The effect of bronchial blood flow on hyperpnea-induced airway obstruction and injury.

Abstract

IntroductionWe examined the effect of bronchial blood flow (BBF) on hyperpnea-induced airway obstruction (HIAO) in dogs. HIAO in in situ isolated pulmonary lobes with or without BBF was monitored via a bronchoscope. An intravascular tracer in conjunction with morphometric analysis was used to document the efficacy of our occlusion technique. We found that (a) Occlusion of the bronchial artery abolished bronchovascular leakage, but did not alter HIAO; (b) HIAO occurred in postmortem dogs, and was attenuated by cooling; (c) absence of BBF did not cause mucosal damage, although hyperpnea-induced injury was enhanced in airways lacking BBF; (d) BBF did not affect either goblet/ ciliated cell ratios or hyperpnea-induced goblet cell degranulation; (e) ligation of the bronchial artery and hyperpnea each caused mast cell degranulation, and these effects were additive; (f) hyperpnea-induced leukocyte infiltration was reduced in the absence of BBF; and (g) ligation of the bronchial artery and hyperpnea with dry air each increased airway vessel diameter, and these effects were additive. We conclude that either impairment or absence of BBF abolishes bronchovascular leakage and increases hyperpnea-induced mucosal injury, but fails to affect HIAO. Based on these results we speculate that bronchovascular leakage protects the bronchial mucosa from excessive losses of heat and water, and inhibits mucosal damage. (J. Clin. Invest. 1995.

Hyperventilation-induced airway injury and vascular leakage in dogs: effects of α1-adrenergic agonists

“…1, Table 1). Unlike in previous studies that used 5-min rather than 2-min exposure times (13,14,26,27), DAC in the present study did not cause G/C (an indicator of goblet cell degranulation and mucosal perturbation) to decrease (Fig. 2).…”

Eicosanoid and muscarinic receptor blockade abolishes hyperventilation-induced bronchoconstriction

“…Positive correlations between PGF 2␣ , TxB 2 , and BALF epithelial cells (Fig. 4) probably reflect injuryinduced mediator production and release from either epithelial cells or mucosal mast cells (15,38), and are consistent with the notion that mucosal cells are local sources for these prostanoids. Although other potential sources include macrophages, neutrophils, and eosinophils (13), no positive correlations were detected between any prostanoid and any leukocyte recovered in BALF (all P Ͼ 0.31).…”

“…This conjecture has been confirmed in dogs by using morphometric analysis (16,37). In addition to damaging bronchial epithelia, hyperventilation with cool dry air stimulates mast cell degranulation in dogs (15,38) and human asthmatic subjects (6,35). The fact that bronchial epithelial cells and mast cells can secrete a wide variety of proinflammatory eicosanoids (4,35,40,59) is consistent with the hypothesis that the bronchial mucosa plays an important modulatory role in the development of HIB.…”

“…However, just as neurokinins can stimulate leukotriene and prostanoid release in the lung (3,32,33), leukotrienes and prostanoids can stimulate neuropeptide release (21,54). Thus it is possible that hyperventilation-induced mast cell degranulation (15,38) results in eicosanoid-induced release of neuropeptides from sensory nerve fibers, resulting in bronchoconstriction. This scenario is consistent with our observation that treatment with MK-Indo (Fig.…”

Models and mechanisms of exercise-induced asthma

“…In addition, although eicosanoid and tachykinin antagonists in guinea-pigs and β 2 -receptor agonists in dogs significantly attenuate AIB (table 1), they do not alter hyperpnoea-induced vascular leakage in these species [67,69,179]. Finally, ligation of the bronchial artery during hyperpnoea abolishes bronchovascular leakage and increases mucosal injury, but fails to affect hyperpnoea-induced airway obstruction in dogs [65]. This finding represents the first direct demonstration that blood flow within the bronchial circulation does not determine the magnitude of AIB.…”