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Biomedical subjects

P T Macklem

Publications and source records attributed to P T Macklem.

At least 19 recordsLinked to original sources
PubMed1992

Effect of negative pressure ventilation in severe chronic obstructive pulmonary disease.

The hypothesis that patients with chronic obstructive pulmonary disease (COPD) have chronic inspiratory muscle fatigue was tested in an effectiveness trial in which negative pressure ventilation (NPV) was used to produce inspiratory muscle rest. In a double-blind study 184 patients with severe COPD were randomly allocated active or sham NPV treatment for a 12-week period of home use. The distance walked in a 6 min walk test was the primary outcome variable. Secondary outcome measures were cycle exercise endurance time, severity of dyspnoea, quality of life, arterial blood gas tensions, and respiratory muscle strength. The percentage reduction in amplitude of the diaphragmatic electromyographic signal multiplied by hours of NPV was used to reflect the dose of NPV so we could examine dose-response relations. Analysis was based on intention to treat. We found no evidence of a clinically or statistically significant difference in any outcome measure between active and sham groups. No dose-response relation was observed. Moreover, the intervention was poorly accepted despite substantial clinical support. We conclude that NPV as used in this study is difficult to apply and ineffective when used with the aim of resting the respiratory muscles in patients with stable COPD.

Aged↗
PubMed1992

Induction of sleep apnoea with negative pressure ventilation in patients with chronic obstructive lung disease.

BACKGROUND: Negative pressure ventilation provides intermittent non-invasive ventilatory assistance for patients with advanced chronic obstructive lung disease. Upper airway obstruction during sleep, a reported complication of the technique, may, however, limit its clinical applicability. METHODS: The effects of nocturnal negative pressure ventilation on ventilation and on indices of sleep quality were investigated in five patients with severe chronic obstructive lung disease (mean (SE) FEV1 31% (3%) predicted) who had completed three months of nightly negative pressure ventilation. Subjects underwent overnight polysomnography on consecutive nights, the first night serving as a control and negative pressure ventilation being provided on the second night. Ventilators were adjusted to result in maximum suppression of the peak phasic electromyogram signal from the diaphragm. RESULTS: Negative pressure ventilation resulted in substantial increases in episodes of obstructive apnoea and hypopnoea (mean (SE)/h 59.3 (19.8) v 3.2 (1.3) on control nights). Most obstructive events, however, were associated with under 3% oxygen desaturation, and the lowest recorded values for overnight oxygen saturation were similar on the two study nights. Negative pressure ventilation was also associated with significant increases in the frequencies of movement arousals and changes in sleep stage. CONCLUSIONS: Negative pressure ventilation applied during sleep to patients with advanced chronic obstructive lung disease may result in the development of recurrent episodes of apnoea and hypopnoea as well as altered sleep quality, which could limit its clinical applicability.

Aged↗
PubMed1992

Effect of fatigue on diaphragmatic function at different lung volumes.

The transdiaphragmatic pressure twitches (PdiT) in response to single maximal shocks delivered bilaterally to the phrenic nerves were recorded as a function of lung volume when the diaphragm was fresh and when fatigued. All relationships were linear and negatively sloped (all r greater than 0.85). From these relationships PdiT was found to decrease with fatigue more rapidly and to recover more quickly at high than at low lung volumes. Complete recovery of PdiT at all lung volumes was greater than 1 h. Contraction and relaxation rate constants of PdiT did not change significantly with fatigue. We conclude that fatigue affects diaphragm contractility more at high than at low lung volumes and that changes in diaphragm contractility are best reflected in the measurement of PdiT as a function of lung volume.

Adult↗
PubMed1992

Analysis of human chest wall motion using a two-compartment rib cage model.

We present a model of chest wall mechanics that extends the model described previously by Macklem et al. (J. Appl. Physiol. 55: 547-557, 1983) and incorporates a two-compartment rib cage. We divide the rib cage into that apposed to the lung (RCpul) and that apposed to the diaphragm (RCab). We apply this model to determine rib cage distortability, the mechanical coupling between RCpul and RCab, the contribution of the rib cage muscles to the pressure change during spontaneous inspiration (Prcm), and the insertional component of transdiaphragmatic pressure in humans. We define distortability as the relationship between distortion and transdiaphragmatic pressure (Pdi) and mechanical coupling as the relationship between rib cage distortion and the pressure acting to restore the rib cage to its relaxed configuration (Plink), as assessed during bilateral transcutaneous phrenic nerve stimulation. Prcm was calculated at end inspiration as the component of the pressure displacing RCpul not accounted for by Plink or pleural pressure. Prcm and Plink were approximately equal during quiet breathing, contributing 3.7 and 3.3 cmH2O on average during breaths associated with a change in Pdi of 3.9 cmH2O. The insertional component of Pdi was measured as the pressure acting on RCab not accounted for by the change in abdominal pressure during an inspiration without rib cage distortion and was 40 +/- 12% (SD) of total Pdi. We conclude that there is substantial resistance of the human rib cage to distortion, that, along with rib cage muscles, contributes importantly to the fall in pleural pressure over the costal surface of the lung.

Adult↗
PubMed1992

Mechanical implications of in vivo human diaphragm shape.

Using magnetic resonance imaging, we measured the three-dimensional form of the diaphragm in vivo in four supine relaxed subjects at functional residual capacity and calculated its total surface area, the right and left surface areas in the zone of apposition, and the principal radii of curvature as a function of height. The area of apposition comprised 45 +/- 1.5% (SE) of the total surface area of the diaphragm. Available data on the area of the central tendon indicate that a considerable part of the muscular part of the diaphragm is lung apposed. The curvature was linearly related to height over 7 cm of the posterior half of each hemidiaphragm. From the linear portion of this graph and assuming a vertical gradient of transdiaphragmatic pressure of 0.75 cmH2O/cm, we applied the Laplace law and calculated tensions of 54 and 32 g/cm for right and left sides, respectively. We conclude that the shape of at least part of the posterior half of the relaxed human diaphragm in the supine position at functional residual capacity can be explained by the Laplace law, suggesting that both the lung and abdominal contents behave sufficiently as fluids so that they do not impose their shape on the diaphragm. Because diaphragm muscle is partly lung apposed, it is unlikely that the diaphragm functions simply as a piston.

Adult↗
PubMed1992

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.

Airway Resistance↗
PubMed1992

Evaluation of human diaphragm contractility using mouth pressure twitches.

Mouth (PmT), esophageal (PesT), and transdiaphragmatic pressure twitches (PdiT) in response to single supramaximal bilateral phrenic nerve shocks were recorded during relaxation between total lung capacity (TLC) and functional residual capacity (FRC) in five normal volunteers. The PmT versus PesT or PmT versus PdiT relationships, which were linearly correlated (all r greater than 0.76), were not affected by diaphragm fatigue and were reproducible on repeated determinations over a period exceeding 1 yr. The PmT versus lung volume relationship was also linear (all r greater than 0.72) and reproducible, and its changes following diaphragm fatigue reliably reflected the changes in diaphragm contractility. We conclude that PmT is a reliable measure of diaphragm pressure-generating capacity in normal individuals and has the potential of providing similar information in patients.

Adult↗
PubMed1992

Vector analysis in partitioning of inspiratory muscle action in dogs.

We considered the displacements and the pressure changes resulting from isolated contraction of 2 muscles as analogous to 2 vectors and those during simultaneous contraction as resultants. These were resolved into contributing components to calculate the contribution of each muscle group and partition the action of inspiratory muscles. Relative displacements of rib cage (delta RC) and abdomen (delta AB) and changes in transpulmonary (delta PL) and abdominal (delta Pab) pressures were obtained during spontaneous breathing, isolated contraction of rib cage muscle (RCM), diaphragmatic (DI), costal and crural diaphragm and passive inflation in 7 dogs. The diaphragm accounted for 58 +/- 19.8% SD of the chest wall displacement and 90 +/- 6.6% SD of the pressure swings during spontaneous breathing. The costal diaphragm accounted for 61 +/- 28.9% SD of the displacement produced by contraction of the entire diaphragm. Despite wide variability in the action of the diaphragm and its components, all animals breathed close to their relaxation characteristic. We conclude that there are marked differences in the degree of RCM recruitment between dogs in order to prevent chest wall distortions.

Animals↗
PubMed1991

Contractile properties of the human diaphragm during chronic hyperinflation.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS: In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS: At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS: The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.

Aged↗
PubMed1991

A randomized clinical trial of negative pressure ventilation in severe chronic obstructive pulmonary disease: design and methods.

This report documents the design and methods of a randomized clinical trial designed to test the effectiveness of home negative pressure ventilation in patients with severe chronic obstructive pulmonary disease. Active negative pressure ventilation was compared with a sham version of the treatment after a pre-trial assessment had indicated the feasibility of the latter. Over 1200 patients in the metropolitan Montreal area were screened. Of these, 348 patients were recruited to enter a 4-week stabilization period, and 184 were subsequently randomized to receive either active or sham negative pressure ventilation. A 5-day in-hospital period was used to train patients in ventilator use and obtain baseline measures of exercise capacity, lung function, respiratory symptoms, and quality of life. Home ventilation treatment took place during a following 12-week period. Respirator use was recorded both from patient logs and from concealed meters installed in the units. Patients received four home visits by physiotherapists during the 12-week period and returned for follow-up to the hospital 4 and 12 weeks post-discharge for reassessment.

Aged↗
PubMed1991

Direct measurement of intracellular pressure.

The feasibility of using the servo-null technique for direct measurement of intracellular pressure (Pin) was investigated. A large cell, the Xenopus laevis oocyte, was chosen for study, and it was established that Pin obtained with this method was both stable and accurate in these cells. Median resting Pin in oocytes was found to be 0.27 cmH2O, range 0.14-0.61 cmH2O. During osmotic swelling Pin increased, in a non-linear fashion, to a value of 4.11 cmH2O, range 2.61-8.91 cmH2O, with increases in cell volume (Vc) of 24 +/- 3% (SE). This technique may be of use in the study of cellular mechanics.

Animals↗
PubMed1979

Measurement of the distensibility of the parabronchi in duck lungs.

Air flow resistance in the parabronchial lung of the duck was measured at various pressure differences between the lung and the body surface (Prs) using a body plethysmograph. One lung of the anesthetized animal was ventilated at a steady flow rate, from trachea, through the parabronchial lung, and out via a cannula in the caudal thoracic air sac (Tr leads to CS flow), or vice versa (CS leads to Tr flow), all flow being directed over the parabronchi (Pb) by blocking the main bronchus between the medioventral (MV) and mediodorsal secondary bronchi (MD). Pressure differences were measured between MV and MD (Ptot), and between the clavicular air sac and MD giving the pressure drop along the parabronchial tubes (PPb). The pressure drop along MV, PVb, was derived as Ptot-PPb. Air flow resistances, Rtot, RPb, RVb, were calculated from the ratio of the corresponding pressure difference to the flow rate. Results show: (1) All resistances decreased with increasing distending pressure (Prs) from -20 to +20 cm H2O this change being most pronounced around Prs = 0; (2) The flow resistance of these structures depended on the flow direction, being smaller with Tr leads to CS flow during distension than in the opposite direction; (3) Arterial blood gases did not significantly change with varying distending pressure, suggesting unimpaired gas exchange even when the lung is significantly compressed. The results indicate that the parabronchi and the secondary bronchi of the duck lung have a finite compliance but that changes in intrapulmonary pressure, compression of the lung, do not result in significant collapse of the air capillaries with ensuing impairment of gas exchange.

Airway Resistance↗
PubMed1979

The interaction between the diaphragm, intercostal/accessory muscles of inspiration and the rib cage.

During Mueller maneuvers (MM), the volume change of rib cage, delta Vrc, and abdomen, delta Vab, are equal and opposite. Thus delta Vrc = -delta Vab. Substituting delta Prc.Crc for delta Vrc and delta Pab.Cab for delta Vab yields: delta Prc = - delta Pab.Cab/Crc, where delta Prc, delta Pab, Crc and Cab are applied pressures and compliances of rib cage and abdomen respectively. MM performed solely with the diaphragm permits calculations of Prc in terms of observed changes in Pab and pleural pressure, Ppl. Three trained subjects performed MM with no evidence of inspiratory intercostal or abdominal muscle contraction. During the diaphragmatic MM delta Pab was positive and delta Prc negative. The magnitude of delta Prc/delta Pab was 2-6 times greater than that of delta Ppl/delta Pab. We conclude that neither Pab nor Ppl by themselves displace the relaxed rib cage during Mueller maneuvers. A model in which the diaphragm acts both in parallel and in series with the rib cage, and in which Prc is the sum of Pab and a pressure lying between Pab and Ppl explains these results as well as the hypothesis that Pab displaces the relaxed rib cage during quiet breathing.

Diaphragm↗
PubMed1979

A mathematical and graphical analysis of inspiratory muscle action.

In this paper a mathematical and graphical analysis is presented for the action of the diaphragm and the intercostal/accessory muscles of inspiration, in terms of the pressure developed, the volumes displaced and the work performed by each set of muscles. An analogous model is described which behaves according to the analysis. The critical variable by which the action of the diaphragm and intercostal/accessory muscles can be measured is the change in abdominal pressure Pab. When delta Pab = 0 it is assumed that the diaphragm has contracted isometrically and is acting as a fixator preventing an expiratory displacement of the abdomen. When delta Pab greater than 0 the diaphragm shortens and acts as an agonist. When delta Pab less than 0 the diaphragm lengthens as it contracts, performs negative work and the abdomen is displaced in an expiratory direction. For a given change in lung volume, as delta Pab diminishes, there is progressive recruitment of intercostal/accessory muscles and a progressive increase in the work of breathing over and above that required to produce the same change in lung volume by contraction of the diaphragm alone. For values of delta Pab greater than 0 the sum of diaphragm and intercostal/accessory muscle work is less than the total work, because of an increase in the elastic energy stored in the rib cage. For Pab less than 0 there is a decrease in the elastic energy stored in the rib cage leading to a marked increase in work performed and pressures developed by the intercostal/accessory muscles.

Abdomen↗
PubMed1979

Influence of immersion to the neck in water on airway closure and distribution of perfusion in man.

We measured closing volume (CV), expiratory reserve volume (ERV) regional distribution of lung volume (Vr) and perfusion in 7 normal subjects in air and during immersion to the neck in water. In four subjects immersion resulted in a CV greater than ERV and the normal perfusion distribution became inverted. In the other subjects, ERV remained larger than CV and perfusion distribution during immersion was uniform, not inverted. In 5 subjects closing volume increased and in 3 of them, the ratio of apical/basal Vr increased significantly during immersion. One subject had nomeasurable CV and in the other it was not measured. The data suggest: (1) that when CV is greater than ERV during immersion there is an inversion of the normal perfusion distribution, caused by hypoxia and/or an increase in mean alveolar pressure in the alveoli beyond the closed airways, and (2) that an increase in pleural pressure gradient during immersion may contribute to the increase in C.V.

Adolescent↗
PubMed1979

Electromyogram pattern of diaphragmatic fatigue.

We studied the effect of breathing at various levels of transdiaphragmatic pressure (Pdi) on the EMG power spectrum of the diaphragm. The diaphragmatic EMG was measured simultaneously with a bipolar esophageal electrode (EE) and surface electrode (SE) placed on the ventral portion of the sixth and seventh intercostal spaces in five normal subjects breathing at functional residual capacity (FRC) against an inspiratory resistance. During each fatigue run the subjects generated a Pdi, with each inspiration, that was 25, 50, or 75% of maximum Pdi (Pdimax) for a period up to 15 min. During runs at 50 and 75% of the Pdimax, which are known to produce fatigue, we found for both EE and SE a progressive increase in the amplitude of the low-frequency (L = 20-46.7 Hz) and a decrease in the high-frequency (H = 150-350 Hz) component of the EMG. These changes were not seen at 25% of Pdimax. The diaphragmatic H/L ratio was independent of Pdi when the diaphragm was not fatigued. H/L fell while the diaphragm performed fatiguing work and this was more rapid at higher Pdi's. It was thus concluded that frequency spectrum analysis of the EMG can detect diaphragmatic fatigue reliably, prior to the time when the diaphragm fails as a pressure generator.

Diaphragm↗