BACKGROUND: Synaptic dysfunction is critical in irreversible brain damage. Synapses are enriched in docosahexaenoic acid (DHA, 22:6). Here we tested the hypothesis that a) polyunsaturated fatty acid peroxidation is a marker of irreversible damage; and b) high-dose HBO may be neuroprotective by decreasing lipid peroxidation. We have previously shown that high-dose HBO favorably promotes return of spontaneous circulation (ROS) after a prolonged 25-minute cardiopulmonary arrest in an open chest porcine model (Ann. Emerg Med., 1999). Initial ROS was defined as mean arterial pressure (MAP) ≥75 mmHg and sustained ROS as MAP ≥50 mmHg. Based upon the physiologic parameter of initial and sustained ROS, the results were significant (2-tailed Fisher's exact test, p ≤0.0049).
MATERIALS AND METHODS: Two hrs after initiation of Advanced Cardiac Life Support, each animal was sacrificed and brain harvested. Brain tissue was immediately frozen in liquid nitrogen and stored in a -80°C freezer. Lipid peroxidation was quantitated using the thiobarbituric acid assay. Results were significant using a 2-tailed Student's T-Test
RESULTS:
|
Oxygen Ventilation Environment
|
Group 1, (n=6) 4 ATM abs
|
Group 2, (n=6) 2 ATM abs
|
Group 3, (n=6) 1 ATM abs
|
|
Initial ROS MAP ≥75 mmHg
|
5/6
|
0/6
|
0/6
|
|
Intact ROS @ 2 hrs Sustained MAP ≥50 mmHg
|
4/6
|
0/6
|
0/6
|
|
Umoles Malonaldehyde/ug protein
|
80±64
|
126±71
|
100±46
|
|
Intact ROS@ 2 hrs sustained MAP≥
|
44±33
|
P≤0.032
|
P≤ 0.043
|
CONCLUSIONS: Lipid peroxidation reflects pathophysiological responses and recovery. HBO in high dose (4 ATM abs) compared to low dose (2 ATM abs) or normobaric (1 ATM abs) may confer neuroprotection by attenuating reperfusion-induced brain lipid peroxidation after resuscitation from prolonged 25-minute cardiopulmonary arrest. Neuroprotection by high-dose HBO may involve decreasing synaptic membrane lipid peroxidation, among other events.
