Document Detail


Studies of isolated global brain ischaemia: II. Controlled reperfusion provides complete neurologic recovery following 30 min of warm ischaemia - the importance of perfusion pressure.
MedLine Citation:
PMID:  22436245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Neurologic injury after sudden death is likely due to a reperfusion injury following prolonged brain ischaemia, and remains problematic, especially if the cardiac arrest is unwitnessed. This study applies a newly developed isolated model of global brain ischaemia (simulating unwitnessed sudden death) for 30 min to determine if controlled reperfusion permits neurologic recovery.
METHODS: Among the 17 pigs undergoing 30 min of normothermic global brain ischaemia, 6 received uncontrolled reperfusion with regular blood (n = 6), and 11 were reperfused for 20 min with a warm controlled blood reperfusate containing hypocalcaemia, hyper-magnesemia, alkalosis, hyperosmolarty and other constituents that were passed through a white blood cell filter and delivered at flow rates of 350 cc/min (n = 3), 550 cc/min (n = 2) or 750 cc/min (n = 6). Neurologic deficit score (NDS) evaluated brain function (score 0 = normal, 500 = brain death) 24 h post-reperfusion and 2,3,5-triphenyltetrazolium chloride (TTC) staining determined brain infarction.
RESULTS: Regular blood (uncontrolled) reperfusion caused negligible brain O(2) uptake by IN Vivo Optical Spectroscopy (INVOS) (<10-15% O(2) extraction), oxidant damage demonstrated by raised conjugated diene (CD) levels (1.78 ± 0.13 A233 mn), multiple seizures, 1 early death from brain herniation, high NDS (249 ± 39) in survivors, brain oedema (84.4 ± 0.6%) and extensive cerebral infarctions. Conversely, controlled reperfusion restored surface brain oxygen saturation by INVOS to normal (55-70%), but the extent of neurologic recovery was determined by the brain reperfusion pressure. Low pressure reperfusion (independent of flow) produced the same adverse functional, metabolic and anatomic changes that followed uncontrolled reperfusion in seven pigs (three at 350 cc/min, two at 550 and two at 750 cc/min). Conversely, higher reperfusion pressure in four pigs (all at 750 cc/min) resulted in NDS of 0-70* indicating complete (n = 2) or near complete (n = 2) neurological recovery, negligible CDs production (1.29 ± 0.06 A233mn)*, minimal brain oedema (80.6 ± 0.2%)* and no infarction by TTC stain.
CONCLUSIONS: Brain injury can be avoided after 30 min of normothermic cerebral ischaemia if controlled reperfusion pressure is >50 mmHg, but the lower pressure (<50 mmHg) controlled reperfusion that is useful in other organs cannot be transferred to the brain. Moreover, INVOS is a poor guide to the adequacy of cerebral perfusion and the capacity of controlled brain reperfusion to restore neurological recovery. *P < 0.001 versus uncontrolled or low pressure controlled reperfusion.
Authors:
Bradley S Allen; Yoshihiro Ko; Gerald D Buckberg; Zhong Tan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-20
Journal Detail:
Title:  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery     Volume:  41     ISSN:  1873-734X     ISO Abbreviation:  Eur J Cardiothorac Surg     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-18     Completed Date:  2012-07-17     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1147-54     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of California, Los Angeles, CA, USA. allen.brad@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology
Brain / metabolism
Brain Death
Brain Ischemia / etiology,  physiopathology,  therapy*
Cerebrovascular Circulation / physiology
Disease Models, Animal
Heart Arrest / complications
Oxygen Consumption / physiology
Reperfusion / methods*
Reperfusion Injury / complications,  prevention & control
Sus scrofa
Warm Ischemia / adverse effects*
Grant Support
ID/Acronym/Agency:
R01-HL-71729-04/HL/NHLBI NIH HHS
Comments/Corrections
Comment In:
Eur J Cardiothorac Surg. 2012 May;41(5):1163-5   [PMID:  22511800 ]

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