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Biomedical subjects

Peter T Macklem

Publications and source records attributed to Peter T Macklem.

13 recordsLinked to original sources
PubMed2006

Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema.

Diffusion MRI of hyperpolarized (3)He shows that the apparent diffusion coefficient (ADC) of (3)He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about (3)He gas diffusivity in explanted human lungs, and describe the relationship between (3)He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (L(m)) measurements--the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via (3)He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and L(m)). An important result is that restricted (3)He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes.

Administration, Inhalation↗
PubMed2005

Long-range diffusion of hyperpolarized 3He in explanted normal and emphysematous human lungs via magnetization tagging.

Long-range diffusivity of hyperpolarized 3He gas was measured from the decay rate of sinusoidally modulated longitudinal nuclear magnetization in three normal donor and nine severely emphysematous explanted human lungs. This (long-range) diffusivity, which we call Dsec, is measured over seconds and centimeters and is approximately 10 times smaller in healthy lungs (0.022 cm2/s) than the more traditionally measured Dmsec, which is measured over milliseconds and submillimeters. The increased restriction of Dsec reflects the complex, tortuous paths required to navigate long distances through the maze of branching peripheral airways. In emphysematous lungs, Dsec is substantially increased, with some regions showing nearly the unrestricted value of the self-diffusion coefficient (0.88 cm2/s for dilute 3He in air, a 40-fold increase). This suggests the presence of large collateral pathways opened by alveolar destruction that bypass the airways proper. This destruction was confirmed by comparison with histology in seven lungs and by removal of trapped gas via holes in the pleural surface in five lungs.

Emphysema↗
PubMed2004

Complex systems and the technology of variability analysis.

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients.

Critical Illness↗
PubMed2003

Effects of rapid saline infusion on lung mechanics and airway responsiveness in humans.

Lung mechanics and airway responsiveness to methacholine (MCh) were studied in seven volunteers before and after a 20-min intravenous infusion of saline. Data were compared with those of a time point-matched control study. The following parameters were measured: 1-s forced expiratory volume, forced vital capacity, flows at 40% of control forced vital capacity on maximal (Vm(40)) and partial (Vp(40)) forced expiratory maneuvers, lung volumes, lung elastic recoil, lung resistance (Rl), dynamic elastance (Edyn), and within-breath resistance of respiratory system (Rrs). Rl and Edyn were measured during tidal breathing before and for 2 min after a deep inhalation and also at different lung volumes above and below functional residual capacity. Rrs was measured at functional residual capacity and at total lung capacity. Before MCh, saline infusion caused significant decrements of forced expiratory volume in 1 s, Vm(40), and Vp(40), but insignificantly affected lung volumes, elastic recoil, Rl, Edyn, and Rrs at any lung volume. Furthermore, saline infusion was associated with an increased response to MCh, which was not associated with significant changes in the ratio of Vm(40) to Vp(40). In conclusion, mild airflow obstruction and enhanced airway responsiveness were observed after saline, but this was not apparently due to altered elastic properties of the lung or inability of the airways to dilate with deep inhalation. It is speculated that it was likely the result of airway wall edema encroaching on the bronchial lumen.

Administration, Inhalation↗
PubMed2003

Airway wall remodeling: friend or foe?

Airway wall remodeling is well documented for asthmatic airways and is believed to result from chronic and/or short-term exposure to inflammatory stimuli. Airway wall remodeling can contribute to airway narrowing as well as to the airway hyperresponsiveness, which is a characteristic abnormality in asthma. However, the potential for airway narrowing could be much worse if it were not for some of the protective effects of remodeling that may help to limit airway narrowing in asthmatic patients. This minireview discusses the evidence for airway wall remodeling and its effects, friend and/or foe, on airway narrowing in asthmatic patients.

Airway Resistance↗
PubMed2002

Phonospirometry for noninvasive measurement of ventilation: methodology and preliminary results.

We measured tracheal flow from tracheal sounds to estimate tidal volume, minute ventilation (VI), respiratory frequency, mean inspiratory flow (VT/TI), and duty cycle (TI/Ttot). In 11 normal subjects, 3 patients with unstable airway obstruction, and 3 stable asthmatic patients, we measured tracheal sounds and flow twice: first to derive flow-sound relationships and second to obtain flow-volume relationships from the sound signal. The flow-volume relationship was compared with pneumotach-derived volume. When subjects were seated, facing forward and with neck rotation, flexion, and standing, flow-volume relationship was within 15% of pneumotach-derived volume. Error increased with neck extension and while supine. We then measured ventilation without mouthpiece or nose clip from tracheal sounds during quiet breathing for up to 30 min. Normal results +/- SD revealed tidal volume = 0.37 +/- 0.065 liter, respiratory frequency = 19.3 +/- 3.5 breaths/min, VI = 6.9 +/- 1.2 l/min, VT/TI = 0.31 +/- 0.06 l/s, and TI/Ttot = 0.37 +/- 0.04. Unstable airway obstruction had large VI due to increased VT/TI. With the exception of TI/Ttot, variations in ventilatory parameters were closer to log normal than normal distributions and tended to be greater in patients. We conclude that phonospirometry measures ventilation reasonably accurately without mouthpiece, nose clip, or rigid postural constraints.

Airway Obstruction↗
PubMed2002

Determinants of exercise performance in normal men with externally imposed expiratory flow limitation.

To understand how externally applied expiratory flow limitation (EFL) leads to impaired exercise performance and dyspnea, we studied six healthy males during control incremental exercise to exhaustion (C) and with EFL at approximately 1. We measured volume at the mouth (Vm), esophageal, gastric and transdiaphragmatic (Pdi) pressures, maximal exercise power (W(max)) and the difference (Delta) in Borg scale ratings of breathlessness between C and EFL exercise. Optoelectronic plethysmography measured chest wall and lung volume (VL). From Campbell diagrams, we measured alveolar (PA) and expiratory muscle (Pmus) pressures, and from Pdi and abdominal motion, an index of diaphragmatic power (W(di)). Four subjects hyperinflated and two did not. EFL limited performance equally to 65% W(max) with Borg = 9-10 in both. At EFL W(max), inspiratory time (TI) was 0.66s +/- 0.08, expiratory time (TE) 2.12 +/- 0.26 s, Pmus approximately 40 cmH2O and DeltaVL-DeltaVm = 488.7 +/- 74.1 ml. From PA and VL, we calculated compressed gas volume (VC) = 163.0 +/- 4.6 ml. The difference, DeltaVL-DeltaVm-VC (estimated blood volume shift) was 326 ml +/- 66 or 7.2 ml/cmH2O PA. The high Pmus and long TE mimicked a Valsalva maneuver from which the short TI did not allow recovery. Multiple stepwise linear regression revealed that the difference between C and EFL Pmus accounted for 70.3% of the variance in DeltaBorg. DeltaW(di) added 12.5%. We conclude that high expiratory pressures cause severe dyspnea and the possibility of adverse circulatory events, both of which would impair exercise performance.

Adult↗
PubMed2002

Respiratory muscle dynamics and control during exercise with externally imposed expiratory flow limitation.

To determine how decreasing velocity of shortening (U) of expiratory muscles affects breathing during exercise, six normal men performed incremental exercise with externally imposed expiratory flow limitation (EFLe) at approximately 1 l/s. We measured volumes of chest wall, lung- and diaphragm-apposed rib cage (Vrc,p and Vrc,a, respectively), and abdomen (Vab) by optoelectronic plethysmography; esophageal, gastric, and transdiaphragmatic pressures (Pdi); and end-tidal CO2 concentration. From these, we calculated velocity of shortening and power (W) of diaphragm, rib cage, and abdominal muscles (di, rcm, ab, respectively). EFLe forced a decrease in Uab, which increased Pab and which lasted well into inspiration. This imposed a load, overcome by preinspiratory diaphragm contraction. Udi and inspiratory Urcm increased, reducing their ability to generate pressure. Pdi, Prcm, and Wab increased, indicating an increased central drive to all muscle groups secondary to hypercapnia, which developed in all subjects. These results suggest a vicious cycle in which EFLe decreases Uab, increasing Pab and exacerbating the hypercapnia, which increases central drive increasing Pab even more, leading to further CO2 retention, and so forth.

Abdominal Muscles↗