title: Studies of isolated global brain ischaemia: III. Influence of pulsatile flow during cerebral perfusion and its link to consistent full neurological recovery with controlled reperfusion following 30 min of global brain ischaemia.
abstract: OBJECTIVE
  Brain damage is universal in the rare survivor of unwitnessed cardiac arrest. Non-pulsatile-controlled cerebral reperfusion offsets this damage, but may simultaneously cause brain oedema when delivered at the required the high mean perfusion pressure. This study analyses pulsatile perfusion first in control pigs and then using controlled reperfusion after prolonged normothermic brain ischaemia (simulating unwitnessed arrest) to determine if it might provide a better method of delivery for brain reperfusion.
  
  
  METHODS
  Initial baseline studies during isolated brain perfusion in 12 pigs (six non-pulsatile and six pulsatile) examined high (750 cc/min) then low (450 cc/min) fixed flow before and after transient (30 s) ischaemia, while measuring brain vascular resistance and oxygen metabolism. Twelve subsequent pigs underwent 30 min of normothermic global brain ischaemia followed by either uncontrolled reperfusion with regular blood (n = 6) or pulsatile-controlled reperfusion (n = 6) before unclamping brain inflow vessels. Functional neurological deficit score (NDS; score: 0, normal; 500, brain death) was evaluated 24 h post-reperfusion.
  
  
  RESULTS
  High baseline flow rates with pulsatile and non-pulsatile perfusion before and after transient ischaemia maintained normal arterial pressures (90-100 mmHg), surface oxygen levels IN Vivo Optical Spectroscopy (INVOS) and oxygen uptake. In contrast, oxygen uptake fell after 30 s ischaemia at 450 cc/min non-pulsatile flow, but improved following pulsatile perfusion, despite its delivery at lower mean cerebral pressure. Uncontrolled (normal blood) reperfusion after 30 min of prolonged ischaemia, caused negligible INVOS O(2) uptake (<10-15%), raised conjugated dienes (CD; 1.75 ± 0.15 A(233 mn)), one early death, multiple seizures, high NDS (243 ± 16) and extensive cerebral infarcts (2,3,5-triphenyl tetrazolium chloride stain) and oedema (84.1 ± 0.6%). Conversely, pulsatile-controlled reperfusion pigs exhibited normal O(2) uptake, low CD levels (1.31 ± 0.07 A(233 mn); P < 0.01 versus uncontrolled reperfusion), no seizures and a low NDS (32 ± 14; P < 0.001 versus uncontrolled reperfusion); three showed complete recovery (NDS = 0) and all could sit and eat. Post-mortem brain oedema was minimal (81.1 ± 0.5; P < 0.001 versus uncontrolled reperfusion) and no infarctions occurred.
  
  
  CONCLUSIONS
  Pulsatile perfusion lowers cerebral vascular resistance and improves global O(2) uptake to potentially offset post-ischaemic oedema following high-pressure reperfusion. The irreversible functional and anatomic damage that followed uncontrolled reperfusion after a 30-min warm global brain ischaemia interval was reversed by pulsatile-controlled reperfusion, as its delivery resulted in consistent near complete neurological recovery and absent brain infarction.
authors.affiliation: Department of Surgery, University of California, Los Angeles, CA, USA. allen.brad@yahoo.com
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Allen
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ko
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Buckberg
authors.forename: Zhong
authors.initials: Z
authors.lastname: Tan
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism; D001926:Brain Death; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000150:complications; D010101:Oxygen Consumption / Q000502:physiology; D011673:Pulsatile Flow / Q000502:physiology; D015424:Reperfusion / Q000379:methods*; D015427:Reperfusion Injury / Q000150:complications / Q000517:prevention & control; D034421:Sus scrofa