Hypoxemic reperfusion exacerbates the neurological injury sustained during neonatal deep hypothermic circulatory arrest: a model of cyanotic surgical repair.
OBJECTIVE
Deep hypothermic circulatory arrest (DHCA) is frequently used in infants undergoing the Norwood procedure. These infants are necessarily hypoxemic after separation from CPB. Considerable energy has been spent characterizing the physiological and histological consequences of DHCA, but these have largely focused on a normoxemic period of reperfusion. Furthermore, evidence has accumulated to suggest that the cerebral vascular autoregulatory mechanisms are dysfunctional following DHCA. In particular, the vasodilatation that elevates cerebral blood flow (CBF) in response to hypoxemia is absent. This study therefore aimed to investigate whether post-CPB hypoxemia exacerbates brain injury resulting from DHCA.


METHODS
Twelve neonatal piglets were subjected to 2h DHCA and then separated from CPB. They were then randomized to either: Group 1, normoxic ventilation (n=5); or Group 2, hypoxemia (n=7), in which the arterial PaO(2) was reduced to 40-50 mmHg for the duration of reperfusion. Following a 20 h period of warm reperfusion, the animals were perfusion fixed and the brain analyzed for histological evidence of injury. Nine additional animals were studied in one of three control groups.


RESULTS
All animals survived the protocol. Post-operative parameters - including mean arterial pressure, acid-base status, inotrope requirements and arterial PaCO(2) - were similar. None of the control animals had any evidence of ischemia. Group 1 animals had moderate injury (total score 7.4+/-1.6). In Group 2, three animals sustained irretrievable brain injury evidenced by gross edema and early liquefactive necrosis. The remaining four had severe ischemic histological changes (score 14.5+/-1.6, p<0.03).


CONCLUSIONS
Hypoxemic reperfusion after prolonged DHCA results in increased neuronal loss. The use of DHCA for staged palliation may confer disproportionately greater cerebral risk than other patient groups. Alternatively, methods to augment oxygen delivery - such as by ECMO - may be of particular benefit in the early re-perfusion window.
Hickey
Edward J
EJ
Oregon Health Science University, Portland, Oregon, USA. edward.hickey@sickkids.ca
You
Xiaomang
X
Kaimaktchiev
Vassil
V
Ungerleider
Ross M
RM
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000502:physiology; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects* / Q000379:methods; D004195:Disease Models, Animal; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D008856:Microscopy, Fluorescence / Q000379:methods; D015425:Myocardial Reperfusion / Q000009:adverse effects; D013552:Swine