OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a maj
or cause of morbidity and death in patients with aneurysmal subarachno
id hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine
monophosphate-specific phosphodiesterase enzyme in both cardiac and v
ascular smooth muscle, is a powerful inotrope and vasodilator, but it
has little effect on heart rate or blood pressure. Because of these pr
operties, milrinone is an attractive potential therapy after subarachn
oid hemorrhage. The purpose of the present study was to investigate th
e effect of milrinone on chronic experimental cerebral vasospasm. METH
ODS: A double-hemorrhage canine model of vasospasm was used to study t
he efficacy of milrinone. Angiographic vasospasm and systemic hemodyna
mics were compared in a treatment group of animals that received a loa
ding dose of milrinone (0.05 mg/kg, intravenously) and then slow-relea
se (0.05 mu g/kg/min) milrinone pellets (n = 10) and a control group t
hat received placebo pellets (n = 9), over an 8-day period after the i
nitial subarachnoid hemorrhage. The hemorrhage was created by injectio
n of 4 ml of autologous, nonheparinized, arterial blood into the ciste
rna magna on Days 1 and 3. Hemodynamic measurements, including cardiac
output determinations, were made on Days 0, 1, 3, 6, and 8 with a pul
monary artery catheter, and angiographic vasospasm was assessed on Day
8 by comparison with baseline angiograms. RESULTS: Treatment with mil
rinone caused no significant changes in systemic hemodynamics. Angiogr
aphic vasospasm, however, was significantly reduced in the Day 8 angio
grams for the treated group, compared with the control group (98.28 +/
- 14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area,
respectively; P < 0.001). CONCLUSION: Milrinone is effective in preven
ting chronic cerebral vasospasm in a canine model of experimental chro
nic cerebral vasospasm. This effect is independent of changes in syste
mic hemodynamics. Milrinone and related drugs warrant further investig
ation for the treatment of cerebral vasospasm.