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

Mitsuhisa Nishiguchi, Shigeki Ono, Keiichi Iseda, Hiroaki Manabe, Tomohito Hishikawa, Isao Date

Research output: Contribution to journalArticle

21 Citations (Scopus)

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. CONCLUSION: 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).

Original languageEnglish
Pages (from-to)158-164
Number of pages7
JournalNeurosurgery
Volume66
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Canine model
  • Intra-arterial injection
  • Intracisternal injection
  • Milrinone
  • Vasospasm

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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