title: Suppression of pentylenetetrazol-elicited seizure activity by intraosseous propranolol in pigs.
abstract: The intraosseous (IO) route provides a rapid and effective alternative venous access in the pediatric population when the conventional intravenous (IV) route cannot be easily obtained. DL-propranolol, a beta-adrenoceptor antagonist, exhibits antiepileptic activity in various animal seizure models. This study assessed the efficacy of IO propranolol in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, ECG and electrocortical activity. Seizure activity was induced by pentylenetetrazol (PTZ; 100 mg/kg; IV). Sixty seconds after the onset of seizure activity, the animals either received no drug (control) or propranolol (IV or IO via an 18-gauge spinal needle placed in the right proximal tibia). A transient increase (16.3-50.0%) in the mean arterial blood pressure (MAP) was observed following PTZ administration. Both IO and IV propranolol significantly suppressed the seizure duration (SD) (sec/min interval) at 1 min following drug administration; SD control, 36.3 +/- 4.8; IV propranolol, 12.3 +/- 5.1; IO propranolol, 18.3 +/- 6.0. In addition, both IV and IO propranolol produced a maximal decrease of 32-38% in the basal heart rate; and reduced the transient increase in MAP elicited by PTZ, with no significant effect on the basal MAP. The data demonstrate that 1) propranolol possesses anticonvulsant activity against PTZ-induced seizure in the pig, and 2) the intraosseous route is a rapid and effective alternative venous access for propranolol administration in swine.
authors.affiliation: Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
authors.forename: K F
authors.initials: KF
authors.lastname: Jim
authors.forename: C M
authors.initials: CM
authors.lastname: Lathers
authors.forename: W H
authors.initials: WH
authors.lastname: Spivey
authors.forename: W D
authors.initials: WD
authors.lastname: Matthews
authors.forename: C
authors.initials: C
authors.lastname: Kahn
authors.forename: K
authors.initials: K
authors.lastname: Dolce
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001842:Bone and Bones; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D007275:Injections, Intravenous; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors
chemical_list: D011433:Propranolol; D010433:Pentylenetetrazole