To assess the reliability and within subject variability of steady-rate ventilation (VE), oxygen uptake (VO2), heart rate, systolic and diastolic blood pressure, 4 subjects exercised for 10 minutes at 3 work rates on a bicycle ergometer: 50 W, 125 W and 55% of maximum work rate (55% max). Each testing session included two work rates and only 2 testing sessions were scheduled per week. The order of the work rates was counterbalanced. In 8 to 10 weeks, 3 of the subjects completed 20 trials at 50 W while the fourth subject completed 11 trials, and all the subjects completed 10 trials at 125 W and 55% max. The within subject variability (S2w) was expressed as a percent of the mean steady-rate response. VO2 ranged from 21.2% to 27.5% of VO2max at 50 W, from 37.7% to 49.7% at 125 W and from 42.9% to 63.7% at 55% max. The S2w averaged 6.8% for VE, 4.3% for VO2, 3.2% for heart rate, 7.3% for systolic blood pressure and 10.5% for diastolic blood pressure. Reliability coefficients were calculated for the steady-rate scores by dividing the between subject variation by the total variation. The reliability was similar for VE, VO2 and heart rate and ranged from r = 0.69 to r = 0.97. Systolic and diastolic blood pressure reliabilities were lower and ranged from r = 0.27 and r = 0.80. In summary, the steady-rate ventilation, oxygen uptake and heart rate responses were reliable and consistent. The reliability of blood pressure was low. It is possible that this low reliability may result from variability in stroke volume or total peripheral resistance.

1. The pharmacokinetics of single oral doses of 20 mg lisinopril and 0.25 mg digoxin, given alone and together, have been studied in 12 normal young male volunteers. 2. Peak serum conc of lisinopril occurred at 6 to 8 h and were slightly higher during combined treatment. Subsequent elimination proceeded moderately rapidly in both cases, concn declining to approx. 25% of peak values in 24 h. The AUC of lisinopril was similarly slightly higher during combined treatment. 3. After lisinopril alone, urinary elimination of unchanged lisinopril was 13% dose in 72 h, and after combined therapy was 17% dose. 4. Although there were no statistically significant differences in lisinopril pharmacokinetics during single or combined treatment, serum and urinary parameters suggest that bioavailability may be enhanced slightly during combined treatment. 5. Plasma concentrations of digoxin were slightly lower and urinary excretion slightly higher during combined treatment, the mean renal clearance being 20% higher.

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Ketanserin is a serotonin S2-receptor antagonist that lowers blood pressure and inhibits platelet aggregation. Ketanserin treatment is also associated with prolongation of the corrected QT interval. The recently reported Prevention of Atherosclerotic Complications with Ketanserin (PACK) trial confirmed this prolongation of QT and also revealed a significant excess of deaths in patients receiving ketanserin together with potassium-losing diuretics. The investigators suggested that this excess of deaths may have been attributable to exacerbation of hypokalemia-induced ventricular arrhythmias by the repolarization-prolonging effect of ketanserin. However, drugs that prolong the QT interval may affect ventricular ectopic activity beneficially, and our study was designed to evaluate the effects of ketanserin on ventricular ectopic activity. Twenty patients (18 male, 2 female) aged 42-73 years were studied, each having at least 15 ventricular ectopic beats/hour. The study design was a double-blind, crossover comparison of ketanserin, 40 mg twice daily, and placebo, both given for 1 week. Ventricular ectopic activity was assessed by 48-hour Holter electrocardiogram (ECG) tapes at the end of each treatment period. Ketanserin treatment was associated with prolongation of repolarization, as reflected by the significant mean increases in both QT interval (+30 ms; p less than 0.001) and corrected QT interval (+20 ms; p less than 0.05). The mean overall degree of ventricular ectopic activity, as represented by a score based on the Lown classification, was significantly reduced (p less than 0.05). This was associated with a concordant improvement in the individual indices of ectopic activity. Our results show that ketanserin significantly suppressed ventricular ectopic activity in our normokalemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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