Document Detail


In vitro therapy with dobutamine, isoprenaline and sodium nitroprusside protects vascular smooth muscle metabolism from subarachnoid haemorrhage induced cerebral vasospasm.
MedLine Citation:
PMID:  11534694     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients with cerebral vasospasm stimulates vasoconstriction and oxygen consumption in the porcine carotid artery in vitro. Stimulation of oxygen consumption has been used as an in vitro model of vasospasm to assess the relative benefits of nimodipine, isoprenaline, dobutamine, and sodium nitroprusside (SNP). METHOD: Samples of human CSF were obtained from SAH patients and applied to de-endothelialised porcine carotid artery. Stimulation of oxygen consumption (as an in vitro marker for a stimulation of the vessels) was monitored and the effects of SNP, isoprenaline, dobutamine or nimodipine were measured. FINDINGS: The CSF from SAH patients with evidence of vasospasm stimulated oxygen consumption to 0.91 +/- 0.17 (microM O2/min/g dry wt, +/- SD p < or = 0.01) and CSF from SAH patients without vasospasm did not significantly stimulate oxygen consumption 0.27 +/- 0.02, with 0.23 +/- 0.03 (microM O2/min/g dry wt) being an unstimulated rate of respiration for the porcine carotid artery. SNP, isoprenaline or dobutamine significantly (p < or = 0.01) decreased the stimulation of oxygen consumption of the porcine carotid artery whereas nimodipine did not. In a cohort of 41 SAH patients who received nimodipine alone or nimodipine and dobutamine, the in hospital mortality rate of the patients who received only nimodipine was 42% as compared to an in hospital mortality rate of 17% in the nimodipine plus dobutamine group P < or = 0.076). INTERPRETATION: The in vivo data on the 41 patients is not statistically significant, so further studies are required to determine if the differences are important. SNP, isoprenaline and dobutamine significantly decreased oxygen consumption of the porcine carotid arteries exposed to CSF from SAH patients who had vasospasm whereas nimodipine did not. Our in vitro results suggest that these compounds require further study in patients with SAH who are at risk for vasospasm because they may have a direct benefit for the vasospastic arteries.
Authors:
J F Clark; G J Pyne; J Choutka; J A Carrozzella; J Khoury; J P Broderick; T A Cadoux-Hudson
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Acta neurochirurgica     Volume:  143     ISSN:  0001-6268     ISO Abbreviation:  Acta Neurochir (Wien)     Publication Date:  2001  
Date Detail:
Created Date:  2001-09-05     Completed Date:  2001-12-26     Revised Date:  2009-11-11    
Medline Journal Info:
Nlm Unique ID:  0151000     Medline TA:  Acta Neurochir (Wien)     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  721-8     Citation Subset:  IM    
Affiliation:
Department of Neurology, University of Cincinnati, OH, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Agonists / pharmacology*
Animals
Carotid Arteries
Disease Models, Animal
Dobutamine / pharmacology*
Humans
Isoproterenol / pharmacology*
Muscle, Smooth, Vascular / drug effects*,  metabolism
Nitroprusside / pharmacology*
Oxygen Consumption / drug effects*
Subarachnoid Hemorrhage / cerebrospinal fluid,  complications*,  metabolism
Swine
Vasodilator Agents / pharmacology*
Vasospasm, Intracranial / etiology,  metabolism,  prevention & control*
Grant Support
ID/Acronym/Agency:
1RO1NS36695/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Vasodilator Agents; 15078-28-1/Nitroprusside; 34368-04-2/Dobutamine; 7683-59-2/Isoproterenol

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