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Prevention of chronic cerebral vasospasm in dogs with milrinone.

Publication ,  Journal Article
Khajavi, K; Ayzman, I; Shearer, D; Jones, SC; Levy, JH; Prayson, RA; Skibinski, CI; Hahn, JF; Chyatte, D
Published in: Neurosurgery
February 1997

OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of morbidity and death in patients with aneurysmal subarachnoid hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a powerful inotrope and vasodilator, but it has little effect on heart rate or blood pressure. Because of these properties, milrinone is an attractive potential therapy after subarachnoid hemorrhage. The purpose of the present study was to investigate the effect of milrinone on chronic experimental cerebral vasospasm. METHODS: A double-hemorrhage canine model of vasospasm was used to study the efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were compared in a treatment group of animals that received a loading dose of milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05 microgram/kg/min) milrinone pellets (n = 10) and a control group that received placebo pellets (n = 9), over an 8-day period after the initial subarachnoid hemorrhage. The hemorrhage was created by injection of 4 ml of autologous, nonheparinized, arterial blood into the cisterna magna on Days 1 and 3. Hemodynamic measurements, including cardiac output determinations, were made on Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS: Treatment with milrinone caused no significant changes in systemic hemodynamics. Angiographic vasospasm, however, was significantly reduced in the Day 8 angiograms 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 preventing chronic cerebral vasospasm in a canine model of experimental chronic cerebral vasospasm. This effect is independent of changes in systemic hemodynamics. Milrinone and related drugs warrant further investigation for the treatment of cerebral vasospasm.

Duke Scholars

Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

February 1997

Volume

40

Issue

2

Start / End Page

354 / 362

Location

United States

Related Subject Headings

  • Vasodilator Agents
  • Subarachnoid Hemorrhage
  • Pyridones
  • Phosphodiesterase Inhibitors
  • Neurology & Neurosurgery
  • Milrinone
  • Ischemic Attack, Transient
  • Hemodynamics
  • Dogs
  • Cerebral Angiography
 

Citation

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Khajavi, K., Ayzman, I., Shearer, D., Jones, S. C., Levy, J. H., Prayson, R. A., … Chyatte, D. (1997). Prevention of chronic cerebral vasospasm in dogs with milrinone. Neurosurgery, 40(2), 354–362. https://doi.org/10.1097/00006123-199702000-00025
Khajavi, K., I. Ayzman, D. Shearer, S. C. Jones, J. H. Levy, R. A. Prayson, C. I. Skibinski, J. F. Hahn, and D. Chyatte. “Prevention of chronic cerebral vasospasm in dogs with milrinone.Neurosurgery 40, no. 2 (February 1997): 354–62. https://doi.org/10.1097/00006123-199702000-00025.
Khajavi K, Ayzman I, Shearer D, Jones SC, Levy JH, Prayson RA, et al. Prevention of chronic cerebral vasospasm in dogs with milrinone. Neurosurgery. 1997 Feb;40(2):354–62.
Khajavi, K., et al. “Prevention of chronic cerebral vasospasm in dogs with milrinone.Neurosurgery, vol. 40, no. 2, Feb. 1997, pp. 354–62. Pubmed, doi:10.1097/00006123-199702000-00025.
Khajavi K, Ayzman I, Shearer D, Jones SC, Levy JH, Prayson RA, Skibinski CI, Hahn JF, Chyatte D. Prevention of chronic cerebral vasospasm in dogs with milrinone. Neurosurgery. 1997 Feb;40(2):354–362.
Journal cover image

Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

February 1997

Volume

40

Issue

2

Start / End Page

354 / 362

Location

United States

Related Subject Headings

  • Vasodilator Agents
  • Subarachnoid Hemorrhage
  • Pyridones
  • Phosphodiesterase Inhibitors
  • Neurology & Neurosurgery
  • Milrinone
  • Ischemic Attack, Transient
  • Hemodynamics
  • Dogs
  • Cerebral Angiography