As many as 80 percent of asthmatics experience nighttime or early-morning episodes, which are difficult to treat and potentially fatal. The greater-than-normal amplitude of circadian airflow variation in many asthmatics contributes heavily to the genesis of the early 'morning dip'. Beta-agonists and corticosteroids are of limited usefulness in nocturnal asthma, and slow-release theophylline drugs, while potentially effective, vary in 24-hr blood profile and hence their influence on nocturnal episodes. Traditional 12-hr 'symmetric' theophylline regimens, instead of meeting increased nocturnal demands, may actually produce lower night- than daytime blood levels. On the other hand, appropriately timed administration of a once-daily theophylline drug might provide maximum blood levels when needed and help stabilize 24-hr airflow. Accumulated data, summarized in this review, demonstrate the chronotherapeutic potential of single-daily evening doses of a controlled-release theophylline preparation (Uniphyl 400-mg tablets) in nocturnal and early morning asthma. Nighttime blood concentrations with this regimen were higher than were those with Theo-Dur tablets, B.I.D., in the same total daily doses, or with once-daily morning Uniphyl administration. In fed and fasted subjects, evening administration of Uniphyl 400-mg tablets was well tolerated and did not lead to 'dose dumping.' Clinically, this treatment demonstrated advantages over B.I.D. theophylline, over single-daily morning regimens, and over prior theophylline therapy. Advantages of the evening regimen included better early-morning airflow (without significant decline later in the day), more effective symptom control, better patient acceptance, fewer night awakenings, and the obvious convenience of once-daily dosing. In addition, lung function showed greater stability, throughout the day, with once-daily evening therapy than with traditional 12 hr dosing. Uniphyl 400-mg tablets may be administered once daily to provide maximum blood levels at the time of peak bronchoconstriction, whether at night or during the day.

No abstract

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In two groups of dogs the carotid sinuses were chronically compressed bilaterally by the application of plastic Wakerlin clamps. In the first series of three dogs, the carotid sinus nerves were sectioned and the adjacent vessel walls thoroughly cleaned. Chronic carotid sinus compression resulted in an increase in arterial systolic pressure, diastolic pressure, average arterial pressure, pulse pressure, and heart rate over a period of 422 to 485 days. In the second series of five dogs, in which the carotid sinus innervation was preserved, chronic carotid sinus compression resulted in a variable but slight change in arterial systolic pressure, a consistent increase in diastolic pressure, a variable but slight change in average arterial pressure--with only one dog showing a consistent significant increase, a consistent decrease in pulse pressure, and a variable effect on heart rate over a period of 593 to 695 days. The daily administration of 6 Gm. of sodium chloride per day to the second series of dogs resulted in no appreciable changes in pressure. However, there was a tendency for the heart rate to decrease, with three dogs showing a significant decrease. When the salt administration was stopped, the heart rates returned to values near those observed prior to salt administration. The results suggest that in the first series of dogs, with the carotid sinuses denervated chronically, there is an increase in cardiac output and a decrease in peripheral resistance. In the second series of dogs, with innervation of the sinuses intact and with chronic compression, the results suggest a decrease in cardiac output and an increase in peripheral resistance.