Mechanism of respiratory arrest in an animal model of acute fatal bronchoconstriction

Abstract

The cause of respiratory arrest in acute asthma is not known. By its nature, respiratory arrest is difficult to study clinically. The possible causes of respiratory arrest include cardiovascular dysfunction, respiratory muscle fatigue, and central respiratory failure. We used a dog model of respiratory arrest in acute bronchoconstriction that examined the effects of hypoxemia and intrinsic loading in an attempt to establish the mechanism. Our hypothesis was that, in a setting of hypoxemia and intrinsic loading similar to human fatal asthma, respiratory arrest is caused by a central respiratory failure, more specifically, failure of the central rhythm generator. We studied 18 dogs divided into 1) an intrinsically loaded group, 2) a hypoxemic group, and 3) both a loaded and a hypoxemic group. Intrinsic loading was induced with methacholine combined with selective beta 2-blockade, and the hypoxemia was controlled by varying inspired O2 fraction. Respiratory arrest occurred only in animals with both hypoxemia and intrinsic loading. We found no evidence of hemodynamic instability or respiratory muscle fatigue. Instead, there was an abrupt cessation of ventilation while the intensity of the central neural output was maintained. Our results are consistent with a failure of the central rhythm generator as the causal agent in respiratory arrest.