Forty-one patients were studied in a randomized double-blind placebo-controlled crossover trial to compare the antianginal actions of nicardipine 30 mg thrice daily and nifedipine 10 mg thrice daily. Efficacy was assessed using objective criteria from computer-assisted multistage graded exercise testing, performed after a two-week placebo run-in period and at the end of each four-week active treatment period. Thirty-seven patients completed both legs of the crossover trial. The mean (+/- standard error of the mean) baseline exercise time to development of angina was 6.7 +/- 0.4 min and this increased to 9.5 +/- 0.6 min on nicardipine (p less than 0.001) and 9.5 +/- 0.5 min on nifedipine (p less than 0.001 vs baseline; NS vs nicardipine). Both drugs significantly prolonged the time to the development of 1mm ST segment depression. The baseline resting heart rate of 83 +/- 2 beats/min increased to 87 +/- 3 beats/min during nicardipine (p less than 0.05) and remained unaltered at 83 +/- 2 beats/min during nifedipine therapy (p = NS vs baseline and p less than 0.02 vs nicardipine). Similarly, both drugs increased significantly the maximal heart rate at peak exercise. One patient was lost to follow-up during the placebo run-in period and four patients (two each on nicardipine and nifedipine) were withdrawn due to adverse effects. Our results indicate that nicardipine is comparable in efficacy to nifedipine and has a similar adverse effect profile and can also be considered a useful therapeutic agent for the treatment of chronic stable angina pectoris.

The efficacy and side effects of oxitropium bromide, a new anticholinergic bronchodilator drug, were tested in a double-blind placebo-control study. Twenty-four men, aged 58 to 72 years, with chronic partially reversible obstruction of the airways were used as subjects. Three doses of oxitropium were tested (100 micrograms, 200 micrograms, and 300 micrograms) to determine the optimum dose by metered-dose inhaler. A comparison was also made between oxitropium, fenoterol (400 micrograms), and a combination of oxitropium (200 micrograms) and fenoterol (400 micrograms). Fenoterol produced a greater degree of maximal bronchodilatation than each of the three doses of oxitropium, and its effect was more rapid in onset (30 vs 120 minutes to peak effect); however, the duration of action of oxitropium was greater than that of fenoterol (ie, the forced expiratory volume in one second [FEV1] remained within 5 percent of peak FEV1 for three hours, compared to one hour). Oxitropium in the 100 micrograms dose was inferior to 200 micrograms and 300 micrograms in subjective efficacy scores, peak percent change in FEV1, forced vital capacity, (FVC), mean forced expiratory flow over the middle half of the FVC, and duration of action; there was no difference between 200 micrograms and 300 micrograms. The oxitropium-fenoterol combination had a rapid onset of action, and a greater peak effect was achieved than for oxitropium alone. The main unwanted effect was a mildly unpleasant taste. Anticholinergic effects were not seen in this group of elderly men. Oxitropium bromide therefore is an effective bronchodilator with slow onset but prolonged activity and few side effects when used in patients with moderately severe obstruction of the airways. An appropriate dose appears to be 200 micrograms. Addition of oxitropium to fenoterol appears to offer even greater efficacy.

To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The 201Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of 201Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed 201Tl images causes increased 201Tl myocardial clearance rates and may alter 201Tl myocardial redistribution over time.

To evaluate comparative bronchodilator efficacy with chronic airflow obstruction (CAO), we randomly administered to ten patients week-long treatments consisting of: inhaled metaproterenol from a metered dose canister (1.30 mg six times a day) and doses of a sustained-release theophylline formulation sufficient to achieve plasma levels of 10-15 micrograms/ml; metaproterenol-placebo; theophylline-placebo; or placebo-placebo. At the end of each period, treatment responses were evaluated by spirometric tests, by exercise tolerance (12 minute walk and progressive cycle ergometry) and by subjective perception of dyspnea (oxygen cost diagram and breathlessness rating). Metaproterenol as a single treatment caused statistically significant improvements in spirometric variables and in the breathlessness rating. Theophylline as a single treatment caused significant changes in none of the test variables, though favorable trends were observed. Combined drug therapy was significantly better than metaproterenol only in the case of the breathlessness rating. We conclude that in the treatment of patients with CAO, inhaled metaproterenol is superior to oral theophylline. Our results permit no definite conclusion concerning added benefits of combined drug therapy.

Almitrine, a new triazine derivative, was studied in a double-blind, randomized, parallel study in 16 patients with hypoxic chronic airflow obstruction (eight almitrine and eight placebo). At rest, compared to placebo, a 3 mg/kg single dose of almitrine given orally significantly increased the partial pressure of oxygen (mean increase: +12.0 +/- SEM 2.1 mm Hg, p less than 0.001) and decreased the partial pressure of carbon dioxide (mean decrease: -6.0 +/- 0.7 mm Hg, p less than 0.001); this improvement in arterial blood gases persisted on exercise. The lack of significant change in ventilation and the decrease in the alveolar-arterial oxygen gradient (mean decrease -10.0 +/- 1.9 mm Hg; p less than 0.001) at rest suggests a change in the distribution of the ventilation-perfusion ratio in the lung; such a change was confirmed by a krypton 81m isotopic study. Pulmonary hemodynamic responses were studied at rest and on exercise; a significant but slight increase in mean pulmonary artery pressure at rest (+4.0 +/- 1.5 mm Hg, p less than 0.05) was found.

Twenty asthmatic patients clinically free of heart disease were studied for the possible arrhythmogenic action of albuterol (salbutamol). Two puffs of either albuterol or placebo were inhaled four times per day on two consecutive days and continuous ECG recordings obtained during each 24-hour period. Sixteen patients had atrial extrasystoles, four with albuterol, one with placebo, and 11 with both drugs. The extrasystoles/hour were 6.55 (23.75 SD) with albuterol and 8.37 (33.82) with placebo, a nonsignificant difference. Ventricular extrasystoles were shown in 11 patients, two with albuterol, two with placebo, and seven during both treatments. The extrasystoles/hour were 2.57 (6.36) and 3.10 (7.61) with albuterol and placebo, respectively. This difference was not significant. These findings suggest that therapeutic doses of albuterol aerosol in asthmatic patients without evidence of heart disease and severe hypoxemia should not be considered a cause of cardiac arrhythmias.

The purpose of this study was to evaluate the effects of inhaled atropine sulfate on the exercise capacity and cardiopulmonary responses to exercise in patients with chronic airflow obstruction (CAO). Eighteen patients underwent duplicate incremental (15 watts/min) maximal cycle ergometer exercise tests 60 minutes after either inhaled atropine (0.075 mg/kg) or placebo, in double blind randomized fashion on consecutive days. Bronchodilator medications were withheld before each study. Spirograms were obtained before and 60 minutes after each aerosol treatment. Atropine increased the FEV1 by 25 percent, from 1.37 +/- 0.49 to 1.71 +/- 0.52 L (p less than 0.001), as compared to placebo. Although the ventilation at exhaustion (VEmax) increased significantly (from 52.3 +/- 11.5 to 55.9 +/- 10.0 L/min, P less than 0.05) after atropine, the increase in the mean maximum work load (95 +/- 28 vs 101 +/- 19 watts) did not achieve significance. The drug resulted in a significant decrease in oxygen consumption at all equivalent workloads greater than "0" watts (unloaded cycling), presumably because the improvement in airway mechanics decreased the oxygen cost of ventilation. Atropine-induced increases in FEV1 did not result in a significant group mean increase in maximum exercise capacity, but the drug did result in a lower oxygen cost of performing work in patients with CAO.

A prospective study of 104 patients was undertaken to determine the frequency of severe heparin-induced thrombocytopenia in patients receiving either bovine lung or porcine mucosal heparin. One of 54 patients randomized to receive bovine heparin and two of 50 patients randomized to receive porcine heparin developed heparin-induced thrombocytopenia (platelet count less than 100,000/microliters). Although three previous studies suggest a remarkably high frequency of bovine heparin-induced thrombocytopenia, or a high frequency compared to porcine heparin, our study supports other evidence that clinically important, severe heparin-induced thrombocytopenia (platelet count less than 100,000/microliters) occurs in 10 percent of patients or less receiving heparin, and that there is no significant difference of occurrence between bovine and porcine heparin.

Previous studies have shown that labetalol, a new alpha- and beta-adrenergic antagonist, is relatively safe for the treatment of hypertension in patients with chronic obstructive pulmonary disease (COPD). This multicenter study was designed to evaluate its effects in hypertensive patients with asthma and propranolol sensitivity. Hypertension was successfully controlled in 18 of 21 patients who received labetalol in increasing doses, up to 1,200 mg/day. The decrease in mean FEV1 (1.5 percent) two hours after the highest dose of labetalol was not statistically significant, although there was a gradual decline in mean baseline FEV1 during the four-week treatment period. Antihypertensive agents other than adrenergic antagonists should be considered for the management of hypertension in patients with asthma, especially those with marked reversibility of airflow. If treatment with beta-adrenergic antagonists is indicated, labetalol is recommended over other currently available agents.

Many patients with irreversible chronic obstructive pulmonary disease (COPD) claim symptomatic improvement with steroid therapy, despite a lack of objective improvement in their spirometric data. To determine if steroids actually increase the exercise capacity of these individuals, 13 clinically stable patients (mean age, 63 +/- 4 years; 12 male patients) were given methylprednisolone (32 mg once daily) or placebo in a randomized double-blind crossover fashion. Spirometric data and minute ventilation, oxygen consumption (VO2), carbon dioxide production, and heart rate during incremental exercise were measured at each visit. Methylprednisolone did not produce a significant change in any of the measured parameters. Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone, while two experienced a decline in maximal VO2 of similar magnitude. The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients (r = 0.08). We conclude that in the absence of any improvement in the usual tests of airway mechanics, steroid therapy does not improve exercise performance in patients with COPD.

In unilateral parenchymal pulmonary disease, arterial oxygenation decreases when the patient is positioned such that the abnormal lung is dependent; however, few studies have evaluated the effect of the body position on oxygenation in patients with unilateral or asymmetric pleural effusions. To our knowledge, no previous study has evaluated the possible transient effects of changing position on the level of arterial oxygen saturation (SaO2) in such patients. Accordingly, we studied ten normoxic patients spontaneously breathing room air, who had asymmetric pleural effusions as documented by chest x-ray film and physical examination. We monitored pulse, respiratory rate, and blood pressure every five minutes and SaO2 by ear oximetry continuously while patients were in the following positions: sitting; supine; and left and right lateral decubitus. The mean SaO2 was 95 percent and 94.3 percent in the sitting and supine positions, respectively. Mean SaO2 fell to 93.4 percent when the patients were positioned so that the side with the largest pleural effusion was dependent. When the side with the pleural effusion was down, the mean SaO2 was significantly lower than in either the sitting position or with the side with the pleural effusion up. We could find no significant relationship between the size of the pleural effusion and the amount of arterial oxygen desaturation. We conclude that there is a decrease in SaO2 in normoxic patients when the side with the larger pleural effusion is dependent; however, this decreased SaO2 does not appear to be clinically significant in patients with normal SaO2.

Long-term ambulatory Holter-monitoring was used to evaluate the arrhythmogenic effects of beta 2-agonist therapy, alone and in combination with a xanthine derivative, theophylline or enprofylline. Twenty patients (mean age 51 years) with mild-to-moderate obstructive lung disease (bronchial asthma or chronic bronchitis), but without concomitant ischemic heart disease were studied. Compared with beta 2-agonist therapy alone, both combined regimens were associated with a small but significant increase in the frequency of ventricular arrhythmias. Few serious arrhythmias were observed, however, and the clinical significance of these findings is thought to be minor. Although adenosine has been suggested to have an antiarrhythmic effect, a difference between theophylline and enprofylline in the effect on adenosine (theophylline but not enprofylline being an adenosine antagonist) would appear to be of less cardiac relevance in patients without ischemic heart disease.

Twenty-six patients undergoing coronary bypass graft surgery were randomized in two groups. In group 1, 14 patients were subjected to inspiratory pressure support during spontaneous ventilation (IPSSV) and 12 patients in group 2 were treated with conventional ventilation (CV). The outcome of IPSSV was a definite advantage over the conventional ventilation. The patients in IPSSV group needed +/- 3 h of pressure support before tracheal extubation. The other patients in CV group 2 needed +/- 6 h of mechanical ventilation before being weaned off the ventilator.

The present study investigated the effects of oxygen therapy upon human information processing for hypoxemic COPD patients. Each of ten patients was admitted to a general clinical research center for a two-day period. In a randomly counter-balanced factorial design, patients breathed either room air or enriched oxygen for either six hours or 20 minutes prior to testing. The tests evaluated speed of information processing, ability to detect correct sequence of tones, and serial memory. In addition, patients were evaluated on critical flicker fusion and story recall. The results suggested that acute oxygen therapy does not reverse information processing deficits observed in hypoxemic COPD patients.

The effect of theophylline on the penetration of an inhaled radioaerosol in the lung, bronchial clearance, and tracheal mucociliary transport rate (TMTR) was investigated in 13 healthy volunteers. Following a randomized, double-blind, crossover protocol, subjects ingested 4 mg/kg twice daily of theophylline or placebo for three days which resulted in stable, low therapeutic serum levels. Aerosol penetration, assessed by the skew of the initial distribution of lung radioactivity, was more peripheral (p less than 0.025) with theophylline, indicating bronchodilation that was not detectable by standard pulmonary function tests. The TMTR increased in ten of 13 subjects after theophylline, but not to a significant level. Bronchial clearance was not significantly different with theophylline despite the longer clearance pathway created by the increased peripheral aerosol deposition. This finding suggests that mucus transport rates in the intrapulmonary airways were increased by theophylline.

Eighteen asymptomatic postmenopausal women volunteered to ingest 2 ml of 100-proof vodka per kg of body weight in orange juice on one night and a placebo on another. Overnight sleep monitoring was performed immediately thereafter. Alcohol ingestion caused reduction in total sleep time from 329 to 281 minutes and a decrease in rapid eye movement sleep. There was no difference from placebo in the number of episodes of apnea or hypopnea, or in the frequency, length, or severity of oxygen desaturation. In contrast to the effects of alcohol ingestion in men, the effects on breathing and oxygenation are minimal during the sleep of women if this amount of alcohol is ingested.