In a two-year randomized controlled study, we studied the effects of bronchodilator treatment on the lung function and the quality of life in patients with mild airflow obstruction. The patients were randomly divided to receive either continuous or symptomatic bronchodilator treatment. Within these treatment groups, they received salbutamol in the first year and ipratropium bromide in the second or vice versa. In addition, the quality of life of the patients was compared to that of the general population. One hundred and forty-four patients completed the study. When compared to the general population, these patients showed a serious impairment in quality of life. No differences between the two drugs were found, but the results indicated that FEV1 decline in the continuously treated group was significantly larger than in the symptomatically treated group. However, this was not reflected in a significant deterioration of the quality of life in the continuous group as measured by means of the Nottingham Health Profile and the Inventory of Subjective Health. Decline in FEV1 showed no correlation with changes in quality of life scores. This may be due to a relatively rapid adjustment of the patients to a decline in FEV1, as a result of which it has no direct effect on the experienced quality of life. Another reason may be that continuous bronchodilation masks the worsening of the disease. This lack of awareness might in turn be caused by the continuous symptom relief of bronchodilators.

To demonstrate the utility of pulse oximetry in detecting clinically unapparent episodes of arterial desaturation in postoperative cardiac surgical patients and to evaluate the effect of pulse oximetry on ordering arterial blood gas analyses.

In patients with asthma, the respiratory muscles have to overcome the increased resistance while they become progressively disadvantaged by hyperinflation. We hypothesized that increasing respiratory muscle strength and endurance with specific inspiratory muscle training (SIMT) would result in improvement in asthma symptoms in patients with asthma. Thirty patients with moderate to severe asthma were recruited into 2 groups; 15 patients received SIMT (group A) and 15 patients were assigned to the control group (group B) and got sham training in a double-blind group-comparative trial. The training was performed using a threshold inspiratory muscle trainer. Subjects of both groups trained five times a week, each session consisted of 1/2-h training, for six months. Inspiratory muscle strength, as expressed by the PImax at RV, increased significantly, from 84.0 +/- 4.3 to 107.0 +/- 4.8 cm H2O (p < 0.0001) and the respiratory muscle endurance, as expressed by the relationship between Pmpeak and PImax from 67.5 +/- 3.1 percent to 93.1 +/- 1.2 percent (p < 0.0001), in patients of group A, but not in patients of group B. This improvement was associated with significant improvements compared with baseline for asthma symptoms (nighttime asthma, p < 0.05; morning tightness, p < 0.05; daytime asthma, p < 0.01; cough, p < 0.005), inhaled B2 usage (p < 0.05), and the number of hospital (p < 0.05) and sick-leave (p < 0.05) days due to asthma. Five patients were able to stop taking oral/IM corticosteroids while on training and one in the placebo group. We conclude that SIMT, for six months, improves the inspiratory muscle strength and endurance, and results in improvement in asthma symptoms, hospitalizations for asthma, emergency department contact, absence from school or work, and medication consumption in patients with asthma.

We compared, in a controlled clinical trial, the effect of specific inspiratory muscle training combined with general exercise reconditioning, for six months, with that of general exercise reconditioning alone on inspiratory muscle strength, endurance, and exercise performance in patients with COPD. Thirty-six patients were recruited into three groups; 12 patients received specific inspiratory muscle training combined with general exercise reconditioning, 12 patients underwent general exercise reconditioning alone, and the remaining 12 patients received no training. Specific inspiratory muscle training, for six months, improved the inspiratory muscle strength and endurance in patients with COPD. This training combined with general exercise reconditioning also provided improvement in exercise tolerance, and this improvement was significantly greater than that of general exercise reconditioning alone.

To compare the thermal and humidification capacity of three heated hot water systems (HHWSs) and two heat and moisture exchangers (HMEs) in ICU patients submitted to minute ventilation > 10 L/min.

The usefulness of the intravenous dipyridamole-echocardiography test (12-lead and two-dimensional [2-D] echo monitoring during dipyridamole infusion) in the diagnosis of coronary artery disease recently has been suggested. However, the intravenous form of dipyridamole is not available for clinical use in some countries and therefore the administration of oral dipyridamole has been employed in combination with echocardiography. In order to evaluate the relative usefulness of the oral (300 mg of pulverized tablets) vs the intravenous (up to 0.84 mg/kg in 10 min) dipyridamole-echocardiography test, we performed the two tests, on different days and in random order, in 28 inhospital patients: 21 had coronary artery disease (seven had one-vessel disease, eight had two-vessel disease, and six had three-vessel disease); seven patients had no significant coronary artery disease. For both tests, the diagnostic end-point was the development of a transient dyssynergy of contraction. Sensitivity was 95 percent for the intravenous and 52 percent for the oral dipyridamole-echocardiography test (p < 0.01); in positive cases, the dyssynergy after the dipyridamole administration appeared at 6.5 +/- 2.5 min for the intravenous and at 27.8 +/- 12.4 min for the oral test (p < 0.01). Specificity was 100 percent for both the intravenous and oral dipyridamole-echocardiography test. One or more extracardiac side effects (headache, gastrointestinal upset, flushing, etc) occurred in 61 percent of the intravenous and 68 percent of the oral tests (p = ns). Nine patients with a positive intravenous and oral dipyridamole-echocardiography test also had a positive exercise-electrocardiography test. A significant correlation between exercise time (ie, the time from onset of exercise and 0.1 m V of ST segment shift) and dipyridamole time (ie, the time from onset of dipyridamole administration and the development of frank dyssynergy) was present for the intravenous (r = 0.6, p < 0.05) but not for the oral test. We conclude that the oral dipyridamole-echocardiography test, in comparison with the intravenous dipyridamole-echocardiography test, has a lower sensitivity and requires a substantially longer imaging time. The dipyridamole time is related to exercise time for intravenous but not for the oral dipyridamole-echocardiography test.

Within hours, tolerance occurs to repeated methacholine challenge in normal subjects, and this study examines whether prostaglandin synthesis produces this phenomenon. On two separate study days, ten nonasthmatic non-smoking subjects with measurable baseline responsiveness to methacholine performed five sequential methacholine challenge tests over 6 h. Pretreatment before each day consisted of either placebo tablets or 50-mg tablets of indomethacin given three times daily for 48 h prior to testing. Medications were administered in a single-blind crossover fashion, with study days assigned in random order and separated by at least 1 wk. Methacholine challenge tests were summarized by the PD20FEV1 (the provocative dose in cumulative breath units [cbu] required to produce a 20 percent fall in FEV1). Indomethacin pretreatment had no effect on baseline spirometry between the two study days; however, the baseline geometric mean PD20FEV1 fell from 145 +/- 2 cbu (+/- percent SD) after placebo pretreatment to 65 +/- 1 cbu (+/- percent SD) on the indomethacin day (p = 0.046). This effect of indomethacin on baseline airway responsiveness persisted when an additional ten subjects were studied to further investigate this finding. Significant tolerance to repeated methacholine challenges occurred on both study days, with geometric mean PD20FEV1 rising approximately 16-fold (p less than 0.0001) regardless of pretreatment received. This study demonstrates that the attenuation of methacholine's effect with repeated testing is not due solely to prostaglandin synthesis and must involve, in part, other mechanisms, such as changes in methacholine deposition, agonist-receptor interactions, or postreceptor responses. In addition, prostaglandin inhibitors may increase baseline methacholine responsiveness in healthy nonasthmatic subjects.

Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure.

A patient's tolerance of fiberoptic bronchoscopy depends on the effectiveness of local anesthesia. This study compares the three different methods of local anesthesia in common use After sedation, patients (n = 53) received either 4 ml of 2.5 percent cocaine by intratracheal injection (TI) (n = 18), by bronchoscopic injection (BI) (n = 19), or had 4 ml of 4 percent lidocaine delivered by nebulizer 20 min before the procedure (NEB) (n = 16). Patients and bronchoscopists scored the procedure using visual analog (VAS) and severity scales. Objective measurements of cough counts and episodes of stridor were recorded by phonopneumography. Patients' VAS scores showed a clear preference for the transtracheal method compared with either bronchoscopically injected cocaine (p less than 0.001) or nebulized lidocaine (p less than 0.001). Patients also reported that the TI method produced less cough during intubation of the larynx and inspection of the airways (BI and NEB, p less than 0.01). The TI method was also preferred by the bronchoscopists (BI and NEB, p less than 0.001); they reported less cough and easier tracheal intubation. The mean cough count was significantly lower for the TI group, 49 (43) compared with 95 (52) for BI (p less than 0.01), and 81 (43) for the NEB group (p less than 0.05). Patients' and bronchoscopists' VAS showed significant correlation with cough (r = 0.63-69, p less than 0.01). Stridor occurred in only two patients after TI, compared with 15 in the other two groups. Extra local anesthesia was required by 16 patients after BI, by all the NEB group, but by only one patient after TI. Subjective and objective measurement shows that 4 ml of 2.5 percent cocaine injected into the trachea produced excellent local anesthesia for fiberoptic bronchoscopy, there were no extra complications, and it was the method preferred by both patients and bronchoscopists.

In a recent study, it was suggested that the preservatives in ipratropium bromide nebulizer solution may cause a paradoxic bronchoconstrictor response in 20 percent or more of patients with stable asthma. The frequency of this response in patients with acute asthma is unknown. The aim of this study was to examine the acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in patients with either stable or acute asthma using formulations with and without added preservatives. Twenty-five patients with stable asthma and 25 patients with acute asthma were studied. Each subject was given preservative-containing ipratropium bromide, preservative-free ipratropium bromide, pH 7 preservative-free ipratropium bromide, and saline solution in random order using a double-blind crossover technique with at least 4 h between drug administrations. Very frequent measurements of FEV1 were made for 30 min after each drug administration and then 5 mg of albuterol was nebulized and the FEV1 was measured again after another 30 min. Changes in FEV1 were expressed as a percentage of the predicted FEV1. Paradoxic bronchoconstriction to ipratropium was detected in only one patient with acute asthma (12 percent fall in FEV1) but in none of the patients with stable asthma. A 6 percent fall in FEV1 change occurred with the saline solution in this subject suggesting that the response may have been a nonspecific one due to increased bronchial responsiveness. The mean response (+/- 1 SD) to albuterol plus either preservative-containing ipratropium, preservative-free ipratropium, or pH7 preservative-free ipratropium was significantly greater (p less than 0.05) than the response to albuterol alone both in the patients with acute asthma (25 +/- 12 percent, 27 +/- 15 percent, 26 +/- 15 percent, and 20 +/- 15 percent, respectively) and stable asthma (26 +/- 7 percent, 25 +/- 8 percent, 24 +/- 6 percent, and 22 +/- 9 percent) supporting the use of ipratropium bromide as an additional bronchodilator in patients with asthma who do not show a satisfactory response to nebulized beta-adrenergic agonist.

Chronic hypoxemia is associated with development of secondary polycythemia. To evaluate effects of transient hypoxemia on serum EPO activity in patients with chronic lung disease, we studied six oxygen-dependent patients who underwent either a 4-h oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on two separate days. Serum EPO did not differ at baseline between study days. Erythropoietin levels did not change significantly over time during normoxic conditions. Under hypoxic conditions, serum EPO levels rose over 4 h with the change from baseline first becoming significant at 2 h. The log of serum EPO response showed an inverse correlation with the level of arterial oxygen saturation. We conclude that patients with chronic lung disease are able to produce EPO in response to acute hypoxemic stress. Transient episodes of hypoxemia, such as occur during sleep or exercise, may result in increased red blood cell production stimulated by this EPO response.

The treatment of nocturnal asthma remains a challenge. We investigated the use of a pulsed-released albuterol in ten patients with nocturnal symptoms of asthma. In a randomized, double-blind, placebo-controlled, crossover designed study, we tested the use of 8 mg of pulsed-release albuterol sulfate (Proventil Repetabs) vs placebo. The pulsed-release albuterol significantly blunted the overnight drop in FEV1, improved peak flow readings in the morning, and decreased subjective awakenings from sleep. We conclude that pulsed-released albuterol is an effective therapeutic option in patients with nocturnal asthma.

The thresholds used to define a positive result for bronchial provocation challenges (BPC) are arbitrary. Requiring smaller decrements in expired flow to define a positive study would capture more cases of reactive airways (increased sensitivity) but would include some "normal" responses (decreased specificity). To examine the relationship between threshold definition and the ability to correctly classify subjects as either normal or as having airways hyperresponsiveness (AHR), four different BPC tests were administered on different days to 20 patients with a clinical diagnosis of exercise-induced bronchospasm (EIB) and 20 control subjects. The four BPC tests were indoor exercise on a cycle ergometer, methacholine inhalation challenge (MIC), eucapnic voluntary hyperventilation (EVH) with dry gas, and EVH with cold gas. Our results indicate that the thresholds which best separate the two groups are different for each of the four BPC techniques. For methacholine inhalation (MIC), a fall in FEV1 (d%FEV1) of 15 percent or greater at 188 cumulative breath units was 100 percent specific for AHR but had a sensitivity of only 55 percent. Eucapnic voluntary hyperventilation (EVH) with room temperature dry gas was 100 percent specific at a d%FEV1 of 11 percent, but, at that threshold, sensitivity was only 50 percent. EVH with cold air was 100 percent specific at a d%FEV1 of 12 percent but sensitivity was only 35 percent. The bicycle ergometer challenge was far too insensitive to be of value in evaluating AHR. Based on their respective receiver operating characteristic curves, the best separation of the two subject groups occurred at a d%FEV1 of 5 percent and 12 percent for the two EVH techniques and MIC, respectively. An individual's response to one test was highly correlated with the response to either of the other two (r = 0.66, p less than 0.001 for dry vs cold gas EVH; r = 0.56, p less than 0.001 for dry gas EVH vs methacholine; and r = 0.69, p less than 0.001 for cold gas EVH vs methacholine). Thus, MIC and EVH techniques are equally useful in defining AHR and each has its optimal threshold for a positive test result.

Twelve patients with stable asthma (mean age, 39 years; asthma duration, 11 years; mean forced expiratory volume in 1 s, 65 percent of predicted; and reversibility, 31 percent) were studied in a double-blind crossover trial. The patients were studied during three test days. Airway resistance and specific airway conductance (Raw and SGaw) were measured using a body plethysmograph and pulse rate, blood pressure, tremor, and subjective effects were recorded before and 1, 3, 5, 10, 15, 30, 60, and 120 min after the test doses. A baseline Raw variability of +/- 20 percent was allowed between the test days. Formoterol 12 micrograms, 24 micrograms, and terbutaline 500 micrograms were given in a spacer (Nebulator) in a randomized double-blind crossover manner as two puffs with a 30-s interval in between. The effect of formoterol 12 micrograms on Raw was significantly better than terbutaline after 3, 5, 10, 60, and 120 min. Formoterol 24 micrograms was significantly better than terbutaline as soon as 3 min after inhalation and at every point in time after that. Formoterol 24 micrograms tended to be better than formoterol 12 micrograms but the differences were not significant at any point in time. All three treatments were well-tolerated. No differences were observed for pulse rate, blood pressure, tremor, or palpitations. The overall onset of bronchodilatation after formoterol 12 and 24 micrograms was faster than after terbutaline 500 micrograms. The tolerability of formoterol was good.

The aim of this study was to investigate whether the administration of prednisone potentiates any of the acute biochemical and cardiovascular effects of high-dose inhaled beta-agonist drugs. These agents are known to cause dose-related changes in plasma potassium and glucose, as well as ECG changes in heart rate, corrected QT interval (QTc), T wave, and U wave. On theoretical grounds, the concomitant use of systemic corticosteroids might enhance these actions. Twenty-four healthy subjects were randomized to receive one of three treatments: salbutamol 5 mg or fenoterol 5 mg or normal saline solution. Each drug was administered twice, 30 min apart by nebulizer, and the procedure was repeated after each subject had received prednisone 30 mg daily for one week. Plasma potassium and glucose levels were measured, and ECGs were obtained after each treatment, together with 12-h Holter monitoring for arrhythmias. Changes in plasma potassium and glucose following nebulized beta-agonist were significantly greater after treatment with prednisone. Baseline potassium level fell from 3.75 mmol/L (95 percent CI 3.61, 3.89) to 3.50 mmol/L (95 percent CI 3.36, 3.64), and thereafter all values were significantly lower at each time point (p = 0.003). The lowest mean plasma potassium was obtained 90 min after fenoterol administration with prednisone pretreatment: 2.78 mmol/L (95 percent CI 2.44, 3.13). Increases in heart rate and QTc interval following both beta-agonist drugs were significant, but T-wave amplitude reductions did not reach significance. Prednisone treatment did not significantly alter the cardiovascular responses. Supraventricular and ventricular ectopic activity was related to beta-agonist use, but no potentiating effect was noted following steroid treatment. We conclude that the acute biochemical effects of beta-agonist administration are augmented by prior treatment with prednisone, but this is not the case for ECG effects. However, the degree of hypokalemia noted as a result of this drug interaction may be of clinical significance in the hypoxic conditions of acute airways obstruction.

To investigate whether enalapril (E) 10 mg and spironolactone (S) 100 mg attenuate the hypokalemic effect of inhaled terbutaline (T).

Septic shock is characterized by hypoperfusion and tissue energy defects. We prospectively evaluated the therapeutic benefit of augmenting cardiac output and therefore oxygen delivery (DO2) on mortality in patients with septic shock. Twenty-five patients were randomized to a normal treatment (NT) group and 26 patients were randomized to an optimal treatment (OT) group. All patients had a clinically evident site of infection, sepsis as defined by a systemic response to the infection, and shock indicated by systemic hypoperfusion. Patients were treated during the initial 72 h by an algorithm differing only in the end point of resuscitation. The cardiac index (CI) was increased to 3.0 L/min/m2 in the NT group and to 6 L/min/m2 in the OT group. There were no significant differences in cardiorespiratory parameters in the NT and OT groups on entrance into the study. During treatment, CI averaged 3.6 +/- 0.2 L/min/m2 and DO2 averaged 8.6 +/- 0.8 ml/min/kg in the NT group and CI averaged 5.1 +/- 0.2 L/min/m2 and DO2 averaged 12.2 +/- 0.7 ml/min/kg in the OT group (p less than 0.01). A significant correlation between DO2 and survival was observed. Seventy-two percent of the OT patients died vs 50 percent of the NT patients (p = 0.14). Surviving NT patients stayed 13.7 +/- 3 days in the ICU vs 7.4 +/- 0.6 days (p less than 0.05) for the OT patients. Since some of the NT patients were spontaneously hyperdynamic and some of the OT patients did not achieve their desired end point, patients were arbitrarily subsetted using a midpoint CI of 4.5 L/min/m2. The NT less than 4.5 group had a CI of 3.1 +/- 0.2 L/min/m2 and DO2 of 10.9 +/- 1.0 ml/min/kg while the OT group greater than 4.5 L/min/m2 had a CI of 5.7 +/- 0.2 L/min/m2 and a DO2 of 13.8 +/- 0.7 ml/min/kg (p less than 0.01). Mortality in the NT less than 4.5 group was 74 percent as compared with 40 percent in the OT greater than 4.5 group (p less than 0.05).

In a series of 253 high-risk surgical patients, we measured the oxygen consumption (VO2) at frequent intervals before, during, and immediately after surgical operations and calculated the rate of VO2 deficit from the measured VO2 minus the VO2 need estimated from the patient's own resting preoperative control values corrected for both temperature and anesthesia. The calculated oxygen deficit was related to multiple organ failure, complications, and outcome. The 64 patients who died all had organ failure; their cumulative VO2 deficit averaged 33.2 +/- 4.0 L/m2 (+/- SEM) at its maximum, which occurred 17.8 +/- 2.2 h after surgery. In the 31 survivors with organ failure, the cumulative VO2 deficit averaged 21.6 +/- 3.7 L/m2 at its maximum, which occurred 10.1 +/- 2.7 h after surgery (p less than 0.05). In the 158 survivors without organ failure or major complications, the maximum cumulative VO2 deficit averaged 9.2 +/- 1.3 L/m2 at 4.1 +/- 0.6 h after surgery (p less than 0.05). In a prospective randomized clinical trial, a protocol group maintained at supranormal hemodynamic and oxygen transport values had significantly reduced oxygen debt (7.6 +/- 3.4 L/m2 vs 17.3 +/- 6.8 L/m2; p less than 0.05), fewer organ failures, and lower mortality (4 percent vs 33 percent; p less than 0.05) compared with a control group maintained at normal hemodynamic values. The data demonstrate a strong relationship between the magnitude and duration of the VO2 deficit in the intraoperative and early postoperative period and the subsequent appearance of organ failure and death. The latter may be reduced when oxygen debts were prevented or minimized by augmenting naturally occurring compensations that increased oxygen delivery.

To investigate the effect of nedocromil sodium on changes in airway reactivity to methacholine induced by platelet activating factor, we studied 12 nonasthmatic, nonatopic subjects (24 to 41 years) in a double-blind trial. The FEV1 and airflow at 30 percent of vital capacity from a partial forced expiration (V30p) were used to assess changes in airway caliber. Two concentration-response curves to doubling concentrations of MCh (from 0.3 mg/ml) were performed 48 h apart. The concentrations of MCh causing a 20 percent fall in FEV1 (PC20FEV1) or a 40 percent fall in V30p (PC40V30p) were calculated. After the first MCh challenge, subjects were matched by airway reactivity and randomly assigned to nedocromil sodium (two puffs qid 2 mg/puff) or placebo treatment. Two days after the second MCh challenge, PAF was inhaled, and changes in airway caliber were recorded. Administration of either nedocromil sodium or placebo was ended at this time and airway response to MCh was assessed two days after PAF. The two concentration-response curves to MCh obtained before PAF exposure were superimposable. The PAF caused a dose-related bronchoconstriction in both groups; the maximal fall in V30p was 27.6 +/- 6.6 percent (mean +/- SE) in the nedocromil sodium group and 37.4 +/- 4.6 percent in the placebo group. Two days after PAF, the PC20FEV1 did not change in subjects who received nedocromil sodium (4.86 vs 4.32 mg/ml; geometric mean), but it fell from 6.59 to 1.12 mg/ml (p less than 0.05) in placebo-treated subjects. These results indicate that nedocromil sodium inhibits PAF-induced increase in airway reactivity.

In untreated patients with uncomplicated essential hypertension, exercise induces an abnormal increase in blood pressure; the influences of this increase on exercise were evaluated by a cardiopulmonary exercise test (CPX) performed in control conditions (step 1) and during acute blood pressure reduction (step 2). Patients were classified as (1) normotensive (resting diastolic blood pressure [BPd] less than 90 mm Hg; n = 14), (2) mildly hypertensive (BPd of 90 to 104 mm Hg; n = 9), and (3) moderately to severely hypertensive (BPd greater than or equal to 105 mm Hg; n = 16). For the three groups, peak mean blood pressure during exercise was 125 +/- 5 mm Hg (mean +/- SEM), 144 +/- 3 mm Hg (p less than 0.01 vs normotensive), and 161 +/- 4 mm Hg (p less than 0.01 vs normotensive and p less than 0.01 vs mild hypertension), respectively. Oxygen consumption (VO2) at peak exercise and at ventilatory anaerobic threshold was 26.1 +/- 1.1 and 17.2 +/- 0.5 ml/min/kg, 25.4 +/- 1.1 and 16.9 +/- 0.8 ml/min/kg, and 26.4 +/- 1.3 and 17.5 +/- 1.2 ml/min/kg in normotensive subjects, those with mild hypertension, and those with moderate to severe hypertension, respectively. Fourteen normotensive subjects, six with mild hypertension, and nine with moderate to severe hypertension participated to step 2 (nifedipine vs placebo, double-blind crossover). Nifedipine reduced blood pressure at rest and at peak exercise in those with hypertension. Peak exercise VO2 was unaffected by nifedipine in both normotensive subjects and those with hypertension. With nifedipine, ventilatory anaerobic threshold occurred earlier and at a lower VO2 in mild and in moderate to severe hypertension (delta VO2 = -1.9 and -2.4 ml/min/kg, respectively). These findings might be due to nifedipine-induced redistribution of blood flow during exercise and might be the reason for the complaint of weakness after blood pressure reduction in hypertensive subjects.