niravoline and Intracranial-Hypertension

To ascertain the effects of niravoline (RU 51599, a selective kappa-opioid receptor agonist) on elevated intracranial pressure with mass lesion, the authors experimentally induced intracranial hypertension in cats by progressive inflation of an extradural balloon with physiological saline at the constant rate of 0.5 ml/h for 2.5 h. After 2.5 h, inflation was discontinued, but the balloon remained inflated for an additional 3 h. Immediately after cessation of balloon inflation and while the balloon remained expanded, the control group (n = 8) received ringer's lactate solution only. In the treatment group (n = 8), each cat was treated with an intravenous administration of niravoline at a dose of 1.0 mg/kg immediately after the cessation of balloon inflation and every hour for 3 h in post-inflation period (three injections total). Changes in intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), electroencephalogram (EEG), pupil size, blood gasses and pH, plasma osmolality and electrolytes, and brain water content were studied in both groups. Compared with the untreated group, niravoline treatment produced significant decreases in ICP and significant increases in CPP at 1, 2, and 3 h post-inflation in the presence of an extradural mass lesion. Brain water content was significantly reduced both in the compressed and contralateral hemispheres following niravoline treatment. No significant changes were observed in plasma osmolality and systemic arterial blood pressure following niravoline administration. The results from this present study provide further evidence that niravoline is effective in reducing elevated intracranial pressure, brain water content, and maintaining an adequate cerebral perfusion pressure even in the presence of an extradural mass lesion. Niravoline may offer a new therapeutic modality in head-injury patients with an acute intracranial, expanding mass lesion by providing a safer extended time-period until the mass can be surgically evacuated.

Topics: Analysis of Variance; Animals; Benzeneacetamides; Blood Pressure; Catheterization; Cats; Cerebrovascular Circulation; Electroencephalography; Electrolytes; Female; Functional Laterality; Intracranial Hypertension; Intracranial Pressure; Male; Pupil; Pyrrolidines; Receptors, Opioid, kappa

RU 51599, a selective kappa opioid agonist which is a potent aquaretic, was studied for its effect on acute intracranial hypertension. In ketamine anesthetized cats acute intracranial hypertension was induced by progressive inflation of an epidural balloon with physiological saline at a constant rate of 0.5 ml/hr for three hours. In the control group (n = 8), the balloon was maintained inflated for another an hour after which it was deflated. In the post deflation period monitoring was continued for one hour. In the treatment group (n = 8), cats were treated by an intravenous (i.v.) injection of RU 51599, at a dose of 1 mg/kg every hour at the beginning of balloon inflation, during balloon inflation, at the completion of inflation, and after deflation. Changes in intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), blood gases, serum electrolytes and osmolality, and brain water content water content were studied in both groups. In the control group, epidural brain compression resulted in significant increases in the mean ICP up to 80.7 +/- 9.8 mmHg at 3 hrs (during balloon inflation), 68.6 +/- 8.3 after complete inflation, and 62.1 +/- 11.4 mmHg after deflation (P < 0.01), and significant decreases in CPP to 55.5 +/- 14.0 mmHg at 3 hrs (during balloon inflation), 43.0 +/- 11.2 mmHg after inflation, and 36.3 +/- 9.9 mmHg after deflation (P < 0.01). In the treatment group there were significant decreases in the mean ICP to 35.2 +/- 6.8 mmHg at 3 hrs (during balloon inflation), 32.3 +/- 7.9 after inflation, and 16.1 +/- 3.6 mmHg after deflation (P < 0.01), and significant increases in CPP to 103.2 +/- 6.1 mmHg at 3 hrs (during balloon inflation), 109.0 +/- 8.8 mmHg after inflation, and 102.7 +/- 8.2 mmHg after deflation (P < 0.01). Brain water content was also significantly reduced (P < 0.05). There were no significant changes in the serum electrolytes and osmolality throughout the experiments. Our results suggest that, the mechanism by which RU 51599 reduces ICP is related to reduction in the brain water content.

Topics: Acute Disease; Animals; Benzeneacetamides; Body Water; Cats; Diuretics; Intracranial Hypertension; Pyrrolidines; Receptors, Opioid, kappa