The effect of a single prophylactic dose of
tin protoporphyrin on the
carbon monoxide (CO) excretion rate of
antibiotic-treated neonatal rats before and after
hematoma formation was evaluated. The CO excretion rate, reflecting the rate of
bilirubin production, of
tin protoporphyrin-treated (TP-H) rats 24 hours after injection of 65 mole of
tin protoporphyrin per kilogram (time [t] = 0 hours) was approximately 18% lower than those of the saline-control (S-C) and saline-
hematoma (S-H) rats, but this difference was no longer evident at t = 43 hours. After
hematoma formation at
t = 44 hours, the CO excretion rate of the S-H rats increased rapidly; this increase was delayed and lessened in the TP-H rats. At eight hours posthematoma (t = 52 hours), the CO excretion rate of the TP-H rats was significantly lower than that of the S-H rats, 53 +/- 2 vs 73 +/- 3 microL/kg/hr, respectively. A maximal rate of 89 +/- 5 microL/kg/hr was reached 25 hours posthematoma in the S-H rats (t = 69 hours), as compared with 80 +/- 3 microL/kg/hr at 44 hours posthematoma in the TP-H rats (t = 88 hours). The recovery of injected blood as CO over a 68-hour study period was approximately 90% for the S-H rats and approximately 65% for the TP-H rats. At t = 112 hours, hepatic
heme oxygenase activity of the TP-H rats was still significantly lower than that of the S-H and S-C rats; however, plasma
bilirubin concentrations of all three groups were similar. These studies demonstrate that
tin protoporphyrin is an effective in vivo inhibitor of endogenous
heme catabolism as measured by the CO excretion rate in
antibiotic-treated neonatal rats with and without artificially created
hematomas.