ANTIOXIDANT DEPLETION, LIPID-PEROXIDATION, AND IMPAIRMENT OF CALCIUM-TRANSPORT INDUCED BY AIR-BLAST OVERPRESSURE IN RAT LUNGS

Exposure to blast overpressure, or the sudden rise in atmospheric pres sure after explosive detonation, results in damage mainly of the gas-f illed organs. In addition to the physical damage, in the lung, injury may proceed via a hemorrhage-dependent mechanism initiating oxidative stress and accumulation of lipid peroxidation products. Massive ruptur e of capillaries and red blood cells, release of hemoglobin, its oxida tion to met-hemoglobin and degradation sets the stage for heme-catalyz ed oxidations. The authors hypothesized that lipid hydroperoxides inte ract with met-hemoglobin in the lungs of exposed animals to produce fe rryl-hemoglobin, an extremely potent oxidant that induces oxidative da mage by depleting antioxidants and initiating peroxidation reactions. Oxidation-induced disturbance of Ca2+ homeostasis facilitates further amplification of the damage. To test this hypothesis, groups of anesth etized rats (6 rats/group) were exposed to blast at 3 peak pressures: low (61.2 kPa), medium (95.2 kPa), high (136 kPa). One group served as an unexposed control. Immediately after exposure, the rats were eutha nized and the lungs were analyzed for biochemical parameters. Blast ov erpressure caused: (1) depletion of total and water-soluble pulmonary antioxidant reserves and individual antioxidants (ascorbate, vitamin E , GSH), (2) accumulation of lipid peroxidation products (conjugated di enes, TBARS), and (3) inhibition of ATP-dependent Ca2+ transport. The magnitude of these changes in the lungs were proportional to the peak blast overpressure. Inhibition of Ca2+ transport strongly correlated w ith both depletion of antioxidants and enhancement of lipid peroxidati on. In model experiments, met-hemoglobin/H2O2 produced damage to Ca2transport in the lungs from control animals similar to that observed i n the lungs from blast overpressure-exposed animals. Ascorbate, which is known to reduce ferryl-hemoglobin, protected against met-hemoglobin /H2O2-induced damage of Ca2+ transport. If ferryl-hemoglobin is the ma jor reactive oxygen species released by hemorrhage, then its specific reductants (e.g., nitric oxide) along with other antioxidants may be b eneficial protectants against pulmonary barotrauma.