Efficacy of buspirone in smoking cessation: a placebo-controlled trial.

Buspirone, a non-sedating anxiolytic, has yielded contradictory results in smoking cessation pilot studies and trials. We tested buspirone (n = 51) versus placebo (n = 49) in a placebo-controlled, double-blind trial of smoking cessation. Survival analyses were performed with use of strict abstinence criteria for efficacy (carbon monoxide levels < or = 8 ppm; no self-reported slips to smoking). No treatment differences were observed between active and placebo groups. There were also no differences among "anxiety" level groups formed post hoc from high versus low, pre-quit anxiety test scores. A number of withdrawal symptoms increased significantly after subjects quit smoking for both the active drug and placebo groups, but these symptoms were not relieved by treatment. There appears to be little evidence that buspirone is effective in smoking cessation or in the relief of withdrawal associated with cessation in a general sample. Selecting for generalized anxiety or anxiety related to cessation is suggested for future testing.

Respiratory and circulatory analysis of CO2 output during exercise in chronic heart failure.

BACKGROUND: The output of carbon dioxide (VCO2) is controlled by both hemodynamics and ventilation. To understand VCO2 in patients who have chronic heart failure (CHF), we studied 14 patients who had New York Heart Association functional class III failure by measurements of hemodynamics, ventilation, and arterial and venous blood gases at rest and at 50 W of cycle ergometry exercise. METHODS AND RESULTS: Fick principle analysis of VCO2 showed that because of a limited increase in cardiac output, CHF patients widened their venoarterial CO2 content difference from 4.9 +/- 3.5 ml/dl at rest to 11.1 +/- 4.0 ml/dl with exercise (p less than 0.05). This increase in CO2 content difference was achieved with no change in venous CO2 content (from 54.3 +/- 3.3 ml/dl at rest to 54.5 +/- 4.8 ml/dl at exercise, p = NS); however, there was a decrease of arterial CO2 content (from 49.4 +/- 3.7 ml/dl at rest to 43.4 +/- 2.3 ml/dl with exercise, p less than 0.05). Modeling of the CO2 tension-content relation showed that there would have been a small, nonproportional increase of venous CO2 content as venous CO2 tension increased from 43.2 +/- 1.8 mm Hg at rest to 55.3 +/- 4.2 mm Hg during exercise (p less than 0.05); however, the development of metabolic acidosis during exercise entirely blunted the increase of CO2 content. In contrast, both the shape of the tension-content relation and the acidosis of exercise further influenced the decrease of arterial CO2 content as arterial CO2 tension decreased from 37.0 +/- 2.9 mm Hg at rest to 32.0 +/- 3.4 mm Hg during exercise (p less than 0.05) as a result of excess ventilation. CONCLUSIONS: In CHF patients during exercise, the circulatory limitations imposed by a low cardiac output on VCO2 are compensated by a widened venoarterial CO2 content difference. The content difference is not widened through an increase of venous CO2 content but rather by a decrease of arterial CO2 content caused by arterial hypocapnia and metabolic acidosis.

Improvement in exercise performance after pulmonary arteriovenous malformation embolization.

Balloon or coil embolization has become established therapy for multiple PAVMs. We were able to evaluate a 32-year-old woman with multiple PAVMs characterized by significant orthodeoxia, intrapulmonary shunt, dyspnea and limited exercise tolerance before and after balloon and coil embolization. After embolization of three of her largest PAVMs, repeat evaluation revealed improvement in her symptoms, orthodeoxia and intrapulmonary shunt. She was able to exercise two additional work rates with a sustained improvement in oxygenation, a decrease in the P(A-a)O2 difference and higher maximum oxygen consumption. These studies provide objective evidence of persistent improvement in function and endurance at rest and during exercise after embolization.

Effect of breathing pattern on dead space ventilation VD/VT during exercise.

In order to assess the effect of breathing pattern on measurements of dead space ventilation (VD/VT) during exercise, we studied 6 patients with the complaint of exertional dyspnea. They had essentially normal resting pulmonary function studies and the only abnormality noted during an initial exercise study was an elevated VD/VT associated with a rapid respiratory rate. A second exercise study was then performed during which they were coached to breathe at a slower rate and larger tidal volume. During the exercise study with coaching, the VD/VT response was normal. We conclude that breathing pattern during exercise influences VD/VT and that an increase in total minute ventilation which is accomplished by a preferential increase in respiratory rate may result in an abnormally high VD/VT.

Ventilation and gas exchange during exercise in severe chronic heart failure.

Dyspnea and exercise limitation are ubiquitous symptoms in heart failure; the role of pulmonary factors has not been defined. We studied patients with severe left ventricular dysfunction at upright rest and during cycle ergometry. Arterial oxygen tension and saturation were normal at rest and exercise despite mild abnormalities in Qs/Qt and P(A-a)O2, as well as the effects of low S-vO2. Ventilation was increased at rest and exercise because of increased VD/VT and alveolar hyperventilation. The basis of these abnormalities is unknown. We concluded that when considering the symptoms of dyspnea and exercise limitation, arterial oxygenation is probably not important, but excessive ventilation may be a contributing factor.

Effects of beta-adrenergic blockade on ventilation and gas exchange during exercise in humans.

The effects of beta-adrenergic blockade induced by intravenous propranolol hydrochloride (0.2 mg/kg) on ventilatory and gas exchange responses to exercise were studied during tests in which the work rate was either increased progressively or maintained at a constant load in six healthy young male subjects. Heart rate during exercise decreased by about 20% and cardiac output, as estimated by a modification of the method of Kim et al. (J. Appl. Physiol. 21: 1338-1344, 1966), by about 15%. The relation between work rate and O2 uptake (VO2) was unaffected by propranolol, whereas maximal O2 uptake (VO2max) decreased by 5% and the anaerobic threshold, estimated noninvasively, was lowered by 23%. The relations between CO2 output (VCO2) and end-tidal CO2 partial pressure (PCO2) and between VCO2 and minute ventilation (VE) were both unaffected. The time constants for changes of VO2, VCO2, and VE during on-transients from unloaded pedaling to either a moderate (ca. 50% VO2max) or a heavy (ca. 67% VO2max) work rate in the control studies were in agreement with previously reported values, i.e., 42, 60, and 69 s, respectively. beta-Blockade was associated with a significantly increased time constant for VO2 of 61 s but with less consistent and insignificant changes for VCO2 and VE. There was a small but significant increase of the time constant for heart rate from 40 to 45 s. It is concluded that propranolol exerts its primary influence during exercise on the cardiovascular system without any discernible effect on ventilatory control.

Sensitive indices of improvement in a pulmonary rehabilitation program.

It is often difficult to demonstrate objective evidence of physiologic improvement following a pulmonary rehabilitation program, despite subjective increases in exercise tolerance. In an attempt to identify sensitive indices of improvement, we studied resting and exercise lung function extensively in 15 patients (age range 45 to 73) with severe chronic obstructive lung disease before and after a pulmonary rehabilitation program. The six-week outpatient rehabilitation program consisted of exercise at 70 percent of the maximum predicted heart rate and diaphragmatic breathing for 20 minutes three times weekly. There were no significant changes in resting pulmonary function following exercise training. Exercise measurements were unchanged after completion of the program, with the exception of two parameters: heart rate and arterial lactate levels. The observed small but significant reductions in exercise heart rate and blood lactate levels following training may be due to conditioning of skeletal muscles, although respiratory muscle conditioning may be a contributing factor. Measurements of blood lactate may be a useful marker of conditioning in patients with chronic obstructive pulmonary disease who complete a pulmonary rehabilitation program.

Computerized body plethysmography: an algorithm for minimizing drift and hysteresis.

The use of linear regression for on-line data processing of airway resistance measurements in the body plethysmograph may be difficult. When airflow (V) is plotted against plethysmographic pressure (Pbox), the resulting loop exhibits hysteresis and may drift along the PBox axis. Although the slope of the V-PBox loop can be estimated visually, computer calculations of the slope are difficult if baseline drift is present. Taking the derivatives of V and PBox eliminates the effect of drift and reduces the loops to a series of essentially parallel lines from which the slope can be readily calculated using linear regression. The identical technique can be employed when mouth pressure is plotted against plethysmographic pressure, enabling on-line calculation of thoracic gas volume.

Role of exercise testing in assessing functional respiratory impairment due to asbestos exposure.

To evaluate the complaint of exertional dyspnea in asbestos-exposed shipyard workers, pulmonary function tests were performed at rest and during exercise on 90 subjects with pleural plaques. We divided the subjects into four groups based on resting pulmonary function studies. Group I subjects (eight) had a restrictive defect; group II subjects (30) had an obstructive defect; group III subjects (six) had an isolated reduction in diffusing capacity; and group IV subjects (46) had a normal study. Subjects with a restrictive defect demonstrated minor physiologic abnormalities during exercise. Subjects with an obstructive defect demonstrated abnormalities consistent with their obstructive defect. Subjects in groups III and IV demonstrated an abnormally elevated wasted ventilation fraction, which may be an early indicator of interstitial disease due to asbestos exposure. We believe exercise testing was a useful tool in excluding the presence of significant functional exercise limitation due to asbestos exposure in the majority of subjects and also in disclosing some physiologic abnormalities in some of the subjects in our study.

Arterial oxygenation and arterial oxygen transport in chronic myocardial failure at rest, during exercise and after hydralazine treatment.

Arterial oxygen transport (cardiac output x arterial oxygen content) may be decreased in heart failure. We studied the determinants of arterial oxygen transport in 15 patients with chronic, severe myocardial failure at rest and during cycle ergometry. During control therapy at rest, arterial oxygen tension was normal (81 +/- 8 mm Hg, mean +/- SD) and increased slightly during exercise (90 +/- 14 mm Hg). During hydralazine therapy at rest, arterial oxygen tension was slightly higher (87 +/- 9 mm Hg) and also increased during exercise (92 +/- 15 mm Hg). Hydralazine did not increase arterial oxygen tension (0.10 greater than p greater than 0.05), but exercise did (p less than 0.02). Arterial oxygen saturation and content were normal and did not change under any condition or treatment. During control therapy at rest, arterial oxygen transport was low (313 +/- 74 ml/min . m2) and remained abnormally low during exercise (434 +/- 124 ml/min . m2). During hydralazine therapy, arterial oxygen transport was higher at rest (457 +/- 100 ml/min . m2) and during exercise (577 +/- 131 ml/min . m2). Hydralazine increased arterial oxygen transport (p less than 0.01) because it increased stroke volume at rest and during exercise, but it did not change arterial oxygenation. Arterial oxygenation is normal in chronic heart failure patients at rest and during exercise. Hydralazine increases cardiac output and arterial oxygen transport without changing arterial oxygenation.

Abnormal wasted ventilation fraction and normal pulmonary hemodynamics during exercise in patients with exertional dyspnea.

We have previously reported a drop on wasted ventilation fraction (VD/VT) during exercise in patients with pulmonary vaso-occlusive diseases associated with collagen vascular disorders, despite an abnormally high mean pulmonary artery pressure and pulmonary vascular resistance at rest and during exercise. To further evaluate the diagnostic value of VD/VT measurements, we studied 8 subjects with normal spirometry, lung volumes and single-breath diffusing capacity who had previously demonstrated a high VD/VT at rest and during exercise. We found normal pulmonary hemodynamics in these subjects despite an abnormal rest and exercise VD/VT. Our findings effectively exclude hemodynamically significant pulmonary vascular obstruction, and do not support the use of VD/VT as a screening method for detecting diffuse pulmonary vaso-occlusive diseases.

Exercise performance in chronic obstructive pulmonary diseases.

Patients with chronic obstructive pulmonary diseases demonstrate exercise limitation as a consequence of both an increased ventilatory requirement and a decreased ventilatory capacity. The increased ventilatory requirement arises from the elevated wasted ventilation fraction of each breath (VD/VT) and hypoxemia secondary to ventilation-perfusion mismatching, both of which stimulate minute ventilation of increase. The reduced ventilatory capacity is primarily the result of airflow obstruction, which causes an increased work of breathing. Respiratory muscle fatigue may also play a role in reducing ventilatory capacity. The differentiation of heart failure from chronic obstructive pulmonary diseases as a cause of dyspnea can be accomplished using a variety of noninvasive and invasive techniques during exercise, including measurements of minute ventilation, the expiratory airflow pattern, ventilatory reserve (VEmax/MVV), ventilatory efficiency (VD/VT), arterial blood gases, the anaerobic threshold, heart rate, cardiac output, pulmonary hemodynamics and ventricular ejection fraction. Exercise training of patients with chronic obstructive pulmonary diseases improves exercise intolerance but appears to have little effect on pulmonary function tests, arterial blood gases and pulmonary hemodynamics. Supplemental oxygen during exercise training may be a useful adjunct for improving exercise tolerance in patients with chronic obstructive pulmonary diseases.

Post-pneumonectomy syndrome. Surgical correction using Silastic implants.

A post-right pneumonectomy syndrome is described which manifests symptoms of exertional dyspnea and inspiratory stridor on rapid inspiration. These symptoms were associated with marked rightward and posterior deviation of the trachea, over-distention of the left lung with its herniation into the right side of the chest and kinking of the left lower lobe bronchus. At the time of surgery, the tracheal deviation, lung herniation and the kink in the left lower lobe bronchus were immediately corrected by releasing the adhesions between the malpositioned structures and the right chest wall. To maintain the corrected positions, Silastic implants totalling a volume of 990 ml were placed into the space created in the right chest. Following surgery, exertional dyspnea was present with only extraordinary activity, and inspiratory stridor was eliminated. The patient remains asymptomatic three years following surgical correction, and is able to carry on a normal and productive life. We conclude that a syndrome associated with marked exertional dyspnea and inspiratory stridor might develop in situations of marked tracheal shift and overdistention of the remaining lung following right pneumonectomy.

Evaluation of an oxygen concentrator in patients with COPD.

The value of a new oxygen concentrator was investigated in 20 patients with COPD. The oxygenating ability of the device was compared to that of piped-in oxygen at flows of 1, 2, 4, 6, 8, and 10 l/min by measuring arterial blood gases after 14 min of breathing through a nasal cannula. For flows up to 4 l/min, the concentrator produced increases in PaO2 that were comparable to the increases resulting from piped-in oxygen. At higher flows, the PaO2 achieved by each flow of 6-10 l/min was significantly less when using the concentrator as compared to piped-in oxygen. The device was reliable, easy to use, and well accepted. It was concluded that the concentrator provides a useful alternative to piped-in oxygen or cylinders of oxygen for patients requiring flows of up to 4 l/min.

Effect of beta-adrenergic blockade during exercise on ventilation and gas exchange.

The ventilatory effects of beta-adrenergic blockade during steady-state exercise were studied in eight normal subjects using intravenous propranolol hydrochloride (0.2 mg/kg). Heart rate decreased in all subjects by an average of 17%. Coincident with the phase of decreasing heart rate was a significant decrease in both minute ventilation (VE) and CO2 output (VCO2), averaging 9.6 and 9.2%, respectively. Both functions returned to prepropranolol levels after heart rate had reached its reduced steady-state value. The change in VE was significantly correlated with the change in VCO2 (r = 0.85, P less than 0.005), and was associated with negligible changes in endtidal CO2 tensions and ventilatory equivalents for CO2. We interpret these studies as showing that the transient isocapnic hypopnea concomitant with an acute reduction in cardiac output was secondary to a transient decrease in CO2 flux (cardiac output x mixed venous CO2 content). This decrease in VE appears to be induced by the acute decrease in cardiac output ("cardiodynamic hypopnea"), in fashion similar to the previously described cardiodynamic hyperpnea.