Lack of effect of a high-fat meal on the volume of distribution of theophylline in humans.

The pharmacokinetics of intravenously administered theophylline were studied in five healthy nonsmokers. Each subject received 5 mg/kg of theophylline as aminophylline after an overnight fast and again after a standard high-fat meal. Although there was wide between-day variation in the elimination rate constant in three of the five subjects, no statistically significant differences were observed in area under the time-versus-concentration curve, maximum serum theophylline concentration, elimination rate constant, or apparent volume of distribution between the two treatments. A statistical power analysis indicated that if differences in volume of distribution and maximum serum theophylline concentration occur in the general population, the mean differences are less less than 15% and 20%, respectively. This suggests that alterations in intravascular drug distribution resulting from eating a high-fat meal do not contribute importantly to previously reported effects of food on serum theophylline concentrations after oral dosing.

Red blood cell pulmonary capillary transit time during exercise in athletes.

The purpose of this study was to test the hypothesis that the exercise-induced hypoxemia observed in endurance athletes is due to a reduction in the mean red blood cell pulmonary capillary transit time consequent to a plateau in pulmonary capillary blood volume (Vc) as exercise intensity progresses from moderate to heavy levels. Measurements of Vc, mean transit time, arterial O2 tension (PaO2), and end tidal-arterial O2 tension difference (AaDO2) were made in 16 subjects (mean maximal oxygen uptake (VO2max) = 4.90 l.min-1) at rest and during five cycle exercise bouts designed to elicit 55, 65, 75, 85, and 95% VO2max. Mean PaO2 fell from 101 mm Hg at rest to 85 mm Hg during heavy exercise. Mean AaDO2 increased linearly from one stage to the next and at the highest work rate equaled 22.3 mm Hg. Mean Vc failed to plateau with increasing exercise intensity and increased on average by 16 ml from one stage to the next. Mean transit time, on average, dropped from 1.05 s at rest to 0.46 s at the lowest work rate. Mean transit time did not decrease further with increasing exercise intensity (range, 0.42-0.46 s). We conclude that, under the conditions of this study, the AaDO2 increases and PaO2 decreases observed in endurance athletes during exercise of increasing intensity is not caused by a plateau in Vc and a consequent reduction in mean transit time.

Innervation of airway smooth muscle in the baboon: evidence for a nonadrenergic inhibitory system.

The distribution of receptors and the innervation of intrapulmonary and extrapulmonary baboon airways were examined using tissue bath techniques. Acetylcholine and histamine (via H1-receptors) elicited contractions of all airways. Norepinephrine had both an excitatory (via alpha-receptors) and inhibitory (via beta-receptors) effect in trachealis strips, but in intrapulmonary airways, only inhibitions were observed. Transmural electrical stimulation of resting airways produced sustained contractions that were blocked by either 5 x 10(-6) M tetrodotoxin or 10(-6) M atropine. Electrical stimulation also caused relaxations of histamine-induced contractions in airways pretreated with 10(-6) M atropine and 10(-6) M phentolamine. Relaxations were blocked by 10 x 10(-6) M tetrodotoxin but were unaffected by either 10(-6) M propranolol or 10(-5) M guanethidine. The response of airways to exogenous ATP depended on the degree of active tone. ATP caused contractions in resting airways and airways with moderate tone. In contrast, ATP relaxed airways with high active tone. We conclude that a nonadrenergic system constitute the primary inhibitory innervation of baboon airways, but whether ATP might act as the neurotransmitter could not be determined.

Evidence for alpha-adrenergic innervation of the isolated canine thoracic duct.

The excitatory innervation of isolated thoracic duct segments was studied using tissue bath techniques. No spontaneous activity was present in longitudinal or helical strips obtained from a portion of the thoracic duct cephalad to the hilum of the lung. Norepinephrine (10(-8) to 10(-5) M) and tyramine (3 x 10(-5) M) produced contractions that were antagonized by phentolamine (2 x 10(-5) M) and phenoxybenzamine (10(-7) M). Acetylcholine (10(-7) to 10(-4) M) produced contractions that were antagonized by atropine (5 x 10(-9) M). Thoracic duct strips also contracted in response to field electrical stimulation, and maximal responses were obtained with a stimulus of 15 V, 15 Hz, and 1-ms pulse duration. These electrically induced contractions were abolished by tetrodotoxin (5 x 10(-7) M), phentolamine (2 x 10(-5) M), phenoxybenzamine (10(-7) M), and guanethidine (3 x 10(-6) M), but not by atropine (10(-6) M). We conclude that smooth muscle of the canine thoracic duct contains alpha-adrenergic and acetylcholine receptors, both of which cause contraction when stimulated. However, only the alpha-receptors appear to be innervated.