Beta-Adrenergic Blockade with Pindolol (LB-46) in Mild to Moderate Asthma

Characteristics of Study Group

Subject characteristics are shown in Table 1. All had mild to moderate asthma as shown by comparison of FEV1/FVC and the FEV1/FEV1 predicted. There were 13 male and 11 female subjects. As noted, all had at least 10 percent improvement in FEVi following inhalation of isoproterenol.

Presence of Exercise-Induced Bronchospasm

We compared postexercise with preexercise pulmonary function for the placebo trial to demonstrate the presence of exercise-induced bronchospasm. Comparisons of the mean baseline measurements with the mean of the worst postexercise FVC, FEVi, Vmax50S isovolume, FEF25-75 isovolume, PEFR, and SGaw are shown in Table 2. All were significantly reduced in the postexercise period (P < 0.05).
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Presence of Beta-Adrenergic Blockade

Evidence of beta-adrenergic blockade is shown by comparison of mean resting and maximal heart rates during cycling exercise between the placebo and pindolol trials. Means of heart rates and V02 are shown in Figure 1. The mean resting heart rates on pindolol, 76 ± 2 beats per minute (mean ±: SEM), and on placebo, 78 ±: 2 beats per minute, were not significantly different. However, mean maximal heart rates during exercise were different (P < 0.05), 145 ± 3 for pindolol and 171 ± 4 for placebo. In addition, heart rates during unloaded pedalling were also significantly different, 89 ± 2 for pindolol and 96 it 3 for placebo. Maximal V02 was slightly but significantly less on pindolol, 1.90 dr 0.09 1/min STPD, than after placebo, 1.99 ± 0.10 1/min STPD (P < 0.05).

Comparison of Postdrug and Postexercise Pulmonary Function

One subject did not complete both the placebo and pindolol trials. Following administration of one IV drug dose, the subject complained of faintness while sitting upright, and had bradycardia, hypotension, and diaphoresis. He became asymptomatic within two hours with IV fluid administration. This trial was later found to be the placebo infusion for this subject. Neither has placebo nor pindolol data are included in the postexercise results.

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We compared each pulmonary function measurement with that day’s baseline:

  • immediately after drug infusion;
  • using the smallest postexercise value in the 30 to 60 minutes after exhausting exercise;
  • following inhalation of isoproterenol.

These results are shown in Figure 2 for FEVi, Figure 3 for Vmax50* isovolume, and Figure 4 for SGaw, expressed as mean percent of the baseline value for that day, while the other tests for pindolol and placebo trials are shown in Table 3. There was no significant difference in pulmonary function either postinfusion or postexercise between pindolol and placebo trials, although significant decreases were found after exercise for both groups. Although some were followed for 60 minutes after exercise, all subjects demonstrated their maximal decline in pulmonary function within 30 minutes of completion of exercise. The only significant differences (P < 0.05) were found for the postisoproterenol FEVi (pindolol 114.8 percent ± 2.4, placebo 123.7 percent ±: 3.0) and the postisoproterenol PEFR (111 percent dz 2.9 for pindolol, 122 percent ±: 4.8 for placebo).

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Table 1—Characteristics of Study Subjects

Age 27.9 ±10 (mean±SD)
FEVi/FVC % 67 ± 11 (mean ± SD)
FEV1/pred % 82.5 ±21 (mean±SD)
Percent improvement of FEV!* 21.3 ±11 (mean ± SD, all greater than 10 percent)
Deo, percent of predicted 121 ±20

Table 2—Comparison of Postexercise Pulmonary Function for Placebo Trial

Baseline Postexercise
FVC (L) 4.38 ±0.19 3.87 ± .20 (88.0 ±2.7)
FEVi (L) 2.94 ±0.15 2.45 ±0.15 (84.9 ±4.0)
FEF25-75 isovolume (L/sec) 2.25 ±0.17 1.48 ±0.21 (81.0±7.1)
Vmax50% (L/sec) 2.59 ±0.19 1.81 ±0.23 (71.0 ±8.0)
PEFR (L/sec) 6.60 ±0.40 5.20 ±0.40 (79.2 ±4.0)
SGaw (L/sec/cm H20/L) 0.117 ±0.013 0.067 ±0.011 (56.9 ±6.0)
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Table 3—Pulmonary Function After Placebo and Pindolol, Percent Baseline

Postdrug A Postexercise Postisoproterenol A
Placebo Pin dolol Placebo Pin dolol Placebo Pindolol
FVC 97 ±1 97 ± 1 88±3 86 ±3 109 ±2 106±2
FEV! 97 ±2 95 ±2 85 ±4 78 ±4 124±3 115±2f
FEF25-75 isovolume 90±4 90±5 81 ±7 76 ±7 183 12 156 11
Vmax 50% isovolume 95 ±4 93 ±5 71 ±8 61 ±8 172 ±9 156 ±10
PEFR 98 ±2 91 ±2 79 ±4 73 ±4 122±5 111 3f
SGaw 79 ±6 92 ±6 57 ±7 58 ±6 210 21 212±30

Mean Heart Rates
Figure 1. Comparison of mean heart rates and Vo2 at rest (fl), during unloaded cycling (O), and at maximal exercise (Af) following administration of pindolol, 0.4 mg IV (closed circles) or placebo (crosses). Brackets indicate SEM.

FEV
Figure 2. Mean FEVa, as percentage of baseline, for pindolol (closed circles) and placebo (open circles) trials as measured postinfusion, as minimum value during the 30 to 60 minute period following exhausting exercise, and then after isoproterenol inhalation. Brackets indicate SEM.

Vmax
Figure 3. Mean Vmax50% isovolume, as percentage of baseline, for pindolol (closed circles) and placebo (open circles) trials as measured postinfusion, as minimum value during the 30 to 60 minute period following exhausting exercise, and then after isoproterenol inhalation. Brackets indicate SEM
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SGaw
Figure 4. Mean SGaw, as percentage of baseline, for pindolol (closed circles) and placebo (open circles) trials as measured postinfusion, as the minimum value during the 30 to 60 minute period following exhausting exercise, and then after isoproterenol inhalation. Brackets indicate SEM.