A novel treatment for ischemic intracranial hypertension in cats.

Abstract

There is no accepted efficacious treatment for ischemic cerebral edema. We show in a cat model of focal cerebral ischemia that infarct volume can be reduced ( A lthough there is active investigation into many aspects of the treatment of acute stroke, there is currently no accepted treatment for a patient so afflicted. Death during the acute phase occurs due to intractable brain swelling and herniation.1 Brain swelling and intracranial pressure (ICP) elevation become maximal in 2-4 days. The brain swelling and edema associated with transtentorial herniation are responsible for the death of approximately 10% of patients with ischemic stroke. 2For these patients there is no uniformly acceptable treatment that reduces or blocks the development of cerebral edema and the subsequent rise in ICP. Surgical decompression and medical treatment with hyperosmolar agents have had limited success in the treatment of ischemic cerebral edema, 3 ' 4 and corticosteroids have not been shown to be of benefit in ischemic vascular disease. 5 We have shown in a cat model of focal cerebral ischemia that we can reduce the volume of infarction by ventriculocisternal perfusion with various oxygenated fluorochemical nutrient emulsions.6 -10 A separate, but perhaps related, effect of such ventriculocisternal perfusion is the reduction of ICP. Materials and MethodsWe used 21 male closed-colony cats (Liberty Laboratories, Reading, Pa.) weighing 3-5 kg. The animals were fasted overnight and each was premedicated with 0.05 mg/kg i.m. atropine. Anesthesia was induced with 50 mg methohexital sodium, and maintained with 50 mg a-chloralose-urethane every 8 hours supplemented with 70% N 2 O in 30% O 2 . All surgical sites were infiltrated with 0.5% lidocaine before incision.Focal cerebral ischemia was produced by application of an aneurysm clip on the middle cerebral artery as close as possible to its origin off the internal carotid artery through a retro-orbital exposure. The orbit was then filled with absorbable gelatin sterile powder, and the eyelid was sutured shut. In all cats, an inflow catheter was placed in the left lateral ventricle using a stereotaxic instrument (David Kopf Instruments, Tujunga, Calif.) and in 15 cats an outflow catheter was placed in the cisterna magna under microscopic visualization. The cat remained in the stereotactic frame for the remainder of the experiment. The other six cats were not perfused, did not have outflow catheters placed, and served as controls. Of the 15 cats with catheters, eight were perfused with an oxygenated nutrient solution not containing fluorochemical and seven were perfused with oxygenated fluorochemical emulsion.Arterial blood samples were obtained every 2 hours or as necessary for monitoring and maintaining the following physiologic parameters throughout the experiment: Pao 2 at >100 torr, Paa>2 at 25-35 torr, pH at 7.35-7.45, total CO 2 concentration at 17-24 by guest on May 11, 2018 http://stroke.ahajournals.org/ Downloaded from

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

“…The early EYP-based concentrated PFC emulsions have demonstrated O 2 delivery efficacy as well. Intracoronary infusion of Therox in dogs was more effective in maintaining ventricular function than a non-O 2 -carrying perfusion solution; intracranial hypertension and infarct volume following experimental stroke in cats were significantly reduced by perfusion of the brain (through the ventriculocisternal route) with an F-44E/EYP emulsion; substantially enhanced cardioplegic protection was obtained in an isolated rat heart model of cardioplegic arrest with Addox -type emulsions. , …”

“…Therox , a concentrated emulsion of F-44E 5.12a (48% v/v or 83% w/v) with a particle size of 0.25 μm, was developed by DuPont for research purposes. Therox and other F-44E emulsions were used in various studies. − Another F-44E emulsion is being investigated by Neuron Therapeutics Inc. for treatment of stroke. Adamantech locked onto a mixture of cyclic PFCs obtained by CoF 3 fluorination of methyladamantane (again in the belief that cyclization would help excretion) to produced Addox , a 40% w/v PFC emulsion. ,, Both Therox and Addox were EYP-based and had a shelf life of 1 year at 4 °C.…”

“…Intriguingly, it was shown that isolated brain slices could recover functionality when reoxygenated after up to 4 h in a nitrogen environment, leading to the hypothesis that microvascular dysfunction is the primary cause of brain damage and that neuronal changes and death are only secondary to these vascular effects . An original treatment of stroke was subsequently experimented that consisted of infusing an oxygenated, nutrient-enriched PFC emulsion directly into the cerebral ventricle (the cavity that contains the cerebrospinal fluid that bathes the brain), thus bypassing the clogged blood vessels. , Cats with experimental cerebral ischemia, when perfused in this fashion (ventriculocisternal perfusion) with an oxygenated F-44E emulsion within 3 h after onset of ischemia, demonstrated dramatically reduced infarct size and improved electrical brain activity . Other studies involving administration of a PFC into the cerebral ventricle were aimed at radiographic imaging of the central nervous system, at preventing brain tissue hypoxia, and at preventing paraplegia after aortic occlusion …”

“…Therox and other F-44E emulsions were used in various studies. [1610][1611][1612][1613] Another F-44E emulsion is being investigated by Neuron Therapeutics Inc. for treatment of stroke. Adamantech locked onto a mixture of cyclic PFCs obtained by CoF 3 fluorination of methyladamantane (again in the belief that cyclization would help excretion) to produced Addox, a 40% w/v PFC emulsion.…”

Ischemic Attack as Seen by a Neuroresuscitator: Current Approaches to Intensive Care

“…Предложена техника вентрикулосто мии боковых желудочков мозга с последующей их перфузией ревоксином. Применение данного мето да позволяет сокращать размеры инфаркта мозга и снижать ВЧД [24,25,26].…”