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Aging and disease    2020, Vol. 11 Issue (6) : 1527-1536     DOI: 10.14336/AD.2020.0325
Review Article |
Intra-arterial Cold Saline Infusion in Stroke: Historical Evolution and Future Prospects
Longfei Wu1, Mitchell Huber2, Di Wu1, Jian Chen3, Ming Li1, Yuchuan Ding4, Xunming Ji3,*
1Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.
2Department of Emergency Medicine, Ascension St. John Hospital, Detroit, MI, USA.
3Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
4Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
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Abstract  

Acute ischemic stroke (AIS) is a perpetual threat to life and functionality due to its high morbidity and mortality. In the past several decades, therapeutic hypothermia has garnered interest as an effective neuroprotective method in the setting of AIS. However, traditional hypothermic methods have been criticized for their low cooling efficiency and side effects. Intra-arterial cold saline infusion (IA-CSI), as a novel hypothermic method, not only minimizes these side effects, but is also perfectly integrated with widely accepted recanalization modalities in AIS, thereby serving as a promising prospect for clinical translation. In this article, we review the historical development of IA-CSI, summarize major studies of IA-CSI in rodents, large animals, and humans to date, and suggest insight into future development prospects in the field of AIS. We hope that this article will provide inspiration for the future application of hypothermia in AIS patients.

Keywords stroke      neuroprotection      hypothermia      intra-arterial cold saline infusion      clinical translation     
Corresponding Authors: Ji Xunming   
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These authors contrinuted equally to this work.

Just Accepted Date: 28 March 2020   Issue Date: 19 November 2020
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Wu Longfei
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Cite this article:   
Wu Longfei,Huber Mitchell,Wu Di, et al. Intra-arterial Cold Saline Infusion in Stroke: Historical Evolution and Future Prospects[J]. Aging and disease, 2020, 11(6): 1527-1536.
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http://www.aginganddisease.org/EN/10.14336/AD.2020.0325     OR
AuthorsSubjectModelInfusateInfusion rateInfusion durationInfusion volumeTime to target tempBrain tempCore body tempInfarct volumeFunctional outcome
Rodent studies
Ding et al., 2002 [29]RattMCAOSaline 23 °C2 ml/min3-4 min7 ml3-4 min32-33 °CNot mentionedReducedImproved
Saline 37 °C2 ml/min3-4 min7 ml-37 °CNot mentionedReducedImproved
Ding et al., 2002 [30]RattMCAOSaline and heparin 23 °C3 ml/min3-4 min8-10 ml4 min32-33 °CUnchangedReducedImproved
Ding et al., 2003 [34]RattMCAOSaline 37 °C2 ml/min3 min6 ml-Not mentionedNot mentionedNot mentionedNot mentioned
Ding et al., 2004 [35]RattMCAOSaline 37 °C2 ml/min3 min6 ml-Not mentionedNot mentionedNot mentionedNot mentioned
Ding et al., 2004 [33]RattMCAOSaline 20 °C0.6 ml/min10 min6 ml< 5 minCortex 33.4 °C
Striatum 33.9 °C
> 36 °CReducedImproved
Kurisu et al., 2016 [36]RattMCAOSaline 10 °C0.32-0.41 ml/min15 min4.8-6.2 ml< 5 minCortex 34.8 °C
Striatum 35.4 °C
> 37 °CReducedImproved
Li et al., 2004 [37]RattMCAOSaline 20 °C0.6 ml/min10 min6 mlNot mentionedNot mentionedNot mentionedReducedImproved
Luan et al., 2004 [38]RattMCAOSaline 20 °C0.6 ml/min10 min6 ml< 5 minCortex 33.4 °C
Striatum 33.9 °C
> 36 °CNot mentionedNot mentioned
Zhao et al., 2009 [39]RattMCAOSaline 20 °C0.6 ml/min10 min6 ml< 10 minCortex 32.8-33.2 °C
Striatum 33.2-33.3 °C
> 37 °CReducedImproved
Ji et al., 2012 [70]RattMCAOSaline 10 °C0.25 ml/min30 min
10/10/10 min
7.5 ml6 min34.6 °C37 °CReducedUnchanged
Ji et al., 2012 [71]RattMCAOSaline 10 °C0.17-0.42 ml/min20 minNot mentionedNot mentioned33-34 °C37 °CReducedImproved
Kurisu et al., 2016 [42]RatpMCAOSaline 4 °C0.28-0.37 ml/min15 min4.2-5.6 ml< 5 minCortex 32.5 °C
Striatum 34.3 °C
> 37 °CReducedImproved
Song et al., 2013 [45]RattMCAOMagnesium sulfate 15 °C0.4 ml/min20 min8 ml5-10 min33-34 °C37 °CReducedImproved
Chen et al., 2013 [46]RattMCAOHuman albumin 0 °CNot mentionedNot mentionedNot mentioned< 3 minCortex 30.5 °C
Striatum 30.8 °C
37-37.5 °CReducedImproved
Wu et al., 2017 [47]RattMCAOSaline 20 °C plus DHC0.6 ml/min10 min6 min< 10 min< 35 °C35 °CReducedImproved
Wu et al., 2019 [48]RattMCAOSaline 4 °C plus DHC0.6 ml/min10 min6 mlNot mentionedNot mentionedNot mentionedReducedImproved
Wei et al., 2019 [49]RattMCAOSaline 4 °C plus MSC0.6 ml/min5 min3 mlNot mentionedNot mentionedNot mentionedReducedImproved
Large animal studies
Furuse et al., 2007 [51]Canine-Ringer’s solution 6.5 °C38.9-43.4 ml/min30 min> 1000 ml30 min33.6 °C34.1 °C--
Wang et al., 2016 [52]Rhesus monkey-Ringer’s solution 0-4 °C5 ml/min20 min100 ml10 minCortex 34 °C
Striatum 33.9 °C
37.1 °C--
Mattingly et al., 2016 [57]SwinetMCAONot mentionedNot mentioned36-150 minNot mentioned< 30 min26 °C34 °CReducedNot mentioned
Caroff et al., 2019 [53]Canine-Saline 4.5 °C20-40 ml/min14.4 min515 ml< 5 min23.8 °C37.2 °C--
tMCAOSaline 4.5 °C22 ml/min25 min550 ml< 5 min31-32 °C37.2 °CReducedImproved
Clinical studies
Choi et al., 2010 [58]Non-stroke patients-Saline 4-17 °C33 ml/min10 min330 ml< 10 min-0.84 °C (JVBT)-0.15 °C--
Chen et al., 2016 [62]AIS patients-Saline 4 °C10 ml/min (IBR)
30 ml/min (IAR)
5 min (IBR)
10 min (IAR)
350 mlNot mentioned-2 °C-0.1 °C--
Wu et al., 2018 [63]AIS patients-Saline 4 °C10 ml/min (IBR)
30 ml/min (IAR)
5 min (IBR)
10 min (IAR)
350 mlNot mentionedNot mentioned36.5 °CReducedUnchanged
Table 1  Summary of studies on intra-arterial cold saline infusion.
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