title: Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage.
abstract: Acute cerebral hypoperfusion following subarachnoid hemorrhage (SAH) is highly related to the pathogenesis of delayed cerebral ischemia (DCI), but the therapeutic option is poorly available. This study aimed to clarify the effect of milrinone (MIL) on cerebral blood flow (CBF) and related outcomes after experimental SAH.
  
  
  
  Twenty-seven male C57BL/6 mice were assigned to either sham surgery (SAH-sham; n=6), SAH induced by endovascular perforation (control; n=10), or SAH followed by cardiac support with intravenous MIL (n=11) performed 1.5-h after SAH induction. CBF, neurobehavioral function, occurrence of DCI were assessed by MR-continuous arterial spin labeling, daily neurological score testing, and diffusion- and T2-weighted MR images on days 1 and 3, respectively.
  
  
  
  Initial global CBF depression was notable in mice of control and MIL groups as compared to the SAH-sham group (P<0.05). MIL raised CBF in a dose-dependent manner (P<0.001), resulted in lower incidence of DCI (P=0.008) and better recovery from neurobehavioral decline than control (P<0.001). The CBF values on day 1 predicted DCI with a cut-off of 42.5ml/100g/min (82% specificity and 83% sensitivity), which was greater in mice treated with MIL than those of control (51.7 versus 37.6ml/100g/min; P<0.001).
  
  
  
  MIL improves post-SAH acute hypoperfusion that can lead to the prevention of DCI and functional worsening, acting as a neurocardiac protective agent against EBI.
authors.affiliation: Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan; Graduate School of Psychology, Kobe Shoin Women's University, Kobe, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mutoh
authors.affiliation: Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan; Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan. Electronic address: tmutoh@tiara.ocn.ne.jp.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Mutoh
authors.affiliation: Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan; Department of Preclinical Evaluation, IDAC, Tohoku University, Sendai, Japan.
authors.forename: Kazumasu
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan; Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tatewaki
authors.affiliation: Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Taki
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects*; D015150:Echocardiography, Doppler; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D020105:Milrinone / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D002316:Cardiotonic Agents; D018696:Neuroprotective Agents; D020105:Milrinone
keywords: Cardiac output; Cerebral blood flow; Delayed cerebral ischemia; Early brain injury; Milrinone; Mouse model; Subarachnoid hemorrhage