Methohexital produces bronchod1lation in a non-stimulated guinea pig lung preparation

Pentothal, a thiobarbiturate causes histamine release from mast cells i Anesthesiology, 63: 353, 1985). We have previously demonstrated that pentothal and pentobarbital, an oxybarbiturate, inhibit bnmchoconstriction. We have now evaluated methohexital (Mhex), a methylated-oxybarbiturate, to determine if differences in the chemical structure affect their activity on the bronchial smooth muscle tone. Lungs were excised and the bronchus of the lung lobes was cannulated at the center of several lobules. Scarifications were made on the pleural surface to allow porfusate to exit through several small bronchi which were perfused with Krebs-Ringers solution at a constant flow. Perfusion pressure served as a gauge of airway resistance. Infusion of Mhex in non-constricted tissues m=6' showed a dose-dependent bronchodilation (perfusion pressures less than control baseline). Mhex concentrations of 0.2, 0.4 and 0.8 mg/ml corresponded to decreases in perfusion pressure of 2.0 ±0.4 (mean ±SEM) (p<0.007), 3.8 ±0.4 (p<0.0002> and 5.2 ±1.0 mmHg (p<O.OQ4), respectively. When Mhex was administered at lower concentrations, bronchodilation was also observed. At 0.02, 0.04, 0.08 mg/ml values below baseline were 1.3 ± 0 s mmHg (N.S.), 2.3 i 0.7 (p < .0V) and 3.3 ±1.0 (p < .02), respectively. Mhex in = 51 at 0.002. 0.004, and 0.008 mg/ml, yielded no change in pressure at 0.002 mg/ml, and non-significant bronchodilation (1.2 ±1.0 mmHg and 1.4 ±1.8), respectively at the other concentrations. In summary, barbiturate structure does not seem to be related to the effects on bronchial smooth muscle tone. The mechanism(s) have not yet been elucidated.