Gas exchange during exercise in healthy people II. Venous admixture

1. Venous admixture/cardiac output ratio (Qva/Qt) has been measured in twenty-four healthy volunteer subjects of both sexes aged 20-71 years, at rest and during the steady state of treadmill exercise at two rates of work, and breathing air and breathing oxygen. 2. With oxygen breathing, Qva/Qt was considerably less during exercise than during the time subjects were taking either normal or deep breaths of oxygen at rest, and did not significantly increase with the intensity of exercise. It is postulated that the increase in ventilation during exercise opens most or all of those alveoli which, during oxygen breathing at rest, close because of critically low ventilation/perfusion (V/Q) ratios. 3. With air breathing, Qva/Qt fell from rest to exercise (especially in older subjects), presumably due to improved ventilation of alveoli at the lung bases. With an increase in work rate Qva/Qt increased in all age groups. This increase was not due to increase in the shunt fraction (Qs/Qt), nor to limitation of diffusing capacity; it arose from an increase in V/Q variance. 4. Equations have been derived for the prediction of normal Qva/Qt during exercise, with or without correction for the effects of increasing pulmonary capillary temperature. These effects do not materially influence the accuracy of prediction, but may be relevant to some of the interpretations. In particular, they provide a further indication that Qs/Qt probably cannot be measured by breathing oxygen at rest, even in deep breathing.     

Pressure-flow-volume relationships in pulmonary circulation of normal highlanders

Pulmonary vascular pressures and blood flow were measured with and without unilateral pulmonary arterial occlusion (UPAO) at rest and during exercise in 10 normal highlanders at La Paz, Bolivia (altitude, 3,750 m). In 6 other highlanders at rest and during exercise, pulmonary pressures, flow, and blood volume were measured during air breathing (PIO2 congruent to 100 Torr) and 29-30% oxygen (PIO2 congruent to 150 Torr). During air breathing, pulmonary vascular resistance was elevated at rest and did not change with exercise. Pulmonary arterial pressure rose less at rest with UPAO than during exercise without UPAO, and pulmonary vascular resistance was less in the former. Raising PaO2 to normal sea-level values had no effects on the pulmonary circulation at rest but prevented to a large extent the rise in pulmonary arterial pressure during exercise. Hence pulmonary vascular resistance during exercise was lower with oxygen than without. Thus, hypoxic vasoconstriction contributed to the pulmonary hypertension during exercise in normal highlanders. Circumstantial evidence suggests that this is related to the profound mixed venous hypoxemia caused by exercise in a hypoxic environment.     

Training with supplemental oxygen in patients with COPD and hypoxaemia at peak exercise

Supplemental oxygen has acute beneficial effects on exercise performance in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate whether oxygen-supplemented training enhances the effects of training while breathing room air in patients with severe COPD. A randomized controlled trial was performed in 24 patients with severe COPD who developed hypoxaemia during incremental cycle exercise (arterial oxygen saturation (Sa,O2) <90% at peak exercise). All patients participated in an in-patient pulmonary rehabilitation programme of 10 weeks duration. They were assigned either to general exercise training while breathing room air (GET/RA group: forced expiratory volume in one second (FEV1) 38% of predicted; arterial oxygen tension (Pa,O2) 10.5 kPa at rest; Pa,O2 7.3 kPa at peak exercise), or to GET while breathing supplemental oxygen (GET/O2 group: FEV1 29% pred; Pa,O2 10.2 kPa at rest; Pa,O2 7.2 kPa at peak exercise). Sa,O2 was not allowed to fall below 90% during the training. The effects on exercise performance while breathing air and oxygen, and on quality of life were compared. Maximum workload (Wmax) significantly increased in the GET/RA group (mean (SD) 17 (15) W, p<0.01), but not in the GET/O2 group (7 (25) W). Six minute walking distance (6MWD), stair-climbing, weight-lifting exercise (all while breathing room air) and quality of life significantly increased in both groups. Acute administration of oxygen improved exercise performance before and after training. Training significantly increased Wmax, peak carbon dioxide production (V'CO2) and 6MWD while breathing oxygen in both groups. Differences between groups were not significant. Pulmonary rehabilitation improved exercise performance and quality of life in both groups. Supplementation of oxygen during the training did not add to the effects of training on room air.     

Does cold air affect exercise capacity and dyspnea in stable chronic obstructive pulmonary disease?

Cold air may worsen asthmatic bronchoconstriction but can lessen breathlessness in normal individuals. Patients with COPD sometimes report improvement in their dyspnea in cold weather. We examined the effect of breathing cold air on exercise tolerance and the perception of breathlessness in 19 patients with stable COPD (age [+/- SD], 63 +/- 6 years; FEV1, 0.99 +/- 0.28 L) in a randomized open study. Patients exercised on a cycle ergometer breathing either room or cold air (-13 degrees C), breathlessness being assessed by Borg scaling. Peak exercise performance improved when breathing cold air (mean +/- SE), 46 +/- 6 W compared with 37 +/- 7 W (p < 0.05) while end-exercise breathlessness fell from 4.6 +/- 0.4 compared with 4.1 +/- 0.5 (p < 0.05) when breathing cold air. End-exercise ETCO2 was higher breathing cold air (6.1 +/- 0.3 kPa compared with 5.5 +/- 0.3 kPa) (p < 0.005). There was no difference in breathlessness at equivalent levels of ventilation. Cold air reduces breathlessness in COPD, probably by inducing relative hypoventilation.     

Effects of increased O2-N2 pressure and breathing apparatus on respiratory function

The ventilatory response of four subjects was measured at rest and various intensities of exercise. Experiments were conducted in a dry pressure chamber (1) at 1 ATA and 4 ATA with the subjects breathing from a low-resistance mouthpiece, and (2) at ATA with the subjects breathing from open-circuit breathing apparatus (Royal Naval Swimmers' Air Breathing Apparatus). At 4 ATA there was significant hypoventilation and hypercapnia, together with an increased tidal volume and lower respiratory frequency. The use of the breathing apparatus tended to amplify these changes in ventilatory response. In addition, the extent of hypercapnia at 4 ATA was related to the exercise intensity. When subjects breathed from a low-resistance mouthpiece, oxygen uptake was significantly greater at 4 ATA than at the surface for the same ergometric work load, but when they breathed from the breathing apparatus, the increase in oxygen uptake was not significant in comparison to surface values. At 4 ATA bradycardia was evident at all levels of exercise but was not affected significantly by the presence of the breathing apparatus.     

Near-infrared spectroscopy for monitoring of tissue oxygenation of exercising skeletal muscle in a chronic compartment syndrome model

Variations in the levels of muscle hemoglobin and of myoglobin oxygen saturation can be detected non-invasively with near-infrared spectroscopy. This technique could be applied to the diagnosis of chronic compartment syndrome, in which invasive testing has shown increased intramuscular pressure associated with ischemia and pain during exercise. We simulated chronic compartment syndrome in ten healthy subjects (seven men and three women) by applying external compression, through a wide inflatable cuff, to increase the intramuscular pressure in the anterior compartment of the leg. The tissue oxygenation of the tibialis anterior muscle was measured with near-infrared spectroscopy during gradual inflation of the cuff to a pressure of forty millimeters of mercury (5.33 kilopascals) during fourteen minutes of cyclic isokinetic dorsiflexion and plantar flexion of the ankle. The subjects exercised with and without external compression. The data on tissue oxygenation for each subject then were normalized to a scale of 100 per cent (the baseline value, or the value at rest) to 0 per cent (the physiological minimum, or the level of oxygenation achieved by exercise to exhaustion during arterial occlusion of the lower extremity). With external compression, tissue oxygenation declined at a rate of 1.4 +/- 0.3 per cent per minute (mean and standard error) during exercise. After an initial decrease at the onset, tissue oxygenation did not decline during exercise without compression. The recovery of tissue oxygenation after exercise was twice as slow with compression (2.5 +/- 0.6 minutes) than it was without the use of compression (1.3 +/- 0.2 minutes).     

Effects of acute passive smoking on exercise-induced bronchoconstriction in asthmatic children

This study was designed to investigate the acute effects of environmental tobacco smoke (ETS) in children with mild asthma during rest and exercise. We studied 13 children [8 males, 5 females; mean age 10 (range 8-13) yr; mean forced expired volume in 1 s (FEV1) 93% (range 82-108%) of predicted] with exercise-induced bronchoconstriction [46 +/- 4% (SE) fall in FEV1 after exercise during cold air breathing]. Children were exposed to ETS (20 ppm carbon monoxide) or ambient air (AA) for 1 h. During the first 54 min of exposure, children were at rest, and during the last 6 min they exercised on a bicycle ergometer (2 W/kg body wt). Spirometry was performed before and during exposure and after exercise. Respiratory symptoms were recorded before and after exposures. In seven children the experiments with AA and ETS were done in duplicate. FEV1 between 5 and 54 min of exposure at rest decreased by 3.2 +/- 0.8% (SE) during AA and by 7.2 +/- 2.3% during ETS exposure compared with preexposure values; the difference between AA and ETS was statistically significant (P = 0.04). The drop in FEV1 was achieved within 5 min and did not change with ongoing exposure. Analysis of individual data revealed that the mean changes during ETS were mainly effected by three children with a significant fall and one child with a significant improvement in FEV1 (P < 0.05). Maximum postexercise fall of FEV1 was 25 +/- 4% after AA and 24 +/- 3% after ETS, which did not differ significantly. Upper and lower respiratory tract symptoms were not significantly different between exposures.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pharmacologic effect of aerosolized terbutaline sulfate in exercise-induced bronchospasm

Bronchospasm can be induced in asthmatics when exercised according to a multistage branching treadmill protocol that allows them to achieve 80 per cent of maximal age-predicted heart rate. This degree of exercise is usually achievable and allows inducible bronchospasm to occur. This present study was undertaken to investigate the effect of terbutaline sulfate aerosol in exercise-induced broncho-spasm. Asthmatics were exercised to 80 per cent of their maximal heart rate, and FEV1.0 and MMEFR were assessed while standing using a Jones Pulmonar II waterless spirometer at 5, 15, and 30 minutes after exercise. After a standard rest period defined by a return to baseline of FEV1.0, MMEFR, and heart rate for 30 minutes, the subjects were administered either 0.50 mg aerosolized terbutaline sulfate or placebo and then exercised again. The pulmonary function parameters were again recorded after this exercise. Preterbutaline and postplacebo exercise resulted in a significant reduction in FEV1.0 and MMEFR, while after treatment with terbutaline not only did bronchospasm not occur but bronchodilation occurred (P less than 0.01). Inhaled terbutaline appeared to normalize the exercise tolerance of the asthmatics and restore physiologic pulmonary airway conductance according to the parameters of FEV1.0 and MMEFR.     

Carbon monoxide and water vapor contamination of compressed breathing air for firefighters and divers

Compressed breathing air, used in self-contained breathing apparatus (SCBA) by firefighters and other categories of workers as well as by recreational and commercial divers, is prepared with the aid of high-pressure compressors operating in the range of 5000 psig. There have been reports of unexplained deaths of SCUBA divers and anecdotal accounts of decreased time to exhaustion in firefighters using SCBAs. Compressed breathing air has been found to contain elevated levels of carbon monoxide (CO) and water vapor that are consistent with carboxyhemoglobin (COHb) poisoning and freezing of the user's regulator on the breathing apparatus. The Coburn-Forster-Kane equation (CFK equation) was used to estimate COHb levels at rest and at maximum exercise when exposed to different levels of CO in contaminated breathing air. The results demonstrated that, at maximum exercise, the COHb ranged from 6.0 to 17% with the use of 1 to 4 SCBA cylinders contaminated by 250 ppm CO. Standard operating procedures have been developed at the Montreal Fire Department to minimize the risk of compressed breathing air contamination. Results of the quality analysis/quality control program indicate that implementation of these procedures has improved the quality of the compressed breathing air. Recommendations are made for improvement of the air testing procedures mandated by the Canadian CAN3 180.1-M85 Standard on Compressed Breathing Air and Systems.     

Kinetics of VO2 and VCO2 in the horse and comparison of five methods for determination of maximum oxygen uptake

To determine whether maximum oxygen uptake (VO2max) in the horse in influenced by type of exercise test, five different protocols were evaluated in eight untrained Thoroughbreds exercised on a treadmill. With all protocols, horses were given a 5 min warm-up on a 10 per cent treadmill slope. Three protocols were at a 10 per cent slope and included: 1) increasing the running speed by 1 to 2 m/sec every 60 secs from 4 m/sec to a maximum of 12 m/sec; 2) running at 12 m/sec until fatigue; and 3) running for 3 to 4 mins at speeds ranging from 6 to 12 m/sec with rest pauses between exercise bouts. The fourth protocol employed a 24 per cent slope where animals exercised for 5 mins at 2 m/sec followed by 3 mins at 5 m/sec, and 2 mins at 6 m/sec. The fifth test involved running at 11 m/sec while the slope of the surface was increased every 2 mins until the horses could not maintain the pace. A plateau in VO2 occurred in all protocols except when exercise was performed on a 24 per cent slope. Slow speed exercise at a steep grade (24 per cent) produced the highest VO2 (P < 0.05) even though there was no plateau in the VO2. A steady state for VO2 and VCO2 existed 90 secs after the onset of exercise with all protocols which involved 2 mins or more at each speed. The VO2 and VCO2 values at all speeds of the rapid incremental exercise test were not different to those found at steady state in the third exercise protocol.     

Xenon effects on regional cerebral blood flow assessed by 15O-H2O positron emission tomography: implications for hyperpolarized xenon MRI

Subjective and physiologic effects of 33% inhaled Xe were measured with 15O-water positron emission tomography (PET) in 3 subjects at rest and during visual stimulation. The procedure was well tolerated. Robust functional activations of the visual cortex were obtained after xenon (Xe) inhalation as well as air breathing. However, Xe inhalation was followed by smaller size, but significant decreases of regional cerebral blood flow (rCBF) in visual cortex relative to the air-breathing baseline, both during visual stimulation and at rest. No such decreases were found in other sensory or motor regions.     

An additive effect of cold exposure and hypoxia on pulmonary artery pressure in sheep

When shorn sheep were exposed to cold (3 degrees C) pulmonary artery pressure (PPA) increased by 24 per cent. When they were caused to breathe an air mixture containing only 11 per cent oxygen there was a similar rise in PPA (27 per cent). During simultaneous exposure to 3 degrees C and low oxygen tension, the rise in PPA was greater than the sum of the two separate treatments (61 per cent). These results indicate the possible significance of cold exposure in the occurrence of high mountain sickness.     

The effect of active movement of the foot on venous blood flow after total hip replacement

Surgeons often encourage patients to move their feet in an attempt to prevent venous stasis, but there is little evidence that this measure is beneficial. We investigated the effect of active movement of one foot on the venous blood flow four days after total hip replacement. The actual venous outflow at rest was measured with use of venous occlusion strain-gauge plethysmography in thirty-eight patients. The patients were randomly allocated to the control group (eighteen patients) or the exercise group (twenty patients). A baseline measurement was followed by a one-minute period of rest (control group) or of maximum plantar flexion and dorsiflexion of the foot, ankle, and toes at a rate of thirty cycles per minute (exercise group). The venous outflow was measured again at two, seven, twelve, and thirty minutes in both groups. Movement of the foot for one minute produced a significant and sustained increase (p < 0.002) in the venous outflow (mean maximum increase, 22 per cent). The value remained greater than the baseline level for thirty minutes (mean increase, 6.5 per cent) (p < 0.2). The increase was gradual, reaching a maximum twelve minutes after the completion of exercise. Our results confirm the beneficial hemodynamic effects of active movement of the foot in the postoperative period and suggest that patients should move the feet and ankles postoperatively as part of a prophylactic regimen directed at decreasing the risk of venous thrombosis.     

Detection of nivalenol genotoxicity in cultured cells and multiple mouse organs by the alkaline single-cell gel electrophoresis assay

The effects of upper airway (UAW) flows and pressures on breathing pattern and respiratory muscle activities were studied in anesthetized rats breathing through a tracheostomy. A steady flow (approximately 1000 ml/kg/min) of cold dry air, or cold wet air, or warm wet air was passed through the UAW, in the expiratory direction for approximately 20 sec (20-40 sec). In other trials positive or negative pressure was applied to the isolated UAW for a similar duration. There was a marked prolongation of the expiratory duration and decreases in peak inspiratory flow, tidal volume, and peak diaphragm electromyogram (EMG) activity in response to cold dry airflow. The responses to cold wet air were reduced but still significant. Warm wet air had no effect on breathing. These responses show that UAW cooling and drying depress breathing in the rat and that cooling itself could cause the inhibition of breathing. Negative pressure induced substantial increases in genioglossus and laryngeal inspiratory activity while positive pressure caused a decrease in genioglossus activity. Positive pressure also increased expiratory time while negative pressure increased inspiratory time. These results confirm the functional role of the UAW dilating muscles in preventing UAW from collapse in rats.     

Oxygen-dependent circulation of sickle erythrocytes

The effects of in vivo hyperoxia and hypoxia on the intravascular survival of 51Cr-labeled human sickle erythrocytes (SS RBS's) were studied after transfusion into rats and guinea pigs. The function of these animals' reticuloendothelial and complement systems had been previously inhibited by ethyl palmitate and cobra venom factor, thus allowing extension of the survival of the heterologous human RBC's. In the blood of rats breathing ambient air the 51Cr half-life survival of RBC's from 11 patients with sickle-cell anemia (mean, 7.1 hours; range, 2.0 to 16.5 hours) was significantly shorter (p less than 0.001) than that of five control subjects (mean, 17.5 hours; range, 12.0 to 26.5 hours). When rats transfused with sickle RBC's were exposed to 100 per cent O2, a mean increment of 16.5 per cent blood 51Cr activity was observed within the first 15 to 60 minutes of hyperoxia. Subsequent oxygen deprivation (7 to 8 per cent O2) resulted in an equally rapid decrease (mean, 35.6 per cent) in blood 51Cr activity. Continuation of hypoxia for up to 17 hours did not cause further acceleration of 51Cr activity. Continuation of hypoxia for up to 17 hours did not cause further acceleration of 51 Cr RBC clearance. Under these conditions the slope of the sickle RBC survival curve was similar to that in animals kept in ambient air. After hypoxic rats were allowed to breate room air again, mean 51Cr blood activity increased by 41.7 per cent. Sickle RBC's transfused to guinea pigs exhibited similar oxygen-dependent survival characteristics. The survival of 51Cr RBC's from four adult control subjects and of unlabeled fetal RBC's from three human cord blood samples was unaffected by oxygen changes. When rats that had been transfused with sickle reticulocytes labeled in vitro with 59Fe were made hypoxic, a decrease in blood 59Fe activity was observed. The extent of this decrease was comparable to that in rats transfused with 51Cr labeled RBC's from the same patients. There was increased liver and spleen 51Cr activity in animals transfused with 51Cr SS RBC's and killed during hypoxia when compared to that of hyperoxic animals. These studies suggest that a minor population of sickle cells is removed from circulation during hypoxia and circulates again upon reoxygenation of the animals. Erythrocyte aging does not appear to be responsible for this phenomenon. The oxygen-depdendent circulation of a population of SS RBC's in this animal system is probably due to reversible sickling and trapping of sickled cells in the microcirculation.     

Nasal inhalation of l-menthol reduces respiratory discomfort associated with loaded breathing

To test the hypothesis that stimulation of cold receptors in the upper airway may alleviate the sensation of respiratory discomfort, we investigated the effects of nasal inhalation of l-menthol (a specific stimulant of cold receptors) on the respiratory sensation and ventilation during the loaded breathing in 11 normal subjects. Subjects were asked to rate their sensation of respiratory discomfort using a visual analog scale (VAS) while breathing on a device with a flow-resistive load (180 cm H2O/L/s) or with an elastic load (75.5 cm H2O/L). The effects of inhalation of l-menthol on ventilation and respiratory sensation were evaluated by comparing the steady-state values of ventilatory variables and VAS scores obtained before, during, and after l-menthol inhalation. In 8 of 11 subjects inhalation of strawberry-flavored air instead of l-menthol was performed during loaded breathing. Both during the flow-resistive loading and the elastic loading, inhalation of l-menthol caused a significant reduction in sensation of respiratory discomfort (flow-resistive loading: 62 +/- 14 [mean +/- SD] VAS units before inhalation versus 36 +/- 16 during inhalation, p < 0.01; elastic loading: 68 +/- 13 before inhalation versus 55 +/- 17 during inhalation, p < 0.01) without a significant change in breathing pattern and ventilation. Comparison of the effects between the flow-resistive loading and the elastic loading also revealed that the reduction in VAS score was more during the flow-resistive loading than during the elastic loading (p < 0.01). Inhalation of strawberry-flavored air caused neither changes in VAS score nor changes in breathing pattern and ventilation, indicating that olfaction is not a contributing factor in the relief of respiratory discomfort. We concluded that stimulation of cold receptors in the upper airway with nasal inhalation of l-menthol reduces the sensation of respiratory discomfort associated with loaded breathing. This effect is more effective during the flow-resistive loading than during the elastic loading.     

Respiratory responses to exercise in divers at 0.4 MPa ambient air pressure

OBJECT: This study was carried out to evaluate changes in the breathing pattern of divers during exercise at an elevated ambient air pressure equivalent to a depth of 30 m of seawater. METHODS: A total of 22 healthy male subjects performed graded bicycle exercise in a dry hyperbaric chamber up to a maximum of 3.5 W kg(-1) body weight at normal (0.1 MPa) and at elevated ambient air pressure (0.4 MPa). The exercise ventilation (VE), tidal volume (VT), breathing frequency (BF), oxygen uptake (VO2), carbon dioxide elimination (VCO2), and heart rate (HR) were measured. Perceived dyspnea was assessed by Borg scale ratings. RESULTS: Comparison of respiratory indices between conditions (0.1 versus 0.4 MPa) revealed a significant reduction in VE, VT, BF, and HR during exercise at 0.4 MPa. VO2 and VCO2 did not differ significantly between conditions. Likewise, no significant difference between conditions emerged in perceived dyspnea. CONCLUSION: Ventilation is significantly impaired during heavy bicycle exercise at 0.4 MPa. This is obviously not apparent with regard to subjective perception of dyspnea.     

Elevated arterial pressure and postexertional ST-segment depression in middle-aged women

Of ten healthy women, 43 to 61 years of age, four exhibited 1 mm. or more of upsloping ST-segment depression after maximal exercise, using the Bruce multistage treadmill protocol; the other six did not. Cardiac output (direct Fick) was not different in the two groups, wither at rest or during exercise. The women with ST-positive responses were older (56 vs. 51 years) and heavier (relative weights 109 per cent vs. 102 per cent), and their resting mean systemic pressures were higher. Their systemic and pulmonary mean arterial pressures during the last five minutes of upright exercise were significantly higher (P less than 0.001) than those in the ST-negative group. Although the ratio of systemic to pulmonary mean arterial pressures was higher at rest, it progressively fell during exercise in the ST-positive group. Polarcardiographic display of the Frank ECG during the first 3 minutes of recovery after maximal exercise showed significant differences between the ST and T of the two groups. At initial recovery, MS-phi greatly exceeded 10.6 mV. which is sensitive PCG ischemic exercise criterion in the ST-positive group. Although the number of observations is limited, it is concluded that greater hemodynamic stress imposed on the subendocardium by elevated pressures, rather than by any significant functional evidence of restriction in coronary blood flow, probably explains much of the postexertional ST-segment depression after maximal exercise.     

Recovery of ventilatory response to carbon dioxide after thiopentone, morphine and fentanyl in man

Ventilatory responses to CO2 (delta VI/delta PCO2) were measured half, one, two and four hours after infusions of thiopentone, morphine, fentanyl and saline in healthy men in order to test the idea that variation in clinical recovery and control of breathing after anaesthetic drugs are associated with interindividual differences in control measurements of delta VI/delta PCO2. Ventilatory response to CO2 was profoundly reduced one half hour after each drug, in contrast to the observation during air breathing that ventilation and end tidal PCO2 had returned to within 10 per cent of control. Mean delta VI/delta PCO2 increased progressively at one, two, and four hours, returning to near control after thiopentone, but remaining less than 80 per cent of control four hours after morphine and fentanyl. From the regression equations of each ventilatory response, ventilation at PCO2 of 58 and 70 mmHg (VI58 and VI70) were computed to estimate displacement of the response curves by the drugs. Following thiopentone there was no significant change of V158. In contrast ther was a highly siginificant fall of VI58 one half hour after fentanyl (p less than 0.01), with progressive return towards control at one, two, and four hours; similar changes were observed after morphine. For each drug, changes of VI70 were substantially greater than corresponding changes of V158. At all times during these recovery measurements, subjects were conscious and co-operative and, by traditional clinical criteria, were judged to have recovered from the effects of the drugs. Differences between high and low responding subjects were assessed by plotting control measurements against values obtained half and one hour after drugs. No systematic differences were found. These findings suggest that delta VI/delta PCO2 is a sensitive indicator of central nervous activity, but do not support the concepts that individuals with low delta VI/delta PCO2 might be more susceptible to the ventilatory depressant effects of anaesthetic drugs, or that low delta VI/delta PCO2 might be associated with delayed return of spontaneous breathing after general anaesthesia. Plasma thiopentone levels at half, one, and four hours were highly reproducible, in contrast to the wide variation of delta VI/delta PCO2 among subjects in this study. These findings together support the notion that wide variation in clinical recovery from anaesthesia may have a primary physiological basis in addition to variation caused by interindividual differences in drug dosage, biotransformation and excretion.     

Beta-adrenergic blockade as adjunctive oral therapy in patients with chronic atrial fibrillation

In many patients with chronic atrial fibrillation, it is difficult to prevent an excessive ventricular rate under stress, even with high levels of digoxin in the blood. The effect of adding beta-adrenergic blockade with practolol to digoxin on the heart rate at rest and during low-grade controlled exercise was investigated in 28 patients with chronic atrial fibrillation and in ten normal control subjects who were receiving maintenance dosages (0.25 to 0.75 mg) of digoxin. In atrial fibrillation, therapy with practolol decreased the mean heart rate at rest from 99.8 beats per minute to 77.5 beats per minute (23 percent reduction; P less than 0.01) and during mild exercise from 148.9 beats per minute to 105.4 beats per minute (29 percent) reduction (P less than 0.001). Fifteen patients had clinically significant heart failure; therapy with practolol did not worsen it. Reversible side effects were detected in two patients. When therapy with digoxin is not sufficient to control atrial fibrillation, the addition of a beta-adrenergic blocking agent is recommended as adjunctive treatment in selected patients.