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Biomedical subjects

R A Matthay

Publications and source records attributed to R A Matthay.

At least 73 records · Page 4Linked to original sources

Determination of cardiac output at rest and during exercise by carbon dioxide rebreathing method in obstructive airway disease.

We evaluated the accuracy of the CO2 rebreathing method (CO2rb) for measuring cardiac output at rest and during steady-state exercise in 15 patients (mean +/- SD age, 59.7 +/- 7.5 yr) with obstructive airway disease. At rest, there was a significant correlation between direct Fick and CO2rb methods using measured arterial PCO2 (r = 0.70; p = 0.002), but not with using end-tidal PCO2 (r = 0.38; p = NS). During exercise, there was greater correlation with CO2rb using arterial PCO2 (r = 0.79; p = 0.001) than using end-tidal PCO2 (r = 0.63; p = 0.007) compared with the direct Fick determination. Correlation between the CO2rb and direct Fick methods was greater with moderate air-flow obstruction (n = 6) than with severe airway disease (n = 9), and the CO2rb method was more accurate during exercise than at rest. The CO2rb method using either end-tidal or arterial PCO2 underestimated the direct Fick measurement in 13 of 15 patients at rest, which may reflect inadequate equilibration between alveolar and oxygenated mixed venous PCO2. However, no consistent error was observed during exercise when higher CO2 production and an increased venoarterial PCO2 difference would diminish potential inaccuracies. We concluded that the CO2rb technique is an acceptable method for measuring cardiac output during exercise in patients with moderate and severe obstructive airway disease as long as arterial PCO2 is directly measured rather than estimated from end-tidal PCO2.

Aged↗

Effects of theophylline on cardiovascular performance in chronic obstructive pulmonary disease.

Theophylline is a widely used bronchodilator, but only recently have its positive cardiovascular actions been recognized in patients with chronic obstructive pulmonary disease (COPD). Intravenous aminophylline acutely reduces pulmonary artery pressures and pulmonary vascular resistance and increases both right and left ventricular ejection fraction. Oral long-acting theophylline produces a similar and chronic improvement in biventricular performance. Postulated mechanisms by which theophylline enhances right and left ventricular systolic pump performance include reduction in ventricular afterload and positive effects of the drug on ventricular inotropy. Theophylline may be particularly valuable in patients with a combination of COPD, pulmonary artery hypertension, and right or left heart failure.

Administration, Oral↗

Acute right heart failure.

The pathophysiology of acute right heart failure, determined largely from experimental animal studies, is outlined. The authors also discuss clinical settings in which acute right ventricular failure may occur and methods for assessing right ventricular function. A physiologic approach to the treatment of acute right heart failure in patients is provided.

Acute Disease↗

Noninvasive diagnosis of pulmonary arterial hypertension in chronic obstructive pulmonary disease: right ventricular ejection fraction at rest.

Because right ventricular ejection fraction (RVEF) depends on impedance to RV ejection, the hypothesis was tested that an abnormality in radionuclide-determined RVEF would be a useful noninvasive predictor of pulmonary artery (PA) hypertension in patients with chronic obstructive pulmonary disease (COPD). Simultaneous measurements of resting RVEF and PA pressure were made in 30 patients with COPD. All were stable and without clinical evidence of respiratory decompensation or congestive heart failure. Eleven patients had normal (less than 20 mm Hg) mean PA pressure and 19 patients had PA hypertension. The average RVEF was 41 +/- 7% (range 29 to 60%). Five patients had normal (greater than 45%) and 25 patients depressed RVEF. An inverse linear relation between mean PA pressure and RVEF was present (r = -0.74). In the group with normal PA pressure, RVEF averaged 48% (range 42 to 60%). In the group with PA hypertension, RVEF averaged 36% (range 29 to 44%). RVEF was significantly higher in the group with PA hypertension. Using RVEF less than 45% as an indicator of PA hypertension, the sensitivity was 100%, the specificity 55%, and the predictive accuracy of a positive result 79%. Using RVEF less than or equal to 40% as an indicator of PA hypertension, the sensitivity was 75%, the specificity 100%, and the predictive accuracy of a positive study 100%. Thus, radionuclide-determined RVEF using the first-pass technique and a multicrystal camera is a useful noninvasive test for diagnosing PA hypertension in patients with advanced COPD.

Adult↗

Relationship between oxygen uptake and oxygen transport in stable patients with chronic obstructive pulmonary disease. Physiologic effects of nitroprusside and hydralazine.

This study was designed to determine whether alterations in systemic oxygen transport induced by the use of vasodilators for pulmonary hypertension would simultaneously affect oxygen uptake in patients with chronic obstructive pulmonary disease (COPD). Six stable patients with moderate to severe COPD were studied during resting conditions, nitroprusside infusion, a second control period, and after administration of hydralazine. Systemic oxygen transport fell with nitroprusside infusion (523 +/- 94 to 418 +/- 78 ml/min/m2, p less than 0.05). With this there was a fall in oxygen uptake (135 +/- 11 to 119 +/- 12 ml/min/m2, p less than 0.05), but only a minimal increase in oxygen extraction. In contrast, systemic oxygen transport was augmented in all patients when hydralazine was administered (444 +/- 121 to 840 +/- 157 ml/min/m2, p less than 0.05). There was also a net increase in oxygen uptake in these patients (122 +/- 19 to 148 +/- 21 ml/min/m2, p less than 0.05). We postulate that these clinically stable patients have a resting oxygen uptake that may become dependent on systemic oxygen transport whenever the latter decreases. This phenomenon has been described previously only in patients with adult respiratory distress syndrome, and it is important to consider when designing studies of pharmacologic therapy for COPD complicated by pulmonary hypertension.

Aged↗

Demonstration of a free elastolytic metalloenzyme in human lung lavage fluid and its relationship to alpha 1-antiprotease.

Although the human alveolar macrophage in tissue culture can secrete an elastolytic metalloenzyme that is not inactivated by alpha 1-antiprotease (AAP), levels of this proteolytic activity and its relationship to AAP in human lung lavage fluid ( HLF ) are unknown from previous studies. Therefore, we measured elastolytic activity in concentrated (20- to 30-fold) HLF from 15 smokers and 10 nonsmokers and related results to measurements of AAP in these fluids. Activity (mean +/- SEM) against a C elastin substrate (expressed as nanograms of porcine pancreatic elastase equivalents per milligram of lavage fluid protein) in smokers, 18.9 +/- 6.7, significantly exceeded (p = 0.05) levels present in nonsmokers, 4.4 +/- 1.8. With the synthetic elastin-like chromophore substrate succinyl-trialanine-nitroanilide ( SLAPN ), activity in individual samples was reduced 79% by EDTA, a metalloproteinase inhibitor, whereas activity was reduced by only 29% in the presence of PMSF, a serine proteinase inhibitor. In addition, using a pooled sample of HLF and C elastin substrate, 80% of activity against the elastin substrate was eliminated by EDTA, whereas 51% was eliminated by PMSF. The activity measured with C elastin substrate correlated inversely with antigenic AAP (r = -0.05, p = 0.01), but no correlations were found between this activity and HLF cell number, cell viability, differential count, or subject smoking history. The detection of activity with C elastin in HLF , with primarily a metalloenzyme inhibitor profile, in the presence of antigenically detectable AAP, may have pathogenetic relevance for emphysema in humans.

Adult↗

Right ventricular performance and central circulatory hemodynamics during upright exercise in patients with chronic obstructive pulmonary disease.

A combined hemodynamic and radionuclide approach was used to evaluate right ventricular performance during upright exercise in 12 male patients with chronic obstructive pulmonary disease. To assess the influence of intrathoracic pressure on hemodynamic parameters, pleural pressure was measured using an esophageal balloon. Mean age was 58.5 +/- 6.7 yr (+/- SD), and all had dyspnea on physical exertion. For the group, forced expiratory volume in one second (FEV1) was 1.04 +/- 0.40 L and arterial oxygen-tension (PaO2) was 77 +/- 11 mmHg. During steady-state, upright exercise on the bicycle ergometer at 58% of maximal oxygen consumption (VO2 max): (1) mean pulmonary artery pressure (Ppa) and pulmonary vascular resistance index (PVRI) increased significantly; (2) right ventricular ejection fraction (RVEF) failed to augment appropriately (less than 5% increase); and (3) right ventricular end-diastolic volume index (RVEDVI) increased significantly, whereas right ventricular end-systolic volume index (RVESVI) did not change. A diminished pulmonary vascular bed, the change in PaO2, and possibly increased alveolar pressure appeared to contribute to the increased load placed on the right ventricle. Both RVEDVI and RVESVI were significantly correlated with Ppa at rest and during exercise. In 2 of the 12 patients, stroke volume index and left ventricular end-diastolic volume index showed minimal change with exercise. VO2max was correlated with the FEV1 (r = 0.75; p = 0.01) as well as resting (r = -0.60; p = 0.02) and exercise (r = -0.61; p = 0.02) PVRI. These results suggest that exercise performance may be limited by right ventricular dysfunction in addition to respiratory impairment in some patients with chronic airway disease.

Aged↗

Bronchial lavage proteins as correlates of histopathologic airway changes in healthy smokers and patients with pulmonary carcinoma.

Cigarette smoking is known to be an important etiologic factor in several lung diseases; however, the number of smokers who develop these diseases represents a small segment of the smoking population. It is possible that evidence of inhalation-induced injury to bronchial epithelial cells of smokers will be reflected in the proteinaceous products of these cells, thereby identifying a high-risk subgroup. We have tested this hypothesis by analysis of 2 proteins, free secretory component (FSC) and the keratins, in lavage fluids obtained from 4 groups of subjects: 30 normal nonsmokers, 15 asymptomatic smokers, 22 symptomatic smokers, and 40 carcinoma patients. Among symptomatic smokers, FSC relative to total protein (FSC/TP) was depressed compared with that in nonsmokers and asymptomatic smokers. The keratins were detected only in symptomatic smokers and correlated with pack/years of smoking history (p = 0.017). Carcinoma patients had depressed FSC/TP and detectable keratin (33 of 38 patients studied). Lung sections from carcinoma patients studied immunohistochemically revealed an apparent inverse relationship between tissue FSC and keratins. This inverse relationship was borne out by analysis of these proteins in the lavage fluid of cancer patients (r = -0.4, p = 0.04). Thus, in cancer patients, immunohistochemical evidence of airway injury correlates with bronchial lavage levels of mucosal epithelial cell proteins. It is possible that smokers with altered levels of these proteins may be the ones at increased risk of smoking-associated lung disease.

Adolescent↗

Neurogenic pulmonary edema.

A variety of central nervous system (CNS) insults may be complicated by the acute development of pulmonary edema. This occurrence has been termed neurogenic pulmonary edema (NPE), and experimental models have clearly shown that CNS insults may cause pulmonary edema. Unfortunately, the pathophysiologic aspects of this response are not clearly understood. Basing an approach to the development of pulmonary edema on Starling's equation leads to the conclusion that NPE is caused by changes in pulmonary endothelial permeability and/or microvascular pressures. It was previously suggested (the "blast theory") that CNS insults caused acute systemic arterial and pulmonary venous spasm and increased venous return, which would result in a severe pulmonary vascular hydrostatic insult and a secondary permeability defect. Although such hydrostatic derangements may explain certain cases of NPE, recent clinical and experimental studies have indicated that CNS disorders may cause a permeability defect without a vascular insult. The mediating factor for a permeability defect is not clear. The implications of these findings are that NPE may be caused by either permeability abnormalities or hydrostatic insults, may present clinically in a variety of ways, and may require different approaches to treatment. Our understanding of the CNS sites that might mediate NPE is not sophisticated enough, at present, to define the neural mechanisms involved in the pathogenesis of NPE.

Animals↗

Cardiovascular-pulmonary monitoring in the intensive care unit (Part 2).

Proliferation of technology in the ICU likely will continue at a rapid pace. This presents a strong challenge to the clinician's task of "above all, do not harm." While invasive techniques carry obvious direct risks, both invasive and noninvasive monitoring present a more subtle threat. Pitfalls in the acquisition and interpretation of data must be recognized before appropriate therapeutic decisions can be made. Advanced monitoring devices and techniques must supplement and not supplant clinical assessment.

Arrhythmias, Cardiac↗

Bronchoalveolar lavage. Its safety in subjects with mild asthma.

It has been suggested that fiberoptic bronchoscopy may induce life-threatening bronchospasm in persons with asthma. The safety of bronchoscopy and bronchoalveolar lavage (BAL) with bilateral installation of 300 ml of saline solution was assessed prospectively in ten adults with mild asthma as a part of a study of the lower respiratory tract in bronchospastic disease. Asthmatic subjects had pretreatment with intravenous aminophylline prior to bronchoscopy. Pulmonary function tests were performed prior to and immediately after the procedure, and values were compared to results in 12 normal adults undergoing bronchoscopy with BAL. One subject had mild bronchospasm (the third subject) before BAL could be performed. There were no major complications in the remaining asthmatic or normal subjects. Mean forced expiratory volume in one second (FEV1) did not change significantly in either group, and the mid-flow rate at 50 percent of vital capacity (Vmax 50%) decreased significantly only in normal subjects (p = 0.002). Moreover, none of the nine asthmatic subjects completing bronchoscopy with BAL had clinically significant bronchospasm. These results suggest that elective fiberoptic bronchoscopy and BAL can be performed safely in subjects with mild asthma.

Adult↗

Exercise impairment in chronic obstructive pulmonary disease.

This article reviews factors that may limit exercise performance in patients with COPD. These factors include alteration in pulmonary mechanics, respiratory muscle fatigue, impairment in pulmonary gas exchange, abnormal perception of breathlessness and ventilatory control, cor pulmonale, and poor nutritional status. The clinical application of exercise testing in patients with COPD and the role of various therapeutic modalities in altering exercise performance in COPD are discussed.

Diaphragm↗

Contrasting acute effects of vasodilators (nitroglycerin, nitroprusside, and hydralazine) on right ventricular performance in patients with chronic obstructive pulmonary disease and pulmonary hypertension: a combined radionuclide-hemodynamic study.

Fourteen patients with chronic obstructive pulmonary disease, mild to moderate pulmonary hypertension, and diminished right ventricular (RV) ejection fraction were studied acutely with use of a combined radionuclide-hemodynamic approach to assess and contrast the effects of 3 vasodilators on RV performance and central hemodynamic function. Nitroglycerin significantly decreased mean right atrial pressure, RV end-diastolic volume index, mean pulmonary artery pressure, cardiac index, and arterial oxygen tension, but did not affect pulmonary vascular resistance index and increased RV ejection fraction. Nitroprusside had similar effects on mean right atrial pressure, RV end-diastolic volume index, mean pulmonary artery pressure, cardiac index, and arterial oxygen tension, but also mildly decreased pulmonary vascular resistance index and did not alter RV ejection fraction. In contrast, hydralazine decreased pulmonary vascular resistance index and increased cardiac index and RV ejection fraction. The increase in ejection fraction correlated well with the decrease in pulmonary vascular resistance. These data suggest that in patients with mild to moderate secondary pulmonary hypertension, acute administration of hydralazine results in a substantial improvement in RV performance by virtue of decreasing pulmonary vascular resistance. In contrast, nitroglycerin and nitroprusside demonstrate predominant effects that reduce preload, cardiac index, and arterial oxygen tension. Based on these data, afterload reduction with vasodilators such as hydralazine may be potentially useful in selected patients with pulmonary disease and secondary pulmonary hypertension and appear preferable to agents that primarily reduce preload. Further long-term studies are necessary to establish therapeutic efficacy.

Adult↗

Noninvasive assessment of right and left ventricular function in acute and chronic respiratory failure.

This review evaluates noninvasive techniques for assessing cardiovascular performance in acute and chronic respiratory failure. Radiographic, radionuclide, and echocardiographic methods for determining ventricular volumes, right (RV) and left ventricular (LV) ejection fractions, and pulmonary artery pressure (PAP) are emphasized. These methods include plain chest radiography, radionuclide angiocardiography, thallium-201 myocardial imaging, and M mode and 2-dimensional echocardiography, which have recently been applied in patients to detect pulmonary artery hypertension (PAH), right ventricular enlargement, and occult ventricular performance abnormalities at rest or exercise. Moreover, radionuclide angiocardiography has proven useful in combination with hemodynamic measurements, for evaluating the short-and long-term cardiovascular effects of therapeutic agents, such as oxygen, digitalis, theophylline, beta-adrenergic agents, and vasodilators.

Angiography↗

Comparison of bacterial adherence to ciliated and squamous epithelial cells obtained from the human respiratory tract.

Previous in vitro studies have suggested that bacterial adherence to buccal squamous epithelial cells may be a mechanism involved in postoperative colonization of the oropharynx. However, the relationship between bacterial binding to oral epithelial and ciliated respiratory cells is unknown. To investigate bacterial binding to other cells in the human respiratory tract, we measured adherence of Pseudomonas seruginosa to ciliated cells (from nose and trachea) and compared this to squamous cells (from buccal mucosa), Cell samples were collected from 16 noncolonized individuals undergoing either elective surgery or volunteer bronchoscopy. Adherence (mean +/- SEM) to tracheal cells (4.6 +/- 0.8 bacteria per cell) and to nasal cells (4.7 +/- 0.6 bacteria per cell) was similar. These values significantly (p less than 0.001) exceeded buccal cell adherence (0.9 +/- 0.2 bacteria per cell). Because cells from ciliated surfaces bind more bacteria than cells from squamous surfaces, bacterial adherence at these respiratory sites may involve different mechanisms. The enhanced bacterial attachment to ciliated cells may assume pathogenic importance when mucociliary function is impaired.

Acetylcysteine↗

Air-space immunoglobulin production and levels in bronchoalveolar lavage fluid of normal subjects and patients with sarcoidosis.

The purpose of this study was to examine the relationship between immunoglobulin production and immunoglobulin levels in bronchoalveolar lavage (BAL) fluid and serum of normal subjects and patients with sarcoidosis. Eleven normal volunteers and 17 patients were studied. In normal subjects, no important relationship existed between the number of immunoglobulin-secreting cells and immunoglobulin levels in BAL or serum. By contrast, in patients with sarcoidosis, a highly significant correlation existed between the number of IgG secreting cells and IgG/alb% in BAL (p = 0.008) and between the number of IgG secreting cells in BAL and serum IgG mg/ml (p = 0.002). Similar associations did not exist for IgA and IgM. These data demonstrate for the first time the relationship between immunoglobulin production and immunoglobulin levels in normal persons, and convincingly show that immunoglobulin production at sites of disease activity is responsible for hypergammaglobulinemia in BAL and serum of patients with sarcoidosis.

Adult↗