Pulmonary function of the reserpine and isoproterenol models of cystic fibrosis

Two experimental animal models exhibiting functional and morphologic changes of exocrine glands similar to those seen in patients with cystic fibrosis (CF) have been reported in the rat: chronic stimulation with reserpine (Martinez et al. 1973 Pediatr. Res. 9:463, 470) and chronic stimulation with isoprenaline (Sturgess and Reid 1973 Br. J. Exp. Pathol. 54:388). We have studied the pulmonary function of these models induced by injecting rats subcutaneously with reserpine (RES, 0.5 mg/kg/day), isoproterenol (ISO, 25 mg/kg/day), or saline (Con, 1.0 ml/kg/day) for 6 days. Plethysmographic measurements were made for functional residual capacity (FRC), airways resistance (Raw), specific airways conductance (sGaw), phase difference between air flow rate and mean alveolar pressure (PD), frequency of breathing (f), and tidal volume (VT) of the anesthetized rats. In the RES and ISO rats, the FRC, Raw and f were not different from Con values. The PD was greater and the VT was less than Con values (p less than 0.05). The results of both studies indicate uneven ventilation (increased PD) and penduluft (decreased VT) consistent with maldistribution of resistance and/or compliances of the peripheral airways and/or alveolar compartments. These physiologic effects can be related to the morphologic changes reported for the airways of rats under chronic adrenergic stimulation (ISO) and expected for rats under chronic catecholamines depletion (RES). Since peripheral airways involvement is usually the earliest pulmonary lesion found in CF, these studies indicate that the RES and ISO models may be representative of the early pulmonary involvement of CF.