Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys.
OBJECTIVE
Hypothermia has shown promise as a neuroprotective strategy for stroke. The use of whole body hypothermia has limited clinical utility due to many severe side effects. Selective brain cooling, or local brain hypothermia, has been previously proposed as an alternative treatment strategy. This study investigated the safety, feasibility, and efficacy of selective brain hypothermia induced by local infusion of ice-cold lactated Ringer's solution in rhesus monkeys.


METHODS
Eight male rhesus monkeys were used in this study. Brain temperature in the territory supplied by middle cerebral artery (MCA) was reduced by infusing 100 mL of ice-cold (0 °C) lactated Ringer's solution over 20 min via a micro-catheter placed in the proximal MCA (n = 4). Vital signs and the temperature of the brain and rectum were monitored before and after infusion. Transcranial Doppler, Magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) were used to evaluate cerebral blood flow, cerebrovascular reactivity (CVR), cerebral edema, and vasospasm. Another cohort of rhesus monkeys (n = 4) were used as systemic cooling controls.


RESULTS
Oxygen saturation, blood pressure, heart rate, and hematologic analysis of the two groups remained within the normal range after infusion. Mild cerebral hypothermia (<35 °C) was achieved in 10 min (0.3 °C/min) and was maintained for 20 min in local cortex and striatum following local infusion. The average lowest cerebral temperature in the locally cooled animals was 33.9 ± 0.3 °C in the striatum following 20-min infusion. This was not observed in animals cooled by systemic infusion. The decreases in the rectal temperature for local and systemic infusion were 0.5 ± 0.2 °C and 0.5 ± 0.3 °C, respectively. Selective brain cooling did not cause any cerebral edema as determined by MRI or vasospasm in the perfused vessel based on DSA. Selective cerebral hypothermia did not significantly alter CVR.


CONCLUSIONS
Local infusion of ice-cold lactated Ringer's solution via micro-catheter is a safe and effective method for selective cerebral hypothermia. This cooling method could potentially be developed as a new treatment in acute ischemic stroke.
a China-America Institute of Neuroscience , XuanWu Hospital, Capital Medical University , Beijing , China.
Bincheng
B
Wang
a China-America Institute of Neuroscience , XuanWu Hospital, Capital Medical University , Beijing , China.
Di
D
Wu
b Department of Neurological Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA.
David
D
Dornbos Iii
a China-America Institute of Neuroscience , XuanWu Hospital, Capital Medical University , Beijing , China.
Jingfei
J
Shi
c Department of Anesthesiology , XuanWu Hospital, Capital Medical University , Beijing , China.
Yanhui
Y
Ma
d Department of Radiology , XuanWu Hospital, Capital Medical University , Beijing , China.
Mo
M
Zhang
e Department of Vascular Ultrasonography , XuanWu Hospital, Capital Medical University , Beijing , China.
Yumei
Y
Liu
f Department of Neurosurgery , XuanWu Hospital, Capital Medical University , Beijing , China.
Jian
J
Chen
g Department of Neurological Surgery , Wayne State University School of Medicine , Detroit , MI , USA.
Yuchuan
Y
Ding
a China-America Institute of Neuroscience , XuanWu Hospital, Capital Medical University , Beijing , China.
Yinghao
Y
Luo
a China-America Institute of Neuroscience , XuanWu Hospital, Capital Medical University , Beijing , China.|f Department of Neurosurgery , XuanWu Hospital, Capital Medical University , Beijing , China.
Xunming
X
Ji
D000704:Analysis of Variance; D015901:Angiography, Digital Subtraction; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003080:Cold Temperature; D004195:Disease Models, Animal; D005240:Feasibility Studies; D007036:Hypothermia, Induced / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D007552:Isotonic Solutions / Q000008:administration & dosage*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D009460:Neurologic Examination; D000077325:Ringer's Lactate; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial
D007552:Isotonic Solutions; D000077325:Ringer's Lactate
Digital subtraction angiography (DSA); Magnetic resonance imaging; Middle cerebral artery (MCA); Selective hypothermia; Transcranial Doppler (TCD)