Middle ear mucosal inflammation: an in vivo model.
The inflammatory process underlies the pathogenesis of otitis media (OM). Although knowledge concerning this common childhood disease continues to accumulate, most of the basic science research is based on in vitro or ex vivo methodologies. Magnetic resonance imaging (MRI), although lauded for its ability to image soft tissue, is often neglected as a research tool providing real-time in vivo information. This study attempts to assess experimental middle ear (ME) inflammation using MRI. The vasoactive effects of histamine and its interaction with antihistamines and a glucocorticoid were evaluated. Histamine was chosen because it is one of the naturally occurring inflammatory mediators. The antagonists were selected on the basis of their antihistaminic and vasoactive effects, respectively. Certainly there is substantial clinical interest in these agents because their efficacy for the treatment of OM is still being debated. The chinchilla model was chosen since it is one of the best characterized species in the study of OM. The three parts of the study are as follows: the effects of histamine on chinchilla ME mucosa; histamine challenge following pretreatment using hydroxyzine hydrochloride (H1 antagonist), ranitidine chloride (H2 antagonist), and the combination; and histamine challenge following pretreatment with dexamethasone. Sequential T1-weighted spin-echo (SE) MRI was used to detect extravasation of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) into the middle ear effusion (MEE). The results indicate that the vasoactive effects of histamine are dose-related and can be assessed across a wide spectrum of histamine dosages inclusive of the human MEE levels. The H1 antagonist alone, or in combination with the H2 antagonist, was able to prevent the increased vascular permeability induced by histamine. When used alone, the H2 antagonist did not abolish the effects of histamine. The vasoactive effects of histamine were also ameliorated by pretreatment with a glucocorticoid. These findings indicate the utility of MRI for assessing mucosal inflammation in a real-time manner rather than as an accumulation of events. This study also validates the efficacy of an H1 antagonist and a glucocorticoid in counteracting the vasoactive effects of histamine. This methodology may be suited for evaluating the effects of other classes of antiinflammatory mediators.
Chan
K H
KH
Dept. of Otolaryngology, University of Colorado Health Science Center, Children's Hospital, Denver 80218.
Swarts
J D
JD
Tan
L
L
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002682:Chinchilla; D003287:Contrast Media; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004432:Ear, Middle / Q000187:drug effects / Q000473:pathology; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000473:pathology / Q000503:physiopathology; D005682:Gadolinium; D019786:Gadolinium DTPA; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation; D008279:Magnetic Resonance Imaging; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D009942:Organometallic Compounds; D010033:Otitis Media / Q000473:pathology* / Q000503:physiopathology; D004369:Pentetic Acid / Q000031:analogs & derivatives; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects
D003287:Contrast Media; D009942:Organometallic Compounds; D014662:Vasoconstrictor Agents; D006919:Hydroxyzine; D004369:Pentetic Acid; D003907:Dexamethasone; D006632:Histamine; D011899:Ranitidine; D005682:Gadolinium; D019786:Gadolinium DTPA