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PubMed2004

The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure.

OBJECTIVES: We sought to investigate the effects of sildenafil, a phosphodiesterase-5 (PDE(5)) inhibitor, on lung function and exercise performance in chronic heart failure (CHF). BACKGROUND: In CHF, nitric oxide-mediated regulation of lung vascular tone and alveolar-capillary membrane conductance is impaired and contributes to exercise intolerance. The potential for benefits due to increased nitric-oxide availability is unexplored. METHODS: In 16 patients with CHF and 8 normal subjects, we measured-before and 60 min after sildenafil (50 mg) or placebo-ejection fraction, pulmonary hemodynamics, carbon monoxide diffusion capacity (DLco), with its membrane (D(M)) and capillary blood volume (V(c)) subcomponents, endothelial function (brachial reactive hyperemia) at rest, peak oxygen uptake (VO(2)), increments in VO(2) versus work rate (DeltaVO(2)/DeltaWR), changes in ventilation versus CO(2) production (VE/VCO(2)) slope, and recovery VO(2) time constant (tau) on exertion. RESULTS: In CHF, sildenafil did not affect cardiac index, wedge pulmonary pressure, or ejection fraction; it significantly (p < 0.01) decreased pulmonary mean artery pressure (-20.4%) and arteriolar resistance (-45.1%), VE/VCO(2) slope (-9.0%) and recovery tau (-25.8%), and increased (p < 0.01) DLco (+11.1%), D(M) (+9.9%) peak VO(2) (+19.7%), DeltaVO(2)/DeltaWR (+11.0%), and brachial reactive hyperemia (+33.3%). No variations occurred in normal subjects and after placebo. Changes in DLco were related to those in VE/VCO(2) slope (r = -0.71; p = 0.002), and changes in brachial hyperemia correlated with those in DeltaVO(2)/DeltaWR (r = 0.80; p = 0.0002). CONCLUSIONS: This study shows that in CHF PDE(5) inhibition modulates pulmonary pressure and vascular tone, and improves DLco, exercise peak VO(2), aerobic (DeltaVO(2)/DeltaWR) and ventilatory (VE/VCO(2) slope) efficiencies, and oxygen debt (recovery tau). Endothelial mechanisms may underlie these effects.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1988

The transfer factor and its subdivisions in patients with pulmonary emboli.

The carbon monoxide transfer factor and its subdivisions, the pulmonary membrane diffusing capacity and the pulmonary capillary volume were measured in fourteen subjects following submassive pulmonary emboli, as demonstrated by a ventilation-perfusion scan, and in fourteen matched controls. Transfer factor and alveolar volume were significantly lower in patients with pulmonary emboli (p less than 0.02). Patients were given six weeks anticoagulant therapy and the measurements repeated three months later. There was a significant increase in the transfer factor and the alveolar volume (p less than 0.01) and the membrane diffusing capacity (p less than 0.05). It has previously been assumed that the reduction in the transfer factor following a pulmonary embolus is due to a reduction in the pulmonary capillary volume. Results of this study however, suggest that it is more likely to be due to a loss of alveolar volume, at least in subjects with submassive emboli.

Adult↗
PubMed1988

Carbon monoxide diffusing capacity in asthmatic patients with mild airflow limitation.

The aim of this study was to test the hypothesis that carbon monoxide diffusing capacity (DCO) is elevated in asthmatic patients with minimal airflow limitation and/or hyperinflation; the latter factors should reduce the possibility of technical errors in the measurement of DCO. In ten asthmatic and ten healthy subjects, DCO and its components, membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Qc) were measured by the single-breath method. Values were normalized for alveolar volume (VA). The mean DCO/VA was higher in the asthma groups as was the Qc/VA. The Dm/Qc was also higher in the asthma group. In the asthmatic but not the healthy subjects, both DCO/VA and Qc/VA were negatively correlated with the forced expiratory flow at 50 percent of vital capacity and peak inspiratory flow rate. Thus, DCO/VA may be increased in asthmatic patients with only mild airflow limitation; this may be due to an elevated capillary blood volume.

Adult↗
PubMed1995

The effect of menstruation on the pulmonary carbon monoxide diffusing capacity.

We studied variations in DLCO during the menstrual cycle in 14 healthy women with a mean age of 29 (SD, 7) yr. Eight were using oral contraceptives, and six were not. DLCO was determined 1 to 7 d before the onset of menses, daily during each of the first 4 d of menses, and 5 to 10 d after onset of menses. In both groups of subjects, the highest values for DLCO were obtained before menses, the lowest were on the third day of menses, whereas after completion of menses the values increased but were not as high as prior to menses. The mean DLCO for all subjects was 23.1 (SD, 3.2) ml/min/mm Hg before menses, 20.9 (SD, 3.0) on the third day of menstruation, and 21.6 (SD, 3.3) 5 to 10 d after onset of menses. The mean percent difference between DLCO before and on the third day of menses in all 14 subjects was 9.2 (SD, 4.4) %. There were no significant changes in hemoglobin on these days to account for the changes in DLCO. Pulmonary capillary blood volume determined in 10 of the subjects did not show a significant change. It is concluded that DLCO can vary significantly during the menstrual cycle, with the highest values occurring prior to menses and the lowest values occurring on the third day of menses, with a mean difference between them of 9%. These variations need to be considered when evaluating DLCO in female patients in the menstrual age group.

Adult↗
PubMed1978

Pulmonary gas exchange, diffusing capacity in natives and newcomers at high altitude.

At high altitude, in resting conditions, no differences have been observed between High Altitude Natives (HAN) and acclimatized Sea Level Natives (SLN) in AaDO2, aADCO2 or venous admixture. In acclimatized SLN, AaDO2 is smaller than at sea level because of: (1) The minor effect on arterial oxygenation of the probably constant venous admixture. (2) The reduction of VA/Q inequality as shown by a smaller aADCO2. In HAN, DLCO is greater than in SLN; the contribution of DM or VC in this difference remains unsettled, mainly because of the difficulties of measurement of DM and VC in HAN suddenly exposed to acute hyperoxia. In SLN, in acute hypoxia, DLCO increased transitorily. Asynchronous mechanisms of adaptation to high altitude are evoked.

Acclimatization↗
PubMed2000

Pulmonary function after exercise with special emphasis on diffusion capacity.

The present work focuses on pulmonary gas exchange during repeated rowing to exhaustion and the recovery of pulmonary diffusion capacity for carbon monoxide (DL) after exercise in healthy young subjects. The components of DL are examined at rest using the single breath method at two different alveolar O2 tensions. Electrical impedance and 99mTechnetium labelled erythrocytes were used to evaluate the recovery of blood distribution. Special attention has been given to the role of the inspiratory muscles as a limiting factor for VO2max and performance. The documentation in this study of a reduced DL several hours after exercise conflicts with the prerequisites of optimal conditions for high metabolic rates in elite athletes. Even low intensity exercise induces a reduction in DL, and together with the fact that a diuretic does not attenuate this decrease, emphasises that the reduction in DM is not due to an interstitial pulmonary edema. The major part of the reduction is due to a decreased CBV reflected in a reduction of VC and a minor part is caused by an injury to the membrane component carried over from exercise. The ability in athletes to repeat exhaustive exercise within 2 h indicates that the slow recovery of DL is not combined with either impaired pulmonary gas exchange or performance. Thus, an acute diffusion limitation and a low pH cause the desaturation in some athletes during exhaustive exercise. Despite the inspiratory muscles having a slower response to endurance training compared with the cardiovascular system, selective training of the inspiratory muscles does not improve either VO2max or performance. This indicates that maximal inspiratory pressure is not a limiting factor for maximal exercise and that the stimuli to increase VA depends on an increased metabolic rate; stressing the role of the peripheral chemoreceptors. Together with the post-exercise decrease in ANP, the reduction in DL may be involved in the mechanism increasing the total blood volume in endurance trained athletes.

Adolescent↗
PubMed2000

Partial improvement in pulmonary function after successful percutaneous balloon mitral valvotomy.

STUDY OBJECTIVES: This study was performed to assess the changes in pulmonary function after a successful percutaneous balloon mitral valvotomy (PBMV) in 23 consecutive patients with symptomatic mitral stenosis. METHODS AND RESULTS: Lung function preprocedure and postprocedure were evaluated by spirometric flow, static pulmonary volumes, and diffusion capacity of the lung for carbon monoxide (DLCO). At baseline, a reduction in small airways flow (maximal expiratory flow at 50% of vital capacity, 70 +/- 29% of predicted value; maximal expiratory flow at 25% of vital capacity, 55 +/- 26% of predicted value) and an increase in DLCO (118 +/- 29%) and Krough Index (KCO; 123 +/- 29% of predicted value) were observed. PBMV caused an improvement in hemodynamic parameters with an increase in mitral valve area (from 1.0 +/- 0.3 to 1.9 +/- 0.5 cm(2); p < 0.001) and a decrease in left atrial pressure (from 17 +/- 3 to 12 +/- 5 mm Hg; p < 0.001). These changes were associated with a significant increase in FVC (from 2.8 +/- 0.84 to 2.9 +/- 0.80 L; p < 0.05) and in FEV(1) (from 2.2 +/- 0.72 to 2.3 +/- 0.68 L; p < 0.05). A decrease in DLCO was observed after PBMV (from 26.7 +/- 7 to 22.5 +/- 5.4 mL/min/mm Hg; p < 0.001; and KCO, from 6.2 +/- 1.4 to 5.2 +/- 1.2 mL/min/mm Hg/L; p < 0.001). No significant changes in small airways flow were detected, suggesting only a partial improvement in pulmonary congestion. CONCLUSION: We conclude that the initial impairment of lung function in patients with symptomatic mitral stenosis is only partially ameliorated by PBMV.

Adult↗
PubMedDate not supplied

Fractional carbon monoxide uptake and "diffusing capacity" in models of pulmonary maldistribution.

Two models of pulmonary non-uniformity have been studied to determine the effects of maldistribution on "diffusing capacity", measured by steady state (DSS) and single breath (DSB) methods, and on the fractional carbon monoxide uptake (U). The distribution of ventilation with respect to lung volume, perfusion and diffusing capacity, as well as breath-holding time, series inhomogeneity and sequential emptying, variously affect DSS and DSB. Of these, only the distribution of ventilation with respect to diffusing capacity (V/D) influences U. In addition, U is very sensitive to dead space ventilation and thus to respiratory frequency, and this is the chief defect of this very simple measurement. The models described indicate ways in which frequency dependence of U may be allowed for, leaving total diffusing capacity and V/D distribution as its sole determinants.

Carbon Monoxide↗
PubMed1987

Alveolar-capillary diffusion of oxygen in dogs exercising in hypoxia.

To detect and quantify diffusion limitation in alveolar-capillary O2 transfer, measurements of pulmonary gas exchange were performed in 6 awake, chronically tracheostomized dogs (mean body weight 28.3 kg) breathing low O2 (arterial PO2 35-39 Torr), with or without CO2 added to inspired gas. From rest to exercise, with O2 uptake averaging 23 ml/(min X kg), the ideal-alveolar-to-arterial PO2 difference (PAiO2-PaO2) increased from 2.1 +/- 0.2 Torr (mean +/- SE) to 2.9 +/- 0.2 in hypoxia, and from 1.9 +/- 0.7 Torr to 3.0 +/- 0.5 in hypercapnic hypoxia. The apparent pulmonary O2 diffusing capacity (DLO2), calculated from O2 uptake, mixed-venous PO2, arterial PO2, and ideal-alveolar PO2, was found to be increased by hypercapnia and exercise. During exercise DLO2 averaged 74 ml/(min X Torr) in hypoxia and 76 ml/(min X Torr) in hypercapnic hypoxia. Because of the influence of inhomogeneity effects, these values should be considered as minimum values for the true pulmonary O2 diffusing capacity. When compared to the pulmonary CO diffusing capacity (DLCO) previously determined by C18O rebreathing in the same dogs in similar conditions, the DLO2/DLCO ratio averaged 1.2, thus being in accordance with the value predicted from the corresponding Krogh diffusion constant ratio. It is concluded that the DLO2 and DLCO values determined drug exercise in hypoxia may be considered to represent acceptable measures for alveolar-capillary diffusion conductance of lungs.

Animals↗
PubMed2000

[Effects of -30 degrees head down tilt on lung function].

OBJECTIVE: To investigate the effects of short-term simulated weightlessness on lung function in healthy males. METHOD: -30 degrees head down tilt for 45 min was used to simulate short-period weightlessness. Lung function of 12 healthy males, aged 18-21, were studied with plethysmography during seating, supine and head down tilt positions. At the same time, blood flow in pulmonary artery and function of right ventricle were measured with Doppler Echo-Cardiography. Comparative analysis was done. RESULT: As body position changed from seating or supine into head down tilt, FVC, FEV1, FEV1%, MVV, VA and IVC decreased. The change of MVV was the most prominent (P < 0.000). As the position changed, pulmonary diffusion increased dramatically (DL(CO) P<0.001, K(CO) P<0.000). CONCLUSION: HDT may lead to a decrease of pulmonary ventilation and lung capacity. The increased pulmonary diffusion might be related to uniform distribution of pulmonary blood flow and increased effective pulmonary vascular bed.

Adolescent↗
PubMed1988

Noninvasive diffusing capacity and cardiac output in exercising dogs.

We have developed a rebreathing procedure to determine diffusing capacity (DLCO) and pulmonary blood flow (Qc) in the awake, exercising dog. A low dead space, leak-free respiratory mask with an incorporated mouthpiece was utilized to achieve mixing between the rebreathing bag and the dog's lung. The rebreathing bag was initially filled with approximately 1.0 liter of gas containing 0.6% C2H2, 0.3% C18O, 9% He, and 35-40% O2. End-tidal gas concentrations were measured with a respiratory mass spectrometer. The disappearance of C2H2 and C18O was measured with respect to He to calculate Qc and DLCO. Values for DLCO in dogs, expressed per kilogram of body weight, were much larger than those reported in humans. However, at a given level of absolute O2 consumption, measurements of absolute DLCO in dogs were comparable to those reported in humans by both rebreathing and steady-state methods at rest and near-maximal exercise. These results suggest that DLCO is more closely matched to the metabolic capacity (i.e., maximal O2 consumption) than to body size between these two species.

Animals↗
PubMed1983

Bleomycin-induced changes in the carbon monoxide transfer factor of the lungs and its components.

To study subclinical pulmonary toxicity of bleomycin we measured the single-breath carbon monoxide transfer factor (TLCO) and its components, pulmonary capillary blood volume (Vc), diffusing capacity of the alveolar-capillary membrane (Dm), and vital capacity (VC) in a homogenous group of 18 patients with testicular nonseminomatous germ cell tumor treated with bleomycin, vinblastine, and cis-diammine-dichloroplatinum (DDP). The most prominent finding was a substantial decrease in Vc (p less than 0.001) with only minor, though significant, changes in the other parameters. No recovery of pulmonary function had taken place 4 months after the last dose of bleomycin. The importance of correcting TLCO for hemoglobin concentration is shown. We conclude that vascular damage may be an important feature of subclinical pulmonary injury caused by bleomycin given in combination with vinblastine and DDP. In the postbleomycin phase, other forms of potentially lung-toxic treatment should be instituted with care.

Adult↗