Attenuation of progressive brain hypoperfusion following experimental subarachnoid hemorrhage by large intravenous doses of methylprednisolone.

Abstract

Experimental subarachnoid hemorrhage was produced in chloralose-anesthetized cats by slow injection of 0.5 ml/kg autologous arterial blood into the cisterna magna. As a result, there was an initial (within 5 min) 25.1% decrease in caudate nuclear blood flow as measured by hydrogen clearance. Between 5 min and 3 h postinjection, there was a further and progressive 25.9% decline in caudate blood flow. The hemorrhage also caused a slow increase in intracranial pressure, a decrease in cerebral perfusion pressure, and an increase in caudate vascular resistance. In contrast, the administration of a single 30 mg/kg i.v. dose of methylprednisolone sodium succinate 30 min after the acute hemorrhage resulted in stabilization of caudate blood flow and vascular resistance and some restoration of those parameters toward prehemorrhage values. This effect was not correlated with a decrease in intracranial pressure or an increase in cerebral perfusion pressure. A 15 mg/kg i.v. dose of the drug had only a slight effect on caudate blood flow. A 60 mg/kg i.v. dose, while initially supportive, lost its effect during the later stages of the experiment, indicating a sharp biphasic dose-response relationship for the effect of methylprednisolone on caudate blood flow after subarachnoid hemorrhage. However, of the three doses, only 60 mg/kg significantly decreased the slow posthemorrhage rise in intracranial pressure. The beneficial effect of the 30 mg/kg i.v. dose of the drug on caudate blood flow, separate from an effect on the slow rise in intracranial pressure, suggests that the steroid support of caudate perfusion is due to a direct protective effect of the drug on the microvasculature. Based on previous studies showing an identical dose-response pattern for the ability of methylprednisolone to prevent posttraumatic lipid peroxidation of central nervous system tissue and progressive ischemia development, the possibility of the drug's inhibition of hemorrhage-initiated vasoconstrictor prostanoid action and microvascular lipid peroxidation is proposed.

• Authors: E D Hall, M A Travis
• Journal: Experimental neurology (Exp Neurol) Vol. 99 Issue 3 Pg. 594-606 (Mar 1988) ISSN: 0014-4886 [Print] United States
• PMID: 3342842 (Publication Type: Journal Article)

Chemical References

• Methylprednisolone

Topics

• Animals
• Cats
• Cerebrovascular Circulation (drug effects)
• Female
• Injections, Intravenous
• Intracranial Pressure (drug effects)
• Methylprednisolone (administration & dosage, therapeutic use)
• Subarachnoid Hemorrhage (drug therapy, physiopathology)