ANAPHYLACTIC BRONCHOCONSTRICTION IN IMMUNIZED GUINEA-PIGS PROVOKED BYINHALATION AND INTRAVENOUS ADMINISTRATION OF HEXAHYDROPHTHALIC ANHYDRIDE AND METHYLTETRAHYDROPHTHALIC ANHYDRIDE

We established a guinea-pig model of anaphylactic bronchoconstriction provoked in immunized animals by inhalation and intravenous administra tion of 4,4-methyltetrahydrophthalic anhydride (MTHPA) and hexahydroph thalic anhydride (HHPA). Guinea pigs were immunized intradermally with either MTHPA (n = 8) or HHPA (n = 8) suspended in olive oil. Control animals (n = 8) were injected with olive oil alone. After 4 weeks, the animals were challenged during mechanical ventilation by inhalation o r intravenous administration of MTHPA or HHPA conjugated with guinea-p ig serum albumin (GPSA). Airway now, and airway and esophageal pressur es were measured. Resistance (R) and static compliance (Cst) of the re spiratory system (rs), lung (1), and chest wall were studied with the flow-interruption technique. After challenge with MTHPA-GPSA or HHPA-G PSA, R,rs and R,1 increased dramatically while Cst,rs and Cst,1 decrea sed, and severe arterial hypoxia developed. The reaction occurred at a well-defined dose of anhydride and lasted about 30 min. When the same dose was repeated after 30 min, the response was much attenuated. MTH PA and HHPA can induce asthma in guinea pigs. The dose-response curve at antigen challenge is steep. Once a threshold dose is reached, a sev ere reaction occurs. The reactivity is then exhausted. This model may be suitable for assessing occupational asthma caused by acid anhydride s and possibly by other low-molecular-weight chemicals.