Biomedical subjects

D G McBrayer

Publications and source records attributed to D G McBrayer.

4 recordsLinked to original sources

PubMed1997

Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus.

BACKGROUND: We studied cardiopulmonary function during exercise in young subjects with long-standing insulin-dependent diabetes mellitus (IDDM) who have no clinical cardiopulmonary disease to determine the relationships of aerobic capacity, gas exchange, ventilatory power requirement, and cardiac output to chronic glycemic control. METHODS: Eighteen subjects with IDDM and 14 normal control subjects were studied. Nine diabetic subjects received twice daily insulin injections and had chronically elevated levels of glycosylated hemoglobin (hyperglycemic group); 9 other diabetic subjects received insulin via continuous infusion pumps and maintained chronic near-normal levels of glycosylated hemoglobin (normoglycemic group). At the end of at least 7 years of regular follow-up, aerobic capacity was determined by cycle ergometry. Lung volume, diffusing capacity, and cardiac output during exercise were measured by a rebreathing technique. Ventilatory power was measured by the esophageal balloon technique. RESULTS: Maximal work load and oxygen uptake were markedly impaired in chronically hyperglycemic diabetic patients associated with significant restrictions of lung volume, lung diffusing capacity, and stroke index during exercise. Membrane diffusing capacity was significantly reduced at a given cardiac index. The normoglycemic patients consistently showed less impairment than the hyperglycemic patients. CONCLUSION: Physiologically significant cardiopulmonary dysfunction develops in asymptomatic patients with long-standing IDDM. Chronic maintenance of near-normoglycemia is associated with improved cardiopulmonary function.

Adult↗

PubMed1995

Reference values of pulmonary diffusing capacity during exercise by a rebreathing technique.

Normal reference values of the pulmonary diffusing capacity for carbon monoxide (DLCO), diffusing capacity of the membrane (DMCO), and pulmonary capillary blood volume (VC) were derived by a rebreathing technique in 44 normal, healthy, nonsmoking individuals ranging from 17 to 68 yr of age. Simultaneous measurements of DLCO, lung volumes, pulmonary blood flow, and septal tissue volume were determined at rest and during steady-state exercise of 25, 50, and 80% of maximal workload and at two levels of alveolar O2 tension. DMCO and VC were calculated using the Roughton-Forster relationship. Using stepwise regression analysis, DLCO and DMCO (in ml CO/min/mm Hg) were found to be significantly related to pulmonary blood flow (Qc in L/min), age (in years), and body surface area (BSA in square meters). VC (in ml) was found to be significantly related to QC and BSA. Normalization of measured data with respect to these variables largely eliminated male versus female differences. We conclude that QC is the most important determinant of the recruitment of diffusing capacity. From rest to near-maximal exercise, DLCO, DMCO, and VC increase linearly with respect to QC without evidence of reaching a plateau.

Adolescent↗

PubMed1994

Na-K-Cl cotransport in nystatin-treated tracheal cells: regulation by isoproterenol, apical UTP, and [Cl]i.

Chloride secretion in mammalian airway epithelia is stimulated by beta-adrenergic agonists via an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent mechanism and by apical triphosphate nucleotides (ATP, UTP) via a cAMP-independent mechanism. Both types of secretagogues are known to stimulate apical Cl channels in airway cells; however, to maintain a stimulated rate of secretion, basolateral Cl influx via Na-K-Cl cotransport must be upregulated in parallel with apical Cl efflux. To examine the regulation of basolateral cotransport activity and its relationship to apical Cl efflux, we examined Cl transport in confluent primary cultures of dog tracheal epithelial cells treated with nystatin, an antibiotic that increases the permeability of plasma membranes to small monovalent ions, including Cl. By applying nystatin to the apical membrane of these cultures, apical Cl permeability could be increased to the point where transepithelial Cl transport is limited by transport across the basolateral membrane, which reflects primarily the activity of the cotransporter. In cultures of tracheal cells not treated with nystatin, transepithelial (basolateral-to-apical) 36Cl flux was increased two- to threefold by exposure to isoproterenol (5 microM, basolateral) or apical UTP (10 microM). Apical application of nystatin (400 units/ml) increased the basal level of transepithelial 36Cl flux approximately 1.5-fold and eliminated UTP stimulation of this flux, although an approximately twofold stimulation by isoproterenol persisted. Nystatin treatment also abolished UTP stimulation of saturable, basolateral [3H]bumetanide binding, a measure of functioning Na-K-Cl cotransporters in these cells; isoproterenol stimulation of binding was only mildly inhibited by nystatin treatment. Lowering intracellular Cl concentration ([Cl]i) by incubating cultures with apical media containing nystatin and reduced [Cl] (NO3 replacement) increased both basolateral-to-apical 36Cl flux and [3H]bumetanide binding in the absence of secretagogues or cell shrinkage. The results support our previous suggestion, based entirely on [3H]bumetanide binding [M. Haas, D. G. McBrayer, and J. R. Yankaskas. Am. J. Physiol. 264 (Cell. Physiol. 32): C189-C200, 1993], that UTP stimulation of basolateral Na-K-Cl cotransport in airway epithelial cells is entirely secondary to, and requires, an increase in apical Cl efflux, and further suggest that a decrease in [Cl]i may be a signal for cotransport activation in response to UTP. In addition, a cAMP-dependent cascade initiated by isoproterenol appears to directly stimulate the cotransporter.

Animals↗

PubMed1993

Dual mechanisms for Na-K-Cl cotransport regulation in airway epithelial cells.

To investigate cellular mechanisms involved in the regulation of basolateral Na-K-Cl cotransport in airway epithelia, we determined saturable basolateral [3H]bumetanide binding, a measure of functioning cotransporters, in primary cultures of canine tracheal and human nasal epithelial cells, including cells from patients with cystic fibrosis (CF). As we previously reported [M. Haas, L. G. Johnson, and R. C. Boucher. Am. J. Physiol. 259 (Cell Physiol. 28): C557-C569, 1990], isoproterenol and hypertonic cell shrinkage produce an equivalent stimulation of [3H]bumetanide binding to dog tracheal cells. We now find that apical ATP and UTP, which stimulate apical Cl channels and Cl secretion in normal and CF airway cells by an adenosine 3',5'-cyclic monophosphate (cAMP)-independent mechanism (S. J. Mason, A. M. Paradiso, and R. C. Boucher. Br. J. Pharmacol. 103: 1649-1656, 1991), increase basolateral [3H]bumetanide binding to dog tracheal cells to the same extent as do isoproterenol and hypertonic shrinkage. The stimulatory effects of ATP and UTP on binding are inhibited by apical addition of a Cl channel blocker, the indanyloxyacetic acid derivative IAA-94 (0.2 mM), or by raising basolateral K concentration ([K]b) from 3.3 to 40 mM, suggesting these effects are secondary to apical Cl efflux via channels. Apical IAA-94 and increased [K]b also inhibit stimulation of binding by isoproterenol by approximately 50%, suggesting that part (but not all) of the effect of the beta-agonist on basolateral cotransport is secondary to apical Cl efflux, with an additional component of direct stimulation of cotransport via cAMP. In support of this interpretation, we find that isoproterenol and a membrane-permeable cAMP analogue increase [3H]bumetanide binding to primary cultures of CF nasal epithelial cells, in which significant cAMP-mediated stimulation of apical Cl efflux does not occur. [3H]bumetanide binding to CF nasal cells is also stimulated by apical ATP, and levels of saturable [3H]bumetanide binding to CF cells are 1.3-1.5 times those in non-CF nasal cells under both basal and stimulated conditions. The results suggest that basolateral Na-K-Cl cotransport in airway cells may be upregulated in two distinct ways: 1) directly via a cAMP-dependent cascade, and 2) as a secondary response to apical Cl channel activation. Both of these mechanisms appear to be intact in CF.

Adenosine Triphosphate↗