Bronchodilating effects of the anesthetic ketamine in an in vitro guinea pig preparation

Ketamine, a dissociative anesthetic, is capable of reducing airway resistance and has proved useful in anesthetizing surgical patients with acute or chronic bronchospasm. To determine if ketamine alters smooth muscle tone, the relative responses of large and small airways of the same animal were studied by comparing the pharmacologic reactivity of tracheal smooth muscle strips with that of a specially prepared perfused bronchial tree. Trachealis and bronchial smooth muscle were found to react to methacholine and histamine in a concentration-dependent manner and have similar sensitivities. Ketamine, by itself, in the concentration range 10^-8-10^-3 M did not alter resting tone as compared to epinephrine, which reduced baseline tone. In tissues precontracted with histamine or methacholine at ED₅₀ doses, ketamine inhibited smooth muscle contraction. In a second series of experiments, the dose-dependent contraction of smooth muscle to histamine and methacholine was reevaluated in the presence of ketamine. Both tissue sensitivity and maximum contractile response to these agonists were reduced by ketamine at 10^-4 M. These data indicate that ketamine alters the in vitro response of guinea pig airways to agonists associated with the asthmatic state. Although ketamine does not reduce airway tone in nonstimulated tissues, its effects on agonist-induced contraction of airway tissues in vitro are consistent with clinical observations that ketamine relieves bronchospasm.