A CO2 rebreathing method for the measurement of cardiac output was evaluated by comparison with the direct Fick O2 method in 26 studies performed in 18 patients who were critically ill. The method requires measurement of CO2 output by collection of expired gas, of arterial PCO2, and of mixed venous PCO2 by rebreathing. Twenty-five comparisons were within +/- 20% of the direct Fick measurements, at cardiac outputs varying between 1.4 and 6.4 L/min. Knowledge of the cardiac output increased the quality of the interpretation of arterial blood PO2 measurements in the assessment of pulmonary gas exchange disturbances.

We studied the frequency of cardiac arrhythmias during routine tests of pulmonary function by using continuous electrocardiographic recording and a computerized method to quantitate arrhythmias. A total of 150 patients with chronic obstruction of airways were studied before, during, and after routine tests of pulmonary function performed before and after intermittent positive-pressure breathing (IPPB) with a bronchodilator aerosol. The only significant (P less than 0.01) change was an increased frequency of atrial premature beats during tests of pulmonary function. Spirometric studies, maximal voluntary ventilation, and IPPB with a bronchodilator aerosol were equally likely to induce atrial premature beats. Routine tests of pulmonary function represent an additional causal factor in producing arrhythmias in patients with obstruction of airways, although no clinical consequences were evident in the course of the study.

Based on a study indicating a significant rate of reactivation of tuberculosis in Veterans Administration patients with inactive disease, a cooperative study was initiated to determine the prophylactic effect of isoniazid on the rate of reactivation. A randomized double-blind study was designed, utilizing three regimens, two with isoniazid and one with placebo only. Two consecutive years of taking pills in one of the three regimens was followed by five years of observation. A total of 7,036 patients with inactive disease, some of whom had received prior chemotherapy, were entered into the study. Only 63 reactivations of tuberculosis were found, for a total rate of reactivation of 9/1,000 (less than 1%) over the seven-year period. Although no significant differences in the rate of reactivation were found among any of the regimens, there was a significant reduction in the rate of reactivation among those who had not received any prior chemotherapy and received isoniazid (INH) in this study, compared with those who received placebo only.

This study investigated the effects of continuous therapy with oxygen on the neuropsychologic functioning of aged subjects professing problems with their memory. Nineteen men (mean age, 71 years) were evaluated on eight neuropsychologic measures during three different periods of time. Subjects were tested before any treatment, after a month of continuous therapy with oxygen, and after a period of sham treatment. The results indicated statistically significant improvement in the Wechsler Memory Quotient and, with one exception, improvement in all other measurements in favor of the treatment with oxygen. Differences between the results of this investigation and those of other studies are discussed, along with the factors possibly accounting for these differences.

Bronchodilatory and side effects of fenoterol hydrobromide (Th1165a; hydroxyphenylorciprenaline; Berotec) and isoproterenol given by inhalation were compared in a double-blind crossover study involving 20 volunteer subjects with reversible obstructive disease of the airways. Subjects inhaled medications from aerosol canisters containing fenoterol hydrobromide (0.1 mg, 0.2 mg, or 0.4 mg) or isoproterenol (0.15 mg) or an inert placebo propellant in a random sequence of five testing days. All active drugs substantially increased the forced expiratory volume in one second, the mean forced expiratory flow during the middle half of the forced vital capacity, and the specific conductance. The onset of bronchodilation after both fenoterol and isoproterenol was rapid, but the effect from fenoterol lasted much longer, up to eight hours. None of the medications cuased significant tachycardia or hypertension. After inhalation of 0.1 mg of fenoterol hydrobromide, none of the subjects reported nervousness, headache, tremor, or nausea, incontrast with results reported for isoproterenol, higher aerosol doses fo fenoterol, or oral administration of fenoterol. No additional therapeutic benefit was found in the administration of higher doses of fenoterol.

Aerosolized fenoterol in a dosage of 400 microgram was compared to isoproterenol 150 microgram in 31 asthmatic subjects during the course of a double-blind parallel 90-day study. Bronchodilator activities of the two drugs were evaluated for up to 6 hours on days 1, 45 and 90. Analysis of the data revealed that fenoterol consistently produced a significantly greater increase in FEV1, FEF25-75% and Gaw/VL. Specific airway conductance increased on each test day 25 percent or more above baseline for over three hours after use of fenoterol and for only one hour after use of isoproterenol. Fenoterol has less effect upon the cardiovascular and central nervous systems, but produced a greater incidence of shaking compared to isoproterenol. Patients used fenoterol less frequently than isoproterenol which can be attributed to the former having a greater peak effect and time course of bronchodilation. The therapeutic efficacy of fenoterol was sustained throughout this three-month study, and suggests that this relatively selective beta2 adrenergic drug will provide a well tolerated, alternative aerosol for chronic use in asthma.

We have compared bronchodilator responses to atropine and terbutaline in 39 chronic bronchitics and 16 stable asthmatics. Fasting subjects were given either 1.05 mg atropine of 5.0 mg terbutaline orally. Pulmonary function was assessed using the peak responses, namely: three 60-minute intervals for terbutaline and three 30-minute intervals for atropine. A subgroup of five reactive bronchitis patients was given a placebo with no response. Areas under the percent response-time interval curve were compared. Both patient groups responded to the same degree to atropine and terbutaline with respect to reduction of airway resistance. However, the FEV1 and V50 responses to terbutaline were markedly enhanced compared to atropine in the asthmatics while equal to the atropine response in the bronchitis patients. Thus, atropine appears to exert its effect upon both large and small airways in bronchitis, but predominantly on large airways in asthma. The results are consistent with a state of enhanced vagal tone in small airways in bronchitis compared to asthma, but other explanations are conceivable.

Forty-eight children with known asthma (ranging in age from 2 to 16 years) were studied during an acute attack. Each received either terbutaline or epinephrine subcutaneously in a random double-blind fashion. Measurement of heart rate, respiratory rate, and systemic arterial systolic and diastolic blood pressures and careful clinical assessment of obstruction of the airway were made before and at 15, 30, and 60 minutes after the administration of the drugs. Appreciable and significant clinical improvement was noted in 19 of the 24 patients in both groups and was of comparable magnitude. A small, but significant, increase in heart rate was noted in those patients requiring only one injection of terbutaline, suggesting that the drug's selectivity for the lung is relative not absolute. The present study demonstrates that terbutaline is an effective bronchodilator drug in acute childhood asthma.

The effect of administration of terbutaline on the pulmonary and cardiovascular systems was studied in ten children with status asthmaticus. Terbutaline (0.01 to 0.04 mg/kg of body weight) was given subcutaneously in multiple doses. A significant decrease in respiratory rate and in arterial blood pressure, with no significant change in cardiac rate, was seen only after the first dose of terbutaline. There was a decrease in mean arterial carbon dioxide tension and an increase in mean arterial oxygen pressure. There was gross clinical improvement following administration of terbutaline in nine of the ten patients. One patient who failed to respond to administration of terbutaline also failed to respond to intravenously administered isoproterenol. We conclude that terbutaline is effective in the treatment of status asthmaticus, with only modest effects on the cardiovascular system.

Fenoterol hydrobromide (Berotec; formerly Th 1165a) is a sympathomimetic bronchodilator drug. Twenty subjects with mild to moderate reversible bronchospasm completed a double-blind multiple crossover study of single doses of 5 mg, 7.5 mg, and 10 mg of fenoterol hydrobromide, 24 mg of ephedrine, and placebo. Spirometric and body-plethysmographic measurements were performed sequentially prior to administration of drug or placebo and each hour up to eight hours afterwards. No significant drug-response relationship was noted for pulse rate or blood pressures, and side effects (eg, shakiness, nervousness) were minimal. Administration of fenoterol resulted in bronchodilation; a peak effect was noted at two to three hours after administration, and the duration of action was up to eight hours. A statistically significant dose-response relationship was observed; therapy with 5 mg of fenoterol hydrobromide was superior to placebo and equal to ephedrine, and doses of 7.5 mg and 10 mg of fenoterol hydrobromide were significantly better than placebo or ephedrine.

The control of asthma by therapy with cromolyn sodium was studied in 28 adults with late-onset asthma associated with hypersensitivity to aspirin and nasal polyps. Four-week periods of treatment with the drug or a placebo were compared in a double-blind crossover study. A subsequent eight-week open trial in 20 patients was compared to their period of receiving placebo. There was slight but significant improvement in the forced expiratory volume in one second (FEV1; P less than 0.05) and the mean forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%; P less than 0.05) after four weeks of therapy with cromolyn sodium and in the FEV1 (P less than 0.05), the forced vital capacity (P less than 0.01), and FEF25-75% (P less than 0.01) after an additional eight weeks of therapy with cromolyn sodium. The improvement in pulmonary function was not associated with changes in the peak expiratory flow rate, the symptoms of asthma, the doses of additional medication, or the index of disability. The dosage of corticosteroids in 22 patients receiving long-term therapy with steroids was no different between the four-week periods of treatment with placebo or drug but was significantly lower (P less than 0.05) during the eight-week open trial. We conclude that administration of cromolyn sodium has a therapeutic effect in this group of asthmatic patients.

The short-term effects of smoking one to three marihuana cigarettes (900 mg of marihuana per cigarette; 2.2% delta9-tetrahydrocannabinol) on left ventricular performance were evaluated in 21 experienced users of cannabis at different times during a 94-day in-hospital study of the biologic effect of daily heavy smoking of marihuana. In six subjects, cardiac output was determined using the indocyanine-green dye-dilution technique; and in two of these individuals and 15 additional subjects, cardiac output, ejection fraction, preejection period (PEP), left ventricular ejection time (LVET), and the velocity of circumferential fiber shortening (Vcf) were determined using echocardiograms, phonocardiograms, and carotid pulse recordings. Following the smoking of one to three marihuana cigarettes, the heart rate rose 16 to 53 percent, cardiac output rose 4 to 9 percent, stroke volume did not change or fell slightly, and ejection fraction, PEP/LVET, and did not change, except for a slight increase in Vcf (15%) after three marihuana cigarettes, which could be accounted for by the associated increase in heart rate (53%). These findings suggest that in long-term heavy users of cannabis, marihuana has no significant effect on myocardial contractility independent of its effect on heart rate.