Methylprednisolone increases sensitivity to beta-adrenergic agonists within 48 hours in Basenji greyhounds.

BACKGROUND: Corticosteroids used in combination with bronchodilators are significantly more effective than placebo combined with bronchodilators in the acute treatment of bronchospasm. Because the time course for this effect is not known, and is of importance in the preoperative preparation of patients with reactive airway disease, the authors investigated the time course by which methylprednisolone increased sensitivity to the beta-adrenergic agonist, albuterol, in a dog model with airway hyperresponsiveness. METHODS: Airway responsiveness to methacholine alone and in the presence of albuterol was determined before treatment with methylprednisolone in nine Basenji greyhounds. Each dog was then treated with methylprednisolone for 1 week. Airway responsiveness to methacholine in combination with albuterol was determined after 24 h, 48 h, and 1 week of methylprednisolone treatment. RESULTS: Albuterol alone did not alter airway responsiveness to methacholine in Basenji greyhounds before methylprednisolone treatment and after 24 h of methylprednisolone treatment. Methylprednisolone, however, significantly decreased pulmonary responses to methacholine in albuterol-pretreated dogs at 48 h. CONCLUSIONS: The authors concluded that methylprednisolone increased sensitivity to the beta-adrenergic agonist, albuterol, within 48 h.

Amrinone attenuates airway constriction during halothane anesthesia.

BACKGROUND: Phosphodiesterase (PDE) inhibitors should, in theory, be useful in patients with both cardiac and reactive airway disease who require anesthesia. The effects of the PDE inhibitor, amrinone, on the release of endogenous catecholamines and on airway reactivity to aerosol methacholine challenge were evaluated during thiopental/fentanyl and halothane anesthesia in five mongrel dogs. METHODS: Responses to methacholine aerosol challenge (0.03, 0.075, 0.15, 0.30, 0.75, and 3.0 mg/ml) were measured during four conditions: thiopental/fentanyl anesthesia, thiopental/fentanyl anesthesia with amrinone infusion, halothane anesthesia, and halothane anesthesia with amrinone infusion. Increase in pulmonary resistance (RL) and decreases in dynamic compliances (Cdyn) were calculated for each methacholine dose. Plasma epinephrine and norepinephrine concentrations were measured during thiopental/fentanyl anesthesia with amrinone infusion. RESULTS: Before aerosol challenge, baseline RL and Cdyn did not differ in the four groups. Amrinone significantly attenuated the pulmonary response to methacholine during both thiopental/fentanyl and halothane anesthesia. Plasma catecholamine concentrations did not increase during amrinone infusion. CONCLUSIONS: Amrinone attenuates methacholine-induced airway responses even during halothane anesthesia. These data indicate that isozyme-selective PDE inhibitors hold promise for the perioperative treatment of bronchospasm.

Contractile responses of guinea pig trachea to oxybarbiturates and thiobarbiturates.

To determine what mechanisms are involved in barbiturate-induced tracheal constriction and whether a relationship exists between barbiturate structure and the ability of the barbiturate to induce constriction, we compared the effects of thiamylal, thiopental, methohexital, pentobarbital, and phenobarbital at increasing airway tone in an intact guinea pig tracheal preparation in the presence and absence of cyclooxygenase and thromboxane synthetase inhibition. Whole tracheas were suspended between two cannulas in 50-ml tissue baths and perfused at a constant flow rate with Krebs-Henseleit solution. The contractile responses were assessed by measuring the pressure differential between the tracheal inlet and outlet ports. Barbiturates were added to the bath of each trachea, which was washed between each drug. Each drug was added to produce final bath concentrations of 10(-6), 10(-5), 10(-4), 10(-3), and 3 x 10(-3) M. Tracheas were also pretreated with meclofenamate (10(-6) M) (a cyclooxygenase inhibitor) and UK 37,248 (10(-8) to 10(-5) M) and OKY 046 (10(-9) to 10(-6) M) (thromboxane synthetase inhibitors), and the thiamylal protocol was repeated. All data were normalized to a concentration of carbachol (2 x 10(-6) M) that has been shown to produce maximum constriction in this preparation. Thiamylal and thiopental produced constriction beginning at 10(-4) M and reached a maximum at 10(-3) M (P less than 0.0001). Methohexital, pentobarbital, and phenobarbital did not produce any significant change in airway tone. Pretreatment with meclofenamate (10(-6) M), UK 37,248 (5 x 10(-5) M), and OKY 046 (10(-6) M) prevented thiamylal-induced tracheal constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of thiopental-induced constriction of guinea pig trachea.

The authors studied the effects of thiopental on baseline airway tone in intact guinea pig tracheas using a preparation where the epithelial (inside) and serosal (outside) surfaces were isolated. Whole tracheas were excised, cannulated, and mounted in 50-ml tissue baths. The serosal and epithelial surfaces were perfused via separate circuits with Krebs-Henseleit solution. All data were expressed as a percent of constriction produced by 2 X 10(-6) M carbachol (a concentration that elicited a 90 + % of maximal constriction). Thiopental elicited a dose-dependent constriction in all 25 tracheas. Increases in tone were first seen at 10(-5) M (14.3 +/- 1.84%; mean +/- SEM) and reached a peak at 10(-3) M (29 +/- 3.16%; P less than .0001). Responses to thiopental were similar when the epithelium was removed, when thiopental was added to the inner perfusate, and when tracheas were pretreated with 10(-5) M pyrilamine. Constriction was entirely inhibited by pretreatment with indomethacin 10(-5) M. The authors conclude that thiopental, at concentrations in the clinical range, causes a reproducible dose-dependent constriction of guinea pig trachea. This effect is mediated by constrictor prostaglandins.