Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma.

Inhaled and oral over-the-counter bronchodilators are used for self-therapy by asthmatic patients. To evaluate their safety and efficacy, we compared epinephrine and theophylline combined with ephedrine with inhaled metaproterenol and the placebo. Twelve asthmatic patients were studied in a randomized, double-blind, placebo-controlled, crossover trial comparing forced expiratory volume in 1 second (FEV1) after two inhalations of epinephrine (0.2 mg/inh), 1 minute apart, followed in 15 minutes by theophylline (130 mg) with ephedrine (24 mg) versus two inhalations of metaproterenol (0.65 mg/inh), 1 minute apart, versus placebo inhaler and tablets. Onset of FEV1 greater than 15% above baseline values occurred within 15 seconds after inhalations for 100% of epinephrine-treated patients, 92% of metaproterenol-treated patients, and 33% of placebo-treated patients. FEV1 responses were significantly greater (P less than .05) for epinephrine at 0.66 to 1.66 minutes compared with the responses of metaproterenol, and epinephrine and theophylline that was combined with ephedrine compared with metaproterenol beginning at 2 hours. Mean duration of activity was 5.7 hours for the epinephrine- and theophylline with ephedrine-treated patients, 4.9 hours for metaproterenol-treated patients, and 2 hours for the placebo group. There were statistically significant differences for patients receiving epinephrine and theophylline with ephedrine versus the placebo group (P less than .001), metaproterenol patients versus the placebo group (P = .02), and patients receiving epinephrine and theophylline with ephedrine versus metaproterenol-treated patients (P less than .05). Compared with inhaled metaproterenol, inhaled epinephrine followed in 15 minutes by a theophylline-ephedrine tablet had a significantly earlier onset, longer duration of action, numerically greater peak effect, and patient preference.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravenous prostaglandins F2 alpha and E2 in hypoxic and non-hypoxic rabbits with elastase induced emphysema.

To determine whether the pulmonary and circulatory effects of intravenous Prostaglandins F2 alpha and E2 are altered in the presence of emphysema and/or hypoxia, 19 New Zealand White rabbits were treated with 3 doses of intratracheal porcine pancreatic elastase (100 U/kg) administered at 4 day intervals to induce panacinar emphysema, and 19 were treated on a similar schedule with saline to serve as controls. Thirty days after their last elastase or saline treatment, rabbits were divided randomly into hypoxic and non-hypoxic breathing subgroups, so that there were 4 experimental groups: control/non-hypoxic (n = 10), control/hypoxic (n = 9), elastase/non-hypoxic (n = 11), and elastase/hypoxic (n = 8). All rabbits underwent pulmonary physiologic studies and received rapid intravenous infusions of PGF2 alpha (6, 12, 14 micrograms) and PGE2 (1,3,6 micrograms). Lung resistance (RL), dynamic lung compliance (Cdyn), right ventricular systolic pressure (Prv), and mean aortic pressure (Paorta) were measured before, and 1 and 5 min. after prostaglandin infusions. At the conclusion of these studies, all rabbits were killed for morphometric and light microscopic analysis of their lungs. Elastase treated rabbits and physiologic, morphometric, and light microscopic evidence of panacinar emphysema. In the control/non-hypoxic group, PGF2 alpha had no effect on Cdyn, but produced a decline in Paorta and an increase in RL and Prv after the 24 micrograms dose. In the same group, PGE2 had no effect on RL or Cdyn, but a decrease in Paorta was observed with all 3 doses. In addition, Prv increased after 6 micrograms of PGE2. These effects were produced by doses of PGF2 alpha and PGE2 which were 12 and 3 times greater respectively than effects of similar magnitude in dogs. Except for the absence of an increase in RL after PGF2 alpha 24 micrograms, the presence of emphysema did not alter the effects of PGF2 alpha or PGE2. However, hypoxia irrespective of emphysema produced greater physiologic effects from both prostanoids. These findings indicate that rabbits are more resistant to the effects of PGF2 alpha and PGE2 on pulmonary mechanics, and pulmonary and systemic vascular pressures. Furthermore, they suggest that hypoxia is a more important factor influencing pulmonary prostaglandin catabolism than anatomic pulmonary emphysema.

Variability of pulmonary responsiveness to aerosolized histamine in normal rabbits.

Considerable between-subject variability in pulmonary responsiveness to histamine has been reported in normal human subjects, dogs, guinea pigs, and rhesus monkeys, but rabbits have not been studied. We determined the between- and within-rabbit variability of pulmonary histamine responsiveness in 34 anesthetized and mechanically ventilated New Zealand White rabbits. In 30 rabbits, 5 breaths of aerosolized histamine were delivered in 9 increasing concentrations ranging from 0.01 to 100 mg/ml. Eleven of 30 rabbits were rechallenged with histamine on 1-4 additional occasions over a 3-week period. In the remaining 4 rabbits, 9 doses of distilled H2O were aerosolized to determine the degree of spontaneous variability in measurements of lung resistance (RL) and dynamic lung compliance (Cdyn). We defined an increase in RL of greater than 50% of baseline (TD50RL) and a decrease in Cdyn of greater than 25% of baseline (TD25Cdyn) as being significant based on observations in these 4 rabbits. These limits exceeded the 99.9 percentile of spontaneous variability in RL and Cdyn. Pulmonary responsiveness to histamine varied widely, with a greater than 10,000-fold range in TD50RL and a 1,000-fold range in TD25Cdyn between the most and least sensitive rabbits. The variability of this responsiveness was log-normally distributed. It was not correlated with age, sex, or baseline RL and Cdyn. In contrast, within-rabbit responses to histamine challenge were quite reproducible. Five of 30 rabbits were killed at the conclusion of their histamine challenges for pathologic examination of their lungs. No evidence of airway inflammation was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intravenous and aerosolized arachidonic acid on alveolar epithelial permeability in rabbits.

To determine whether arachidonic acid (AA) alters alveolar epithelial permeability, we studied the effect of both continuous intravenous and aerosolized AA on clearance of [99m]Tc-DTPA from lung to blood in rabbits. Although intravenous AA increased prostacyclin production and aerosolized AA decreased systemic blood pressure, neither continuous intravenous nor aerosolized AA augmented alveolar epithelial permeability.