PREVENTION OF CHRONIC CEREBRAL VASOSPASM IN DOGS WITH MILRINONE

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.