Mechanical alterations of airway smooth muscle in a canine asthmatic model

Abstract

To test the hypothesis that airway smooth muscle function is mechanically altered after induction of Ig[immunoglobulin]E class antibodies, dogs were sensitized (S) to a conjugate of dinitrophenol and ovalbumin (OA) in a suitable adjuvant (aluminum hydroxide) that resulted in the production of high titers of IgE anti-OA antibodies and marked increases in airflow resistances on antigenic bronchoprovocation. Controls (C) were littermates immunized with adjuvant alone. In isometric studies, the dose- and stimulus-response relationships of isolated tracheal smooth muscle (TSM) to carbachol and electrical stimulation were similar in C and S muscles. Spontaneous phasic changes in tension and a myogenic response were observed in some S muscles. The equation (P + a) (V + b) = (PO + a)b in which P is the load, PO is the maximum tetanic tension, V is the shortening velocity and a and b are the asymptotic values in unites of force and velocity, respectively, fitted successfully to force-velocity curves obtained from C and S. Force constants were unchanged in the 2 muscles; maximum shortening velocity (0.346 .+-. 0.045 (SE) muscle lengths/s for S and 0.234 .+-. 0.022 for C) and b (0.062 .+-. 0.004 (SE) for S and 0.047 .+-. 0.003 for C) were significantly different (P < 0.05). At any load TSM from S dogs shortened isotonically to a greater extent than C. Increases in the velocity and amount of shortening may represent an important mechanism contributing to the development, degree and maintenance of IgE-mediated bronchoconstriction.