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.
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).
Nishiguchi
Mitsuhisa
M
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
Ono
Shigeki
S
Iseda
Keiichi
K
Manabe
Hiroaki
H
Hishikawa
Tomohito
T
Date
Isao
I
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
D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D020105:Milrinone