Protection against blast-induced mortality in rats by hemin.
BACKGROUND
A critical immediate determinant of survival after exposure to blast overpressure (BOP) is cardiovascular and respiratory impairment related to disruption of the alveolar septa and pulmonary capillaries and resulting in acute pulmonary hemorrhage. Hemoglobin (Hb) released from red cells can contribute to lethality by activation of oxidative stress reactions and severe vasoconstriction associated with hypoperfusion in the pulmonary microcirculation. Heme oxygenase-1 (HO-1) is activated by hemin, a product of Hb degradation and may confer protection against hemoglobin-mediated oxidative cell and tissue damage.


METHODS
Rats were injected intraperitoneally with hemin (50 mg/kg) or phosphate buffered saline (PBS). Twenty hours later, animals were placed in a shock tube and exposed to blast overpressure with mean intensity of approximately 160 kPa. Nonblasted sham-injected animals served as controls.


RESULTS
HO-1 mRNA and HO-1 protein in lungs was induced by injection of hemin. Exposure to blast resulted in confluent lung hemorrhage and mortality ( approximately 65%). Hemin injection significantly improved the survival rate of animals compared with PBS injected animals (p = 0.01).


CONCLUSIONS
The protection by hemin against blast may involve antioxidative and vasodilatory effects of HO-1, although, the precise mechanisms of the protection are unknown.
Chavko
Mikulas
M
Trauma and Resuscitative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland, USA. mikulas.chavko@med.navy.mil
Prusaczyk
W Keith
WK
McCarron
Richard M
RM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001753:Blast Injuries / Q000150:complications / Q000401:mortality* / Q000517:prevention & control*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000494:pharmacology*; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology*; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D008168:Lung / Q000187:drug effects; D055370:Lung Injury / Q000209:etiology / Q000517:prevention & control; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D000975:Antioxidants; D014665:Vasodilator Agents; D006427:Hemin; D051547:Heme Oxygenase-1