Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction.

103

Background and Purpose-Cerebral edema develops very early after the onset of focal cerebral ischemia and may be a major factor in early disability after an acute ischemic stroke. There have been very limited studies on the usefulness of antiedemic agents as neuroprotective agents in the setting of focal cerebral ischemia. We tested the neuroprotective effects of a new potent nonpeptide vasopressin receptor V 1 antagonist, SR-49059, in a focal embolic stroke model in rats. Methods-Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA).Infarction volume was measured at 48 hours after the MCA occlusion. Neurological deficits, ischemic brain edema, seizure activity, and mortality and hemorrhage rates were also documented. Results-Treatment with SR-49059 (2 mg/kg), initiated immediately after MCA occlusion, significantly reduced infarction volume (PϽ0.05) measured at 48 hours after the arterial occlusion. In animals in which the treatment was delayed for 1 hour after MCA occlusion, infarction volume was also reduced significantly (PϽ0.05). Infarction volume in the rats that received the drug at 3 or 6 hours after MCA occlusion was not different from that in the vehicle-treated group. Treatment with SR-49059, when started early after the arterial occlusion, also reduced neurological deficits and ischemic brain edema. Injection of drug at a higher dose (30 mg/kg) also reduced infarction volume and improved functional recovery but was not superior to the lower dose (2 mg/kg) when the drug was administrated at 1 hour after MCA occlusion. Conclusions-Our data show that the selective vasopressin receptor antagonist SR-49059 is a potent neuroprotective agent when used early after onset of arterial occlusion in an embolic focal ischemia model in rats. Further studies are needed in stroke models to better understand its neuroprotective properties when used alone or in combination with thrombolysis. (Stroke. 2002;33:3033-3037.)

Section: Discussionmentioning

confidence: 99%

Effects of Nonpeptide V ₁ Vasopressin Receptor Antagonist SR-49059 on Infarction Volume and Recovery of Function in a Focal Embolic Stroke Model

Shuaib

Wang

Yang

et al. 2002

103

“…28 Following temporary ischemia induced in baboons by occluding the carotid and vertebral arteries bilaterally, glycerol injection (1 g/kg) was found to be effective in reducing intracranial pressure and increasing cerebral blood flow. 29 In patients with cerebral infarction, numerous studies have evidenced the effectiveness of glycerol in reducing cerebral edema [30][31][32][33][34][35][36][37][38] and increasing cerebral blood flow. [36][37][38] Other studies 39 " 42 failed to observe any benefit from the use of glycerol, especially in patients with severe disability.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with recent cerebral infarction, glycerol infusion led to a decrease in cerebral oxygen consumption and carbon dioxide production whereas glucose consumption, pyruvate and lactate production by brain were found to be unchanged. 36 - 38 It was hypothesized that glycerol may cause a reversal of uncoupled oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of hypertonic glycerol and urea on brain edema, energy metabolism and blood flow following cerebral microembolism in the rat. Deleterious effect of glycerol treatment.

Bralet¹,

Beley²,

Bralet³

et al. 1983

SUMMARY Cerebral microembolism was performed in rats by injecting radioactive calibrated 50 /x microspheres into the left internal carotid artery. The use of radioactive microspheres as embolic agents enabled the number of microspheres to be determined in each cerebral hemisphere. Edema was assessed 24 h after embolization by measuring brain water, sodium, and potassium content. Equiosmolal doses (40 mmol/kg) of glycerol or urea were injected i.p. at various times before sacrifice. Both treatments caused similar changes in water and electrolyte content, brain dehydration being maximal 30 min after urea and 2 h after glycerol injection. Cerebral energy metabolism and regional blood flow were evaluated at the times of maximal brain dehydration. Urea treatment resulted in an improvement of the cerebral circulation whereas glycerol treatment led to a deterioration of cerebral blood flow which cannot be explained by failure to reduce edema and the consequent microcirculatory impairment. Urea treatment had no marked effect on cerebral energy metabolism whereas glycerol injection resulted in an important increase in brain lactate level which may be relevant to the impairment of cerebral reperfusion. These results point out that administration of a metabolized solute like glycerol may exert deleterious effects on the ischemic brain.Stroke Vol 14, No 4, 1983 BRAIN EDEMA, a serious complication of cerebral infarction, is known to increase intracranial pressure and to alter cerebral hemodynamics and metabolism. Hyperosmolar solutions have been used extensively to reduce cerebral edema.' The mechanism of action of the hypertonic agents which do not readily cross the blood-brain barrier (BBB) is assumed to be related to intravascular hypertonicity leading to the extraction of tissue water by the osmotic gradient they create across the BBB. Among the hyperosmolar agents, glycerol attracted more attention than the other substances because in addition to its osmotic activity it can be metabolized by brain.2 " 4 Numerous experimental works [5][6][7][8][9][10][11][12][13] have reported the effect of glycerol or urea on brain water and electrolytes or on intracranial pressure but little is known about their actions on cerebral circulation and metabolism of the ischemic brain. The aim of the present study was to assess the effect of glycerol on brain edema, cerebral blood flow and metabolism compared to an equivalent dose of the metabolically inert urea. The study was performed on an experimental model of cerebral microembolism in the rat. I4 The cerebral injury in this model reproducibly results in important brain edema within 24 h of embolization. Brain water and electrolytes were determined at various times after injection of glycerol or urea. Regional cerebral blood flow and brain energy metabolism were evaluted at the times of maximal brain dehydration.Methods The experiments were performed on male SpragueDawley rats (Iffa Credo) weighing 280-320 g. Production and Evaluation of EmbolizationCerebral microembolism was produc...

“…In human stroke, increase of blood flow to ischemic territories and improvement in ischemic brain energy metabolism after glycerol administration have also been postulated. 35 The occurrence of a rebound phenomenon has been controversial, 12 but glycerol has the theoretical advantage over other osmotics in being metabolized by the brain on crossing BBB, thus reducing the risk of rebound edema. Using MRI before and after glycerol administration in 6 patients with large hemispheric infarction, no effect on tissue shift and noninfarcted hemisphere volume has been observed.…”

Section: Glycerolmentioning

confidence: 99%

Antiedema Therapy in Ischemic Stroke

Bardutzky

Schwab

2007

174

103

Abstract-Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbiturate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive. (Stroke. 2007;38:3084-3094.)