Relationship among Mediators, Inflammation, and Volume History with Antigen versus Hyperpnea Challenge in Guinea Pigs

Abstract

Paralyzed mechanically ventilated guinea pigs constricted to a similar degree by either isocapnic hyperpnea or antigen challenge display significantly different lung resistance (RL) volume history responses to a deep breath. We compared bronchoalveolar lavage (BAL) mediator profiles, BAL total protein concentrations, and tissue histopathology of antigen-constricted (AC), hyperpnea-constricted (HC), and control guinea pigs to determine whether patterns of volume history near peak constriction could be related to specific patterns of lung mediators, indices of microvascular leakage, or severity of tissue inflammation assessed pathologically. Methacholine constricted (MC) animals served as a second control group for assessing the effects of direct smooth-muscle contraction on indices of inflammation and volume history responses. Our results show that despite similar baseline and postchallenge RL, HC and MC animals displayed significant constriction reversal after a deep lung inflation, whereas AC animals did not. BAL concentrations of prostaglandin D2(PGD2), thromboxane B2 (TxB2), and leukotriene C4/D4/E4 (slow reacting substance of anaphylaxis, SRSA) were significantly elevated in both AC and HC animals compared with control and MC animals, with AC and HC BAL differing only with respect to PGD2 values (AC 2.4-fold higher). BAL total protein in AC animals was significantly greater than in HC, MC, and control animals. Histopathology showed significant peribronchial and interstitial cellular inflammation in AC animal specimens, whereas specimens from HC animals had little or no inflammation. Differences in volume history responses observed between equally constricted AC, HC, and MC animals may be due to differences in airway and/or parenchymal microvascular leak and cellular inflammation.