Normal pulmonary circulation pressure values in healthy subjects at rest and during exercise

The paper is based on the results of an earlier retrospective international WHO study of normal pressure values in the pulmonary circulation and the right heart in 468 healthy individuals. The results of this study suggest that the pulmonary hypertension should be defined by the mean pulmonary artery pressure at rest of > or = 20 mmHg and not > or = 25 mmHg. Pulmonary wedge pressure should be < 12 mmHg. These results have recently been confirmed by the so far largest retrospective international study of normal values published by Kovacs et al and involving 1187 healthy volunteers. However, this study does not include pulmonary wedge pressure values. Normal values ofthe mean pulmonary artery pressure during exercise are determined by age. In healthy individuals younger than 50 years of age, the mean pulmonary artery pressure during exercise increases in parallel with increasing cardiac output. However, the increase in the mean pulmonary artery pressure during exercise is steeper in healthy individuals aged 50 years and over. This results from a sharper increase in the pulmonary wedge pressure caused probably by diastolic dysfunction of the left ventricle in the older population.     

Alpha-adrenergic control of skeletal muscle circulation at rest and during exercise in aging humans

Aging is associated with many changes in autonomic nervous system function that often lead to impairments in the normal ability to respond to physiological stressors commonly encountered in daily life. In addition, many of these chronic age-related changes in autonomic-circulatory function can potentially predispose the older adult to elevated risk for acute and chronic cardiovascular complications. One of the most pronounced and repeatable findings with respect to changes in the autonomic nervous system with human aging is the progressive increase in basal muscle sympathetic nerve activity (MSNA) directed to skeletal muscle vascular beds. Although the mechanism(s) underlying this sustained age-associated increase in MSNA are not completely understood, several changes in sympathetic a-adrenergic function occur with age. In this review, the authors discuss how aging affects (1) a-adrenergic control of skeletal muscle vascular tone under resting conditions and the differences that exist in this control of the upper and lower limbs (forearm vs leg circulation); (2) vasoconstrictor responsiveness to endogenous norepinephrine release, as well as the specific responsiveness of postjunctional a(1)- and a(2)-adrenergic receptors; and (3) sympathetic a-adrenergic control of muscle blood flow and vascular tone during exercise in humans. Further, they discuss how these changes in sympathetic a-adrenergic control of skeletal muscle blood vessels have important physiological and clinical implications for the aging human.     

Accuracy of two ear oximeters at rest and during exercise in pulmonary patients

The accuracy of 2 ear oximeters (Hewlett-Packard 47201A and Biox IIA) was evaluated at rest and during exercise in 116 pulmonary patients. Ear oximetry measurements were compared with arterial oxygen saturation (SaO2) measured from simultaneous arterial blood samples. When used according to the manufacturer's instructions for stabilization during exercise testing, both oximeters demonstrated comparable accuracy in estimating arterial blood SaO2 both at rest and during exercise in these patients (95% confidence limits, 2 SEE = +/- 4 to 5%). The oximeters were more accurate in measuring a change in SaO2 from a previous reading (95% confidence limits, 2 SEE = +/- 2.5 to 3.5%). COHgb levels greater than 4% and dark skin pigmentation appeared to decrease the accuracy of ear oximetry measurements. Within the limitations of accuracy, both ear oximeters may be useful for clinical exercise testing in pulmonary patients.     

Hemodynamic effects of aerosolized iloprost in pulmonary hypertension at rest and during exercise

STUDY OBJECTIVES: Aerosolized iloprost, a stable prostacyclin analog, improves functional capacity even in patients with pulmonary hypertension who did not show a vigorous hemodynamic response after iloprost inhalation at rest. We therefore speculated that aerosolized iloprost elicits more beneficial effects on pulmonary hemodynamics during exercise than at rest. DESIGN AND SETTING: A prospective, open, uncontrolled study at a university hospital. PATIENTS: Sixteen patients with primary or secondary pulmonary hypertension. INTERVENTIONS: Right-heart catheterization at rest and during exercise before and after the inhalation iloprost, 14 to 28 microg. RESULTS: Before iloprost treatment, exercise increased mean (+/- SD) pulmonary artery pressure (PAPm) from 45 +/- 8 to 70 +/- 13 mm Hg, cardiac output from 3.7 +/- 1.0 to 5.8 +/- 2.4 L/min, and pulmonary vascular resistance (PVR) from 904 +/- 322 to 1,013 +/- 432 dyne.s.cm(-5) (each p < 0.05). After recovery, iloprost reduced PAPm from 44 +/- 8 to 41 +/- 6 mm Hg, increased cardiac output from 3.7 +/- 1.0 to 4.9 +/- 1.4 L/min, and lowered PVR from 902 +/- 350 to 636 +/- 248 dyne x s x cm(-5) (each p < 0.05). During exercise after iloprost, PAPm increased to 57 +/- 8 mm Hg, cardiac output to 7.0 +/- 3.0 L/min, and PVR to 673 +/- 279 dyne x s x cm(-5) (each p < 0.05 vs first exercise test). Systemic BP was not altered significantly by iloprost treatment during exercise. CONCLUSIONS: Aerosolized iloprost treatment exerts more favorable effects on pulmonary hemodynamics during exercise than at rest. These findings explain the functional improvement observed in patients with pulmonary hypertension who show only a moderate pulmonary vasodilatory response during iloprost inhalation at rest. Whether these beneficial effects have prognostic significance needs to be elucidated by further study.     

Hemodynamic effects of nifedipine at rest and during exercise in primary pulmonary hypertension

The potential short-term pulmonary vasodilator effect of a calcium-channel blocker, nifedipine, was tested in seven patients with primary pulmonary hypertension. Nifedipine (20 mg) produced a significant (p less than 0.01) and persistent decrease in mean pulmonary arterial pressure (58.1 +/- 14.3 to 48.6 +/- 16.3 mm Hg) and pulmonary vascular resistance (1,070 +/- 260 to 695 +/- 266 dynes X sec X cm-5). Cardiac index increased from 2.5 +/- 0.6 to 3.3 +/- 0.8 L/min/m2 (p less than 0.01), and heart rate was unchanged despite a fall in systemic pressure. In three patients tested during exercise on a bicycle, nifedipine resulted in an increase in the duration of exercise in two and a blunting of the exercise-induced increase in pulmonary pressure in all three. Long-term treatment was initiated in five of the seven patients and in two additional patients who did not receive nifedipine in the short-term study; all but one experienced symptomatic improvement. A persistent hemodynamic improvement was observed in three of the four patients restudied after long-term therapy. In conclusion, this study demonstrated the short-term beneficial hemodynamic effects of nifedipine, both at rest and during exercise. A more extensive long-term follow-up is necessary to establish the usefulness of this drug in the treatment of primary pulmonary hypertension.     

Influence of lung resection on pulmonary circulation and lung function at rest and on exercise.

Since June 1972, preoperative evaluation of the pulmonary hemodynamics and lung function tests at rest and on exercise were done in patients undergoing thoracotomy with lung resection. 49 patients have been investigated postoperatively, 28 patients had pre- and postoperative rightsided heart catheterization. 80% of the patients were feeling well and more than 50% were working again. The pulmonary hemodynamics showed postoperatively already at rest an increase of the pulmonary artery pressures, the cardiac index reached on exercise no longer the preoperative values and there was an increase of PCV pressures on exercise compared to preoperative. Stroke volume, heart rate, AV difference for oxygen, oxygen uptake, PaO2, V, VD/VT, AadO2, and diffusing capacity for CO steady state on exercise showed no statistical significant changes. The extent of lung resection showed no different influence on the pulmonary circulation for the time period investigated.     

Effect of sulfur dioxide on pulmonary macrophage endocytosis at rest and during exercise

Inhaled SO2 may cause damage by injuring upper airways. To what extent can SO2 also alter pulmonary macrophage function in the parenchyma and what is the impact of exercise? We studied the effect of SO2 on pulmonary macrophage endocytosis in resting and in exercising animals by measuring the rates of macrophage endocytosis in situ for 1 h of a test particle of insoluble radioactive colloidal gold (198Au), 1, 24, or 48 h after inhalation exposure to SO2. Resting hamsters exposed for 4 h to 50 ppm SO2 had no significant reduction in macrophage endocytosis compared with air-breathing control hamsters. However, if hamsters were exposed to the same concentration of SO2 while continuously running (40 min at 0.9 km/h), macrophage endocytosis was significantly reduced 1 h after exposure even though the exposure time was only one-sixth as long. Twenty-four hours later, the percentage of gold ingested by pulmonary macrophages remained significantly depressed. By 48 h, the rate had returned to control values. Exercise alone did not affect endocytosis. Hamsters exposed to 50 ppm SO2, with or without exercise, also showed significant reductions in the number of lavaged macrophages. This decrease was greatest and most persistent in the SO2 plus exercise group. These data indicate that even when animals are exposed to water-soluble gases, which are normally removed by the upper airways, exercise can potentiate damage to more peripheral components of the pulmonary defense system such as the macrophage.     

The pathogenesis of pulmonary and miliary tuberculosis

Tuberculosis is spread from human to human by airborne transmission; it is not a highly infectious disease. Primary infection remits in 90% of cases and is progressive in the remainder; it is accompanied by lymphohematogenous seeding of many organs, and reactivation may occur as early as three months or many years after initial infection. Primary infection generally confers immunity from subsequent reinfection. The risk of reactivation of tuberculosis is greatest in the year after infection, declining sharply thereafter for most patients. Acute miliary tuberculosis has a distinctive pathogenesis that is different from localized postprimary disease. Miliary tuberculosis may appear in a patient with a normal chest roentgenogram; even in patients with abnormal chest roentgenograms, sputum cultures for acid-fast organisms may be negative. Transbronchial biopsy is the preferred method of diagnosis and prompt initiation of treatment is essential.     

Equilibrium radionuclide right ventriculography at rest and during exercise in patients with pulmonary hypertension

Using the method of equilibrium radionuclide ventriculography (RNV), the right ventricular ejection fraction (RVEF) at rest and at a standard workload of 250 kpm per min was determined in 25 control subjects and in 30 patients with pulmonary hypertension (8 patients with chronic obstructive bronchopulmonary disease, 12 with recurrent pulmonary embolism and 10 with pure mitral stenosis). In the same week as RNV, pulmonary artery pressure was registered in patients with pulmonary hypertension at rest and at standard workload. RVEF was significantly higher (45 +/- 5%) in normal subjects than in patients with pulmonary hypertension (33 +/- 5%) and during exercise increased, whereas in patients with pulmonary hypertension it did not markedly change or decreased. The RVEF correlated at rest (r = -0.6293, p less than 0.001) and during exercise (r = 0.6980, p less than 0.05) with the degree of pulmonary hypertension at rest and during exercise. The results show a good correlation between the RVEF and the degree of pulmonary hypertension in patients with pulmonary hypertension at rest and during exercise.     

Determinants of pulmonary artery hypertension at rest and during exercise in patients with heart failure

Aims: Pulmonary hypertension, a marker of poor prognosis in heartfailure, may develop or increase during exercise. We soughtto examine the determinants of pulmonary hypertension at restand during exercise in heart failure patients. Methods and results: Forty-six patients with left ventricular (LV) dysfunction (ejectionfraction: 30 ± 6%) underwent a semi-recumbent, incrementalbicycle exercise Doppler echocardiography. LV systolic and diastolicfunction, pulmonary artery systolic pressure (PASP), functionalmitral regurgitation (MR), and left atrial volume were quantifiedat rest and during exercise. Wide changes in PASP at exercisewere unrelated to PASP at rest (r = 0.12). Independent predictorsof PASP at rest were left atrial volume (P = 0.006), E-wavevelocity (P = 0.02), mitral tenting area (P = 0.005), and mitraleffective regurgitant orifice (ERO) (P = 0.02). The incidenceof dyspnoea was similar in patients with and without moderatelysevere pulmonary hypertension at baseline. At peak exercise,LV ejection fraction (P = 0.03) and mitral ERO (P = 0.008) wereindependently associated with PASP. Patients with a larger exerciseincrease in PASP (>60 mmHg) interrupted frequently exercisefor dyspnoea (70 vs. 27%; P = 0.04). A larger rise in mitralregurgitant volume during exercise emerged as the single determinantof exercise-induced increases in PASP. Conclusion: In patients with HF, left atrial volume, mitral deformation,and mitral regurgitant orifice correlated with pulmonary pressureat rest, whereas dynamic MR and limited contractile reservecorrelated with pulmonary pressure at exercise. The magnitudeof pulmonary pressure during exercise in these patients mainlydepends on dynamic MR.     

Sustained improvement of pulmonary hemodynamics in patients at rest and during exercise after thrombolytic treatment of massive pulmonary embolism

This study assessed the long-term effects of thrombolytic treatment in patients with acute massive pulmonary embolism (PE). Seven patients with PE that followed deep-vein thrombosis underwent pulmonary angiography and pressure measurements before and 6 +/- 3 days (mean +/- SD) and 15 +/- 4 months after treatment with intrapulmonary infusions of urokinase (average dose 1724 U/kg X hr) and heparin (average dose 17 U/kg X hr). Treatment was guided by daily measurements of pulmonary arterial (PA) pressure and was continued until PA pressure had normalized (average of 6 days). Late after treatment patients returned for pulmonary angiographic examination, right heart catheterization at rest and during bicycle exercise, and phlebography of the deep veins of both legs. Pulmonary angiograms showed massive obstruction before therapy (Walsh index 15 +/- 2 points of a maximum of 18 points), which was improved 6 days (3 +/- 3 points) and 15 months (1 +/- 2 points) after therapy. Mean PA pressure declined from 37 +/- 9 to 13 +/- 3 mm Hg after 6 days and to 15 +/- 3 mm Hg after 15 months. No recurrence of PE was observed. In six of seven patients at rest and during bicycle exercise (up to 100 W) in the supine position mean PA pressure and total pulmonary resistance remained within normal limits. Over the short term all patients showed clinical signs of deep-vein thrombosis; 15 months later four patients had normal deep veins, but three patients had still phlebographic signs of old thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD

INTRODUCTION: Inhaled anticholinergic drugs are often recommended for use as a first-line therapy for patients with COPD because they provide similar or more effective bronchodilating actions, as well as fewer side effects. It is not known, however, which class of bronchodilators is more advantageous for pulmonary hemodynamics, particularly during exercise. OBJECTIVES: To compare the effects of oxitropium and fenoterol on pulmonary hemodynamics in patients with COPD at rest and during exercise. PATIENTS: The study participants consisted of 20 consecutive male patients with stable COPD, a mean (+/- SD) age of 68+/-8 years old, and an FEV1/FVC ratio of 47.5+/-10.0%. METHODS: Eleven patients inhaled two puffs of oxitropium, and nine patients inhaled two puffs of fenoterol. Seven members of each group performed incremental exercise using a cycle ergometer. The hemodynamic measurements with right heart catheterization were performed by taking the average of three consecutive respiratory cycles before and after the administration of inhaled bronchodilators at rest and during exercise. RESULTS: At rest, despite a similar improvement of spirometric data with the two drugs, fenoterol, not oxitropium, caused significant increases in heart rate and cardiac output, a decrease in pulmonary vascular resistance, and a deteriorated Pao2. During exercise, however, both drugs similarly attenuated elevations in the mean pulmonary arterial pressure (40+/-12 to 38+/-10 mm Hg by oxitropium, and 41+/-9 to 36+/-9 mm Hg by fenoterol), the mean pulmonary capillary wedge pressure, and the mean right atrial pressure. CONCLUSION: Our findings indicate that both classes of bronchodilators are equally beneficial in the attenuation of right heart afterload during exercise in patients with COPD.     

Respiration in conscious dogs at rest and during exercise.

25 mongrel dogs (average b.w. 24.6 kg) were studied on several occasions at rest and during treadmill exercise of up to 10 mph (15% incline). Minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), tidal volume (VT) and respiratory frequency (f) were determined at rest and at each level of exercise. Individual variability in resting VO2 was considerable (71--695 ml/min). Most often the dogs panted, with VE's above 25 liters/min and f's above 100 min-1. The averate VE/VO2 was 109 at rest. VO2 was linearly related to VE (VO2 = 9.17 VE + 66.9; r = 0.80). Differences in resting VE were largely due to differences in f (f = 3.57 VE + 21.2; r = 0.82). Considerable individual variability in VO2 for a given work load was also observed during exercise. Some dogs showed significant differences in VO2 from experiment to experiment while running at a given treadmill speed. These differences were largely related to the levels of VE. VE/VO2 decreased to 50. We found a leveling off of VO2 (at about 60 ml/min/kg) at treadmill speeds of 5 mph, suggesting that the maximal VO2 in dogs is less than previously reported.     

Oxygen consumption at rest and during exercise in pregnancy.

The oxygen consumption (Vo2) of 12 normal women was measured at monthly intervals during pregnancy and 2, 6 and 12 weeks and 6 months postpartum. At each study session measurements were made sitting at rest, during standard steady-state exercise on a bicycle ergometer, and for 10 minutes of recovery. A significant increase in exercise Vo2 was observed in late pregnancy when compared to paired postpartum values. The oxygen debt incurred by standard exercise was also greater in late pregnancy than 12-14 weeks postpartum.