Age-related mechanism in
exsanguination-induced bronchoconstriction (EIB) was studied in guinea pigs. We used a total of 36 guinea pigs divided into three age categories (immature, adolescent, and mature). Each age category was separated into two groups: control and
catalase (CAT). CAT is an
antioxidant. Both saline (the control group) and CAT were instilled intratracheally 30 min before
exsanguination. The animals were anesthetized, sternotomized and exsanguinated. Maximal expiratory flow (Vmax) was measured both before and 1-30 min after
exsanguination. In the control group,
exsanguination caused gradual decreases in both total lung capacity (TLC) and Vmax at 50% baseline TLC, and an increase in minimal lung volume, indicating EIB. EIB occurred faster in the immature than in the adolescent and mature guinea pigs, and it was significantly ameliorated by CAT. In 36 additional animals tested before
exsanguination, there was no age-related change in either airway
neutral endopeptidase (NEP) activity or lung tissue
substance P level. Thirty minutes after
exsanguination in the control groups, airway NEP activity decreased significantly in all age categories, while lung tissue
substance P level increased significantly only in the immature category. CAT prevented most of these NEP and
substance P changes. These data suggest that
exsanguination increases production of
oxygen radicals, which inactivate NEP and enhance breakdown of
substance P precursor; the increased
tachykinin levels induce EIB. Furthermore, our data indicate that this chain reaction is age-dependent, with a faster and more severe reaction in immature guinea pigs.