing or decreasing the blood pressure by 30% and measuring CBF again. Mannitol was administered intravenously in a dose of 0.66 gm/kg; 25 minutes later, CBF and ICP were measured once again. In the group with intact autoregulation, mannitol had decreased ICP by 27.2%, but CBF remained unchanged. In the group with defective autoregulation, ICP had decreased by only 4.7%, but CBF increased 17.9%. One of the possible explanations for these findings is based on strong indications that autoregulation is mediated through alterations in the level of adenosine in response to oxygen availability changes in cerebral tissue. The decrease in blood viscosity after mannitol administration leads to an improved oxygen transport to the brain. When autoregulation is intact, more oxygen leads to decreased adenosine levels, resulting in vasoconstriction. The decrease in resistance to flow from the decreased blood viscosity is balanced by increased resistance from vasoconstriction, so that CBF remains the same. This might be called blood viscosity autoregulation of CBF, analogous to pressure autoregulation. Vasoconstriction also reduces cerebral blood volume, which enhances the effect of mannitol on ICP through dehydration of the brain. When autoregulation is not intact there is no vasoconstriction in response to increased oxygen availability; thus, CBF increases with decreased viscosity. With the lack of vasoconstriction, the effect on ICP through dehydration is not enhanced, so that the resulting decrease in ICP is much smaller. Such a mechanism explains why osmotic agents do not change CBF but decrease ICP in normal animals or patients with intact vasoconstriction, but do (temporarily) increase CBF in the absence of major ICP changes after stroke.
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PMID:Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely head-injured patients. 643 72

Experiments were conducted to evaluate the pulmonary vascular responses of lightly anesthetized clinically healthy male broilers during acute metabolic acidosis induced by bolus i.v. injections or constant i.v. infusions of HCl. In Experiment 1, broilers received consecutive 1.5 mL i.v. bolus injections of 2.5% mannitol (volume control) and 0.4 N, 0.8 N, and 1.2 N HCl in 2.5% mannitol. Following each injection, equivalent concentrations of mannitol or HCl were infused i.v. at a rate of 0.05 mL/min.kg BW. In Experiment 2, repeated bolus injections of 2.5% mannitol and 1.2 N HCl were administered during ongoing constant infusion of 2.5% mannitol. The following variables were evaluated: pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, total peripheral resistance, cardiac output, stroke volume, heart rate, respiratory rate, hematocrit (HCT), and arterial blood gas (PaO2, PaCO2, pH, HCO3-). Mannitol alone did not alter any of the variables. The HCl loading protocols acidified the arterial blood to sustained (constant infusion) or transient (bolus injection) values averaging between pH 7.2 and 7.3. In both experiments, bolus injections of 1.2 N HCl caused transient increases in pulmonary vascular resistance and pulmonary arterial pressure, coincident with decreases in mean arterial pressure and cardiac output. When HCl was infused at a constant rate in Experiment 1, the arterial blood hydrogen ion concentration, [H+], was positively correlated with pulmonary arterial pressure and cardiac output, negatively correlated with mean arterial pressure and total peripheral resistance, and was not correlated with pulmonary vascular resistance. During constant i.v. infusion of mannitol or HCl in both experiments, pulmonary arterial pressure was positively correlated with pulmonary vascular resistance and cardiac output. Overall, bolus injections of 1.2 N HCl consistently triggered transient pulmonary vasoconstriction (increased pulmonary vascular resistance), leading to a transient increase in pulmonary arterial pressure in spite of opposing changes in cardiac output and mean arterial pressure. In contrast, equivalent or greater increases in [H+] during constant i.v. infusion of HCl caused a substantially lower increment in pulmonary arterial pressure, which, in, turn was primarily attributable to increases in cardiac output rather than pulmonary vascular resistance. Increments in either pulmonary vascular resistance or cardiac output induced by metabolic acidosis would be expected to contribute to the onset of pulmonary hypertension syndrome (PHS, ascites) in broilers.
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PMID:The infusion rate dependent influence of acute metabolic acidosis on pulmonary vascular resistance in broilers. 949 99

Bolus i.v. injections of 1.2 N HCl elicit a rapid but transient pulmonary vasoconstriction in broiler chickens. In mammals, the pulmonary vasoconstrictive response to bolus acid injection depends on increased synthesis of thromboxane A2; however, the vascular responsiveness of domestic fowl to thromboxane previously had not been evaluated. In the present study, we tested the hypothesis that, if HCl triggers pulmonary vasoconstriction by stimulating thromboxane A2 synthesis in broilers, then bolus i.v. injections of the potent thromboxane A2 mimetic U44069 (9,11-dideoxy-9alpha,11alpha-epoxy-methanoprostaglandin++ + F2alpha; 1 micromol/mL; 0.5 mL injected volume) should trigger hemodynamic responses similar to those elicited by HCl (1.2 N; 1.5 mL injected volume). Both HCl and the thromboxane mimetic elicited twofold or greater increases in pulmonary vascular resistance, which in turn increased pulmonary arterial pressure by 50% despite concurrent reductions in cardiac output. The reductions in cardiac output were associated with reductions in stroke volume but not heart rate. The thromboxane mimetic also increased the total peripheral resistance, which minimized the reduction in mean systemic arterial pressure associated with the decrease in cardiac output. In contrast, HCl injections did not increase total peripheral resistance; consequently, the reduction in cardiac output caused the mean systemic arterial pressure to decrease by 30 mm Hg. Mannitol (2.5%; 1.5 mL) was injected i.v. as a volume control, and had no influence on any of the variables. This study provides the first direct evidence that thromboxane is a potent pulmonary vasoconstrictor in broilers, and provides support for the hypothesis that thromboxane mediates the pulmonary vasoconstrictive response to bolus i.v. injections of HCl. The differential response of the systemic vasculature to the thromboxane mimetic and HCl may indicate that cardiopulmonary responses to HCl injections are not mediated solely via thromboxane production. Alternatively, a direct dilatory effect of elevated hydrogen ion concentrations on the systemic vasculature may have counteracted any tendency for simultaneously evolved endogenous thromboxane to elicit systemic vasoconstriction.
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PMID:Thromboxane mimics the pulmonary but not systemic vascular responses to bolus HCl injections in broiler chickens. 1022 68

Brain oedema is a major factor contributing to the poor outcome of subjects with acute ischaemic stroke but the use of mannitol and other hyperosmolar agents in this setting is controversial and hardly debated. Recent data have demonstrated that mannitol at concentrations which may be achieved in clinical conditions and hyperosmotic stress itself can activate the process of apoptotic cell death. This could have important clinical implications as apoptosis is involved in the more gradual loss of neurons in the penumbra zone surrounding the core of ischaemic stroke where neurons die immediately from oxygen starvation. Mannitol has the potential to activate inflammatory mediators, induce oxidant stress and produce rebound cell swelling and, through these mechanisms, can further aggravate the neuronal injury due to ischaemia. Furthermore, apoptosis in ischaemic areas closely parallels the timing of brain oedema and this suggests that a cause-effect relationship links the two phenomena rather than simply a temporal correlation. On this basis, it is crucial that emergency-physicians critically rethink the management strategy of brain oedema associated with ischaemic stroke.
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PMID:The puzzle of neuronal death and life: is mannitol the right drug for the treatment of brain oedema associated with ischaemic stroke? 1064 27


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