PMID- 28008646
OWN - NLM
STAT- MEDLINE
DCOM- 20170710
LR  - 20170713
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 44
IP  - 4
DP  - 2017 Apr
TI  - Acute cardiac support with intravenous milrinone promotes recovery from early 
      brain injury in a murine model of severe subarachnoid haemorrhage.
PG  - 463-469
LID - 10.1111/1440-1681.12718 [doi]
AB  - Early brain injury/ischaemia (EBI) is a serious complication early after 
      subarachnoid haemorrhage (SAH) that contributes to development of delayed 
      cerebral ischaemia (DCI). This study aimed to determine the role of inotropic 
      cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion 
      attributable to EBI and improving outcomes after experimental SAH. Forty-three 
      male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by 
      endovascular perforation plus postconditioning with 2% isoflurane (Control), or 
      SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor 
      inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL 
      infusion (0.25-0.75 mug/kg/min) between 1.5 and 2.5 hours after SAH induction was 
      monitored with Doppler echocardiography. Magnetic resonance imaging 
      (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood 
      flow (CBF) measurements. Neurobehavioral function was assessed daily by 
      neurological score and open field test. DCI was analyzed 3 days later by 
      determining infarction on MRI. Mild reduction of cardiac output (CO) and global 
      cerebral blood flow (CBF) depression were notable early after SAH. MIL increased 
      CO in a dose-dependent manner (P<.001), which was accompanied by improved 
      hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The 
      neuroprotective effects afforded by MIL or Control were attenuated by 
      hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL 
      improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral 
      improvement in mice after severe SAH, in which HIF may be acting as a critical 
      mediator.
CI  - (c) 2017 John Wiley & Sons Australia, Ltd.
FAU - Mutoh, Tomoko
AU  - Mutoh T
AD  - Department of Nuclear Medicine and Radiology, Institute of Development, Aging and 
      Cancer, Tohoku University, Sendai, Japan.
AD  - Graduate School of Psychology, Kobe Shoin Women's University, Kobe, Japan.
FAU - Mutoh, Tatsushi
AU  - Mutoh T
AUID- ORCID: 0000-0001-7770-379X
AD  - Department of Nuclear Medicine and Radiology, Institute of Development, Aging and 
      Cancer, Tohoku University, Sendai, Japan.
AD  - Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan.
FAU - Nakamura, Kazuhiro
AU  - Nakamura K
AD  - Department of Nuclear Medicine and Radiology, Institute of Development, Aging and 
      Cancer, Tohoku University, Sendai, Japan.
AD  - Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan.
FAU - Yamamoto, Yukiko
AU  - Yamamoto Y
AD  - Primetech Life Science Laboratory, Tokyo, Japan.
FAU - Tsuru, Yoshiharu
AU  - Tsuru Y
AD  - Primetech Life Science Laboratory, Tokyo, Japan.
FAU - Tsubone, Hirokazu
AU  - Tsubone H
AD  - Graduate School of Agricultural and Life Sciences, The University of Tokyo, 
      Tokyo, Japan.
FAU - Ishikawa, Tatsuya
AU  - Ishikawa T
AD  - Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan.
FAU - Taki, Yasuyuki
AU  - Taki Y
AD  - Department of Nuclear Medicine and Radiology, Institute of Development, Aging and 
      Cancer, Tohoku University, Sendai, Japan.
LA  - eng
PT  - Journal Article
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - JU9YAX04C7 (Milrinone)
SB  - IM
MH  - Administration, Intravenous
MH  - Animals
MH  - Brain Injuries/*complications
MH  - Brain Ischemia/complications
MH  - Cerebrovascular Circulation/drug effects
MH  - Disease Models, Animal
MH  - Hemodynamics/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Milrinone/*administration & dosage/*pharmacology/therapeutic use
MH  - Recovery of Function/*drug effects
MH  - Subarachnoid Hemorrhage/complications/*drug therapy/*physiopathology
OTO - NOTNLM
OT  - cardiac output
OT  - cerebral blood flow
OT  - delayed cerebral ischaemia
OT  - early brain injury
OT  - milrione
OT  - mouse model
OT  - neurobehavioral outcome
OT  - subarachnoid haemorrhage
EDAT- 2016/12/23 06:00
MHDA- 2017/07/14 06:00
CRDT- 2016/12/24 06:00
PHST- 2016/10/30 00:00 [received]
PHST- 2016/12/14 00:00 [revised]
PHST- 2016/12/19 00:00 [accepted]
PHST- 2016/12/23 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/12/24 06:00 [entrez]
AID - 10.1111/1440-1681.12718 [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2017 Apr;44(4):463-469. doi: 10.1111/1440-1681.12718.