title: Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo.
abstract: OBJECTIVE
  Intrathecal bolus administration of nitric oxide donors and calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Intrathecal continuous administration of these substances for CVS prevention has not been extensively evaluated. This study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing delayed CVS associated with SAH in an animal model in vivo.
  
  
  METHODS
  New Zealand White rabbits were randomly assigned to six groups: no SAH/NaCl, no SAH/NO, no SAH/nimodipine, SAH/NaCl, SAH/NO, or SAH/nimodipine. Glyceroltrinitrate (GTN) at 0.5 microg/microl (0.5 microl/h) or nimodipine at 0.2 microg/microl (10 microl/h) or NaCl was continuously infused into the cisterna magna via an Alzet osmotic pump from day 0 to day 5 after injection of 1.0 ml autologous blood. The magnitude of spasm in the basilar artery was determined by comparison of pre- and posttreatment angiography and was calculated as proportional change in intraluminal diameter based on automatic measurements.
  
  
  RESULTS
  A total of 55 experiments and 110 angiograms were performed. SAH was associated with vasoconstriction of the basilar artery (SAH/NaCl group 19.85+/-2.94%). Continuous intrathecal injection of GTN and nimodipine prevented SAH-induced CVS. There was significant prevention of CVS in animals treated with GTN (SAH/NO group 5.93+/-5.2%, n=11) and nimodipine (SAH/nimodipine group: 0.55+/-2.66%, n=9). There was no significant difference between the treatment groups and controls in prevention of CVS.
  
  
  CONCLUSIONS
  This study demonstrates that prophylactic continuous intrathecal administration of either GTN or nimodipine equally prevents SAH-associated CVS in an animal model.
authors.affiliation: Department of Intensive Care Medicine, University Hospital, Freiburgstrasse 10, 3010 Berne, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Marbacher
authors.forename: Volker
authors.initials: V
authors.lastname: Neuschmelting
authors.forename: Thilo
authors.initials: T
authors.lastname: Graupner
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
authors.forename: Javier
authors.initials: J
authors.lastname: Fandino
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000000981:diagnostic imaging; D002533:Cerebral Angiography; D005260:Female; D007278:Injections, Spinal; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage*; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D005996:Nitroglycerin / Q000008:administration & dosage*; D011817:Rabbits; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D014665:Vasodilator Agents / Q000008:administration & dosage*; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000517:prevention & control*
chemical_list: D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009553:Nimodipine; D005996:Nitroglycerin