TY - JOUR
T1 - Effect of vasodilation by milrinone, a phosphodiesterase III inhibitor, on vasospastic arteries after a subarachnoid hemorrhage in vitro and in vivo
T2 - Effectiveness of cisternal injection of milrinone
AU - Nishiguchi, Mitsuhisa
AU - Ono, Shigeki
AU - Iseda, Keiichi
AU - Manabe, Hiroaki
AU - Hishikawa, Tomohito
AU - Date, Isao
PY - 2010/1
Y1 - 2010/1
N2 - 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).
AB - 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).
KW - Canine model
KW - Intra-arterial injection
KW - Intracisternal injection
KW - Milrinone
KW - Vasospasm
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U2 - 10.1227/01.NEU.0000363153.62579.FF
DO - 10.1227/01.NEU.0000363153.62579.FF
M3 - Article
C2 - 20023546
AN - SCOPUS:77249090706
VL - 66
SP - 158
EP - 164
JO - Neurosurgery
JF - Neurosurgery
SN - 0148-396X
IS - 1
ER -