[Effect of opening of neuronal mitochondrial permeability transition pore on respiratory function after cardiopulmonary resuscitation in rats].
OBJECTIVE
To investigate the effect of opening of neuronal mitochondrial permeability transition pore (MPTP) on respiratory function after cardiopulmonary resuscitation (CPR) in rats and its possible mechanism.


METHODS
Cardiac arrest (CA)/CPR rat model was reproduced by asphyxiation and ice-cold KCl followed resuscitation and restoration of spontaneous circulation (ROSC). The rats were sacrificed by decapitation at 3, 6, 12, 24, 48 and 72 hours. Isolation of brain cortex neuronal mitochondria was processed. MPTP opening degree was examined by spectrophotometer. Clark oxygen electrode was used to measure mitochondrial respiratory function: the mitochondrial ultra structure was examined with transmission electron microscope (TEM).


RESULTS
Mitochondrial respiratory function was severely injured after CA/CPR. Mitochondrial respiratory state III (R3) was decreased. Neural cell MPTP opened persistently after ROSC. The opening degree of MPTP did not reach the peak instantly, and its change depended on time. It remained at a low level within 6 hours after ROSC, then rapidly opened, reaching the maximal degree at 12 hours, but it became smaller at 24 hours. At 48 hours the degree of opening became larger again, but shrank once more at 72 hours. However, it did not reach the normal level (all P<0.05). Although R3 was decreased, mitochondrial respiratory state IV (R4) was increased, meanwhile the respiratory control rate (RCR) and P/O ratio descended markedly. They maintained at low levels along with the elapse of time (P<0.05 or P<0.01). TEM revealed obvious injury to neurons. Correlation analysis showed that the MPTP opening degree and RCR was obviously positively correlated (r=0.025, P<0.05).


CONCLUSIONS
The opening of MPTP is the main cause of aggravation of energy metabolism disturbance of neural cells after CPR. To take measures to inhibit the opening of MPTP within 12 hours after ROSC may promote improvement of neuronal mitochondrial function, and it might help win the chances for neural function to recover.
Ma
Yu-jie
YJ
Intensive Care Unit, General Air Force Hospital, PLA, Beijing 100036, China. yujma@126.com
Yang
Xing-yi
XY
Lin
Zhao-fen
ZF
Miao
Ming-yong
MY
Zhang
Lei
L
Ning
Bo
B
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D016887:Cardiopulmonary Resuscitation; D002478:Cells, Cultured; D008297:Male; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore