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Seven male patients with hypercapnic chronic bronchitis were given the ventilatory stimulant drug medroxyprogesterone acetate (MPA) 20 mg t.d.s. orally for 4 weeks preceded by a control period of one week. The patients were assessed at the beginning and end of the control period, at 2-weekly intervals while they took the drug and 2 weeks to 5 months after they stopped it. Arterial blood gases, spirometry and a 12-minute walking test were performed on each occasion. During treatment with MPA, arterial Pco2 fell in all patients from a mean control of 50.6 (+/- 1 SEM) mmHg to 44.4 (+/- 1) mmHg (P less than 0.001) and Po2 rose in all patients from a mean control of 53 (+/- 1.9) mmHg to 61 (+/- 3.2) mmHg (P less than 0.05). These effects were achieved without changes in PEFR, FEV1 or FVC. In spite of this, there was no improvement in the sensation of dyspnoea on visual analogue scales at rest or after exercise, and no significant increase in the 12-minute walking distance. The only side effect associated with MPA was slight fluid retention. Ventilatory stimulation with MPA improves arterial blood gases in hypercapnic chronic bronchitis but there is no accompanying improvement in symptoms or exercise tolerance.
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PMID:The effect of ventilatory stimulation with medroxyprogesterone on exercise performance and the sensation of dyspnoea in hypercapnic chronic bronchitis. 379 Apr 18

Invasive studies in patients with left ventricular dysfunction show that data at rest (e.g. ejection fraction-EF) are poor predictors of the changes in cardiac output (CO) which occur with exercise. This investigation was undertaken to determine whether impedance cardiography could be used in such patients to assess CO response to exercise. The method was compared with the direct Fick method. Over a range of COs between 4 and 18 min-1 there was no systematic error. Reproducibility for CO over one week was highly significant (r = 0.94; P less than 0.001). Impedance cardiography was incorporated into routine exercise testing on a bicycle ergometer for a group of 15 patients (mean age 53.2 +/- 3.0 yrs, SEM) who had sustained a major myocardial infarct 6 to 12 months previously, (EF 38.1 +/- 3.5%, SEM). CO was measured at the end of each 3-min stage. In eight patients (EF 40.0 +/- 3.4%, SEM) CO response was abnormal with either a decrease or a failure to increase with increasing workloads. Conventional end-points i.e. angina, attainment of 85% of predicted maximum heart rate, abnormal blood pressure response or excessive dyspnoea did not indicate consistently a need to terminate the test. It is suggested that impedance cardiography is a useful non-invasive method of evaluating patients with left ventricular dysfunction.
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PMID:Use of impedance cardiography in evaluating the exercise response of patients with left ventricular dysfunction. 383 Jul 7

Stimulated by a patient with dyspnea, thrombocytopenia, and leukopenia after sodium morrhuate sclerotherapy, we studied the effect of this agent on the plasma coagulation and complement systems, the formed elements of the blood, and cultured human endothelial cells. The addition of sodium morrhuate to citrated plasma did not cause clotting or shorten the prothrombin time or partial thromboplastin time. Incubation of a 1:100 dilution of the clinical sodium morrhuate preparation in heparinized plasma led to a modest rise in [C3a]. The addition of the drug (dilutions 1:50 to 1:300) to granulocytes caused prompt aggregation (and, at the higher concentrations, granulocyte cytotoxicity [trypan blue exclusion; lactate dehydrogenase release]), but the same dilutions failed to aggregate platelets. However, 0.05% morrhuate added to washed red blood cells caused a prompt 84.0% (+/- 0.8% SEM) hemolysis, rendering the supernatant buffer a potent platelet aggregant. Not only was this sclerosing agent toxic to granulocytes and red cells, but a 1:1000 dilution of the drug also caused the destruction of 35.5% (+/- 6.6%) of cultured endothelial cells as measured by chromium 51 release. Three other agents in current use (ethanolamine oleate, sodium tetradecyl sulfate, and polidocanol) were studied and found to cause effects qualitatively similar to those of sodium morrhuate. We conclude that these drugs cause phlebosclerosis not primarily through induction of plasma coagulation, but by directly damaging endothelium and red cells, triggering platelets, and aggregating granulocytes at the venous wall endothelium. These effects likely derive from the surfactant properties of sodium morrhuate as well as its high arachidonate content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sodium morrhuate stimulates granulocytes and damages erythrocytes and endothelial cells: probable mechanism of an adverse reaction during sclerotherapy. 405 66

Ten patients with severe dyspnoea and chronic airflow obstruction entered a randomised double-blind crossover trial comparing the effect of carbimazole 80 mg daily for two months with that of placebo. Assessment of thyroid function, lung function, and exercise tolerance was performed monthly. The mean free thyroxine index after two months of carbimazole was significantly lower at 64.1 (+/- 10.5, SEM) than the 89.1 (+/- 3.8) while on placebo. Serum tri-iodothyronine was reduced and thyroid stimulating hormone raised while on the active drug. There was no significant difference in the 12-minute walking distance (TMD), the rating of perceived exertion during the TMD, the oxygen cost score, the dyspnoea grade, the resting arterialised capillary blood gas tensions or the resting minute ventilation. During a progressive exercise test to exhaustion on a cycle ergometer, there was no significant difference in the minute ventilation, heart rate, blood gas tensions at exhaustion, or the total work done. There were no symptoms or signs of hypothyroidism. Lung function (FEV1, FVC, TLC, KCO) was unchanged. Thus a 28% reduction in the free thyroxine index produced no symptomatic or objective benefit in exercise tolerance in patients with severe airflow obstruction. These results provide no support for the use of carbimazole in chronic airflow obstruction.
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PMID:Carbimazole and exercise tolerance in chronic airflow obstruction. 704 24

About one-third of patients who have severe left ventricular dysfunction can achieve normal levels of exercise. To elucidate the mechanisms that permit this to occur, we studied six patients with severe left ventricular dysfunction (average left ventricular ejection fraction 17 +/- 2.5% [mean +/- SEM]) who achieved nearly normal levels of exercise tolerance (greater than 11 minutes of treadmill exercise, Sheffield protocol). All patients had normal pulmonary function at rest and during exercise. Hemodynamics were measured at rest and during supine and upright exercise. The major mechanisms of the preserved exercise capacity in these patients were chronotropic competence, ability to tolerate elevated wedge pressures (33 +/- 3 mm Hg) without dyspnea, ventricular dilation, and increased levels of plasma norepinephrine at rest and during exercise. Also, whereas peripheral vascular resistance was unchanged during supine exercise, it decreased by 50% during similar levels of upright exercise. As a consequence, increases in cardiac output from rest to exercise were greater during upright than supine exercise (100% vs 50%, respectively) (p less than 0.05), and pulmonary wedge pressures were lower during upright than supine exercise (21 +/- 5 mm Hg vs 33 +/- 3 mm Hg). Thus, multiple mechanisms permit some patients with severe left ventricular dysfunction to achieve normal levels of exercise. These studies emphasize that left ventricular function must be assessed by direct means rather than inferring function of the left ventricle from the results of an exercise tolerance test.
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PMID:Normal exercise capacity in patients with severe left ventricular dysfunction: compensatory mechanisms. 708 99

The effects of the inspiratory threshold load (ITL) on breathlessness and ventilatory mechanics during acute bronchoconstriction were studied by comparing responses to continuous positive airway pressure (CPAP) and inspiratory positive airway pressure (IPAP) in 12 asthmatic subjects after methacholine bronchoprovocation to a maximum change (delta) in FEV1 of 50%. At maximum response, "optimal CPAP" (CPAPOPT) was selected as the level of CPAP providing maximum subjective improvement in breathlessness. Spirometry, breathing pattern, esophageal pressure (Pes), and operational lung volumes were monitored. At maximum response, FEV1 decreased by 54 +/- 3% (mean +/- SEM) (p < 0.001), dynamic end-expiratory volume (EELVdyn) increased 66 +/- 8%, by 1.4 +/- 0.2 L (p < 0.001), and subjects reported severe breathlessness (Borg Scale = 5.6 +/- 0.8). CPAPOPT (5.3 +/- 0.6 cm H2O) significantly (p < 0.001) reduced breathlessness (delta Borg Scale = -3.0 +/- 0.5) and did not cause further dynamic hyperinflation. CPAPOPT reduced peak inspiratory Pes by 27% (p < 0.001), the tension-time index (TTI) for the inspiratory muscles by 27% (p < 0.01), and the inspiratory work rate per liter of ventilation by 14% (p < 0.05). During CPAPOPT, the delivered extrinsic positive end-expiratory pressure (PEEPe) (6.4 +/- 0.4 cm H2O) was strongly related (p < 0.001) to the measured ITL (6.9 +/- 1.0 cm H2O) at maximum response. Responses to IPAP of the same magnitude as CPAP OPT at maximum response were similar to those during CPAPOPT, except that IPAP did not counteract ITL or reduce breathlessness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Breathlessness during induced lung hyperinflation in asthma: the role of the inspiratory threshold load. 766 4

Exercise training has been of limited success in patients with severe chronic airflow obstruction (CAO), in part because of the reduced ventilatory capacity and excessive dyspnea experienced. Pressure support (PS) is a new form of mechanical ventilation which can effectively assist ventilation when applied noninvasively to patients in acute respiratory failure. It was hypothesized that PS might also be used to improve exercise performance, and ultimately physical conditioning, in ambulatory patients with CAO undergoing exercise training. To begin to address this concept, the objectives of the present study were (1) to examine the feasibility of providing PS to exercising patients with CAO and (2) to determine its effects on breathing pattern, inspiratory effort, and dyspnea. Flow and volume, mouth, esophageal, and gastric pressure were measured in seven patients with severe CAO (mean FEV1 = 0.75 +/- SEM 0.09 L) performing constant workload bicycle exercise (33 +/- 6 watts) during control conditions and with the application of PS (approximately 10 cm H2O). PS increased minute ventilation as a result of changes in both tidal volume and respiratory rate. This occurred despite marked reductions in inspiratory effort, as indicated by the pressure-time integrals of esophageal (68 +/- 5% control, p < 0.0005) and transdiaphragmatic pressure (52 +/- 8% control, p < 0.0005). Using a 5-point bidirectional scale to assess changes in dyspnea, breathlessness improved significantly with the addition of PS (2.3 +/- 0.6, p < 0.05) and worsened to a similar degree when it was removed (2.1 +/- 0.5, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pressure support reduces inspiratory effort and dyspnea during exercise in chronic airflow obstruction. 769 26

Recent objective studies demonstrate relatively low hours of nightly use during nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). Patients frequently complain of dyspnea or discomfort during CPAP use, especially during expiration (against the continuous pressure), which may be a reason for the low hours of use. We hypothesized that with decreased expiratory pressure, hours of nightly use would increase. Therefore, we randomized 83 OSA patients to receive either continuous or bilevel positive airway pressure when expiratory pressure is lower. To document objectively the effective use of either therapy, we built and installed elapsed-time and mask pressure sensors in the patients' positive airway pressure units. A total of 62 patients were evaluable and followed for 1 yr. Of these, 26 received bilevel and 36 CPAP pressures. The machine timers measured accumulated "machine-on" time, and the mask pressure sensor recorded the total time in which the mask pressure was within 2 cm H2O of the effective pressure (pressure shown to eliminate 95% of the obstructive apneas during a full night of polysomnography). The mean machine timer hours of CPAP were 5.0 +/- 0.19 SEM and 4.9 +/- 0.23 SEM during bilevel therapy (p NS) over a 12-mo period. The pressures required during CPAP or bilevel therapy were not different between high and low hourly users. Effective use, the percentage of time that the machine was running and the prescribed pressure was being delivered, was 80% in CPAP and 82% in the bilevel users (p NS). Both groups had equal complaints with regard to mask discomfort, machine noise, and nasal stuffiness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous versus bilevel positive airway pressure for obstructive sleep apnea. 784 4

The usefulness of inspiratory muscle training (IMT) in chronic airflow limitation (CAL) patients is a controversial issue, mainly due to differences in the training load. To further evaluate this aspect, we studied the effect of the magnitude of the load using a threshold pressure trainer. Ten CAL patients (5 males, 5 females) 67 +/- 2 yrs (mean +/- SEM) and forced expiratory volume in one second (FEV1) 36 +/- 2% pred, were trained for 30 min a day using a load of 30% of their maximal inspiratory mouth pressure (PImax) (Group 1). Another 10 CAL patients (5 males, 5 females), 73 +/- 2 yrs and FEV1 37 +/- 2% pred), were trained using only 12% of their PImax (Group 2). Training was assessed by PImax, inspiratory muscle power output (IMPO), sustainable inspiratory pressure (SIP), maximal inspiratory flow rate (VImax), pattern of breathing during loaded breathing, Mahler's dyspnoea score, and the 6 min walking distance (6MWD). After 5 weeks of training, Group 1 exhibited significant increments in: PImax (34 +/- 11%); IMPO (92 +/- 16%); SIP (36 +/- 9%); and VImax (34 +/- 13%). Dyspnoea was also reduced, and the 6MWD increased by 48 +/- 22 m. We observed no significant changes in Group 2. During loaded breathing, Group 1 showed a significant increment in tidal volume (VT) and mean inspiratory flow (VT/TI), and a reduction in inspiratory time (TI). In Group 2, VT and VT/TI also increased significantly, but the breathing frequency increased with a reduction of expiratory time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inspiratory muscle training in chronic airflow limitation: comparison of two different training loads with a threshold device. 792 5

The effect of breathing with a positive expiratory pressure of 5 cm H2O was investigated in eight patients with COPD (mean [SD]FEV1 = 54 [13] percent predicted). Specific work of breathing (Wsp) and myoelectrical activity of the following respiratory muscles were measured at rest: scalene muscle, parasternal muscle, and abdominal muscles. Minute ventilation (VE), end-tidal CO2 (FETCO2), physiologic dead space ventilation (VD/VT), oxygen uptake (VO2), and carbon dioxide output (VCO2) were measured at rest and during an incremental bicycle exercise test. Dyspnea sensation during exercise was quantified using the CR10 Borg-scale. All measurements were performed with and without positive expiratory pressure (PEP). During PEP breathing at rest mean (SEM) Wsp increased from 0.54 (0.13) J/L to 1.08 (0.10) J/L. The SEM VE decreased from 12.4 (1.0) L/min to 10.5 (1.1) L/min, and SEM VD/VT decreased from 0.39 (0.03) to 0.34 (0.03). There was a tendency for an increased phasic respiratory muscle activity during PEP breathing of all three muscles as compared with undisturbed breathing, but the changes were not statistically significant. During the exercise test with PEP, VE, VD/VT, VO2, and VCO2 were significantly lower, and FETCO2 was significantly higher as compared with the values obtained during the exercise test with undisturbed breathing. Dyspnea sensation during the exercise test with PEP, however, was higher than during the test with undisturbed breathing. The PEP breathing at rest may be useful in patients with COPD as it increases the efficiency of ventilation by reducing dead space ventilation. This beneficial effect also occurs during exercise, but here it is accompanied by increased dyspnea sensation.
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PMID:Effects of positive expiratory pressure breathing during exercise in patients with COPD. 813 41


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