Age-dependent mechanism in guinea pig bronchoconstriction induced by exsanguination

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.