title: Effect of vasodilation by milrinone, a phosphodiesterase III inhibitor, on vasospastic arteries after a subarachnoid hemorrhage in vitro and in vivo: effectiveness of cisternal injection of milrinone.
abstract: OBJECTIVE
  Cerebral vasospasm remains a major cause of morbidity and mortality. Milrinone, a bipyridine phosphodiesterase III inhibitor, is a potent member of the inodilator class of cardiac agents for vasospasm and is injected intra-arterially or intracisternally. There have been no studies investigating the duration of action (context-sensitive half-life) of milrinone for vasospasm or the most effective route of administration (intra-arterial versus intracisternal). We examined the effects of intracisternal and intra-arterial injection of milrinone on chronic cerebral vasospasm in dogs.
  
  
  METHODS
  A double-hemorrhage canine model was used. In a preliminary isometric tension study of canine vasospastic basilar arteries, the vasodilatory effects of milrinone were examined 7 days after an initial injection of blood. Milrinone was injected intracisternally (0.1 mg, 0.47 mmol/L) or intra-arterially (0.3 mg/kg, 1.2 mmol/L), and angiograms were performed 30, 60, 120, 180, 240, 300, and 360 minutes later on day 7.
  
  
  RESULTS
  Milrinone produced concentration-dependent vasodilation and was effective intracisternally, resulting in significant dilation until 180 minutes after injection and a tendency for dilation until 240 minutes. The effect of intra-arterial injection was not as significant compared with an intracisternal injection, resulting in significant dilation only at 180 minutes after intra-arterial injection.
  
  
  CONCLUSIONS
  Intracisternal injection of milrinone was more effective than intra-arterial injection for chronic cerebral vasospasm in dogs because intracisternal injection produced a higher concentration in vasospastic arteries (0.034-0.068 mmol/L intracisternally versus 0.016 mmol/L intra-arterially).
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Japan. nisiguti@iwakuni-nh.go.jp
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Nishiguchi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ono
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iseda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Manabe
authors.forename: Tomohito
authors.initials: T
authors.lastname: Hishikawa
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D000792:Angiography / Q000379:methods; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007269:Injections, Intra-Arterial / Q000379:methods; D008297:Male; D020105:Milrinone / Q000494:pharmacology / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000662:veterinary; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000662:veterinary
chemical_list: D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D020105:Milrinone