The control of cell volume: frog eggs face an extreme challenge.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
P T Macklem
Publications and source records attributed to P T Macklem.
Pleural pressure from abdominal to pulmonary rib cage: sweep of the lung border.
Pleural pressure was measured by a capsule placed in the superior part of right 8th or 9th intercostal space of dogs in left lateral posture. Transit of lung border was observed through endothoracic fascia at sides of the capsule. During inspiration the capsule membrane faced sequentially: diaphragm, lung border, lung; vice versa during expiration. Pressure on the diaphragm at end expiration was -5.3 +/- 0.5 cm H2O, reflecting outward recoil of the rib cage. At transit of lung border during inspiration (bor. I) a marked negative pressure spike occurred; a smaller spike occurred at expiratory transit (bor. E). These spikes should reflect pleural liquid pressure at lung border. At bor. I lung volume and radial displacement of rib 9 or 10 were greater during active than passive ventilation, whereas at bor. E they were similar under both conditions. Hence, during spontaneous inspiration displacement of lung border lags behind lung and rib expansion. Speed of lung border (assessed from duration of negative spike) ranged from 0.8 to 2.3 cm/sec during spontaneous breathing. On average it was similar at bor. I and bor. E, while air flow was greater at bor. I.
Animals↗
Lung border sweep upon phrenic stimulation: dynamic fall in pleural liquid pressure.
Pleural pressure was measured by a capsule in 9th or 10th intercostal space (ics) of dogs during tetanic stimulation of phrenic nerves (PS). When lung border passed under capsule (bor.I) a marked negative spike occurred, reflecting pleural liquid pressure (Pliq). In 9th ics spike was briefer than during spontaneous breathing (SB), speed of lung border being 4.6 times greater. During PS spike was greater and longer in 10th than in 9th ics, lung volume at bor.I being 228 ml greater. Lung volume at bor.I was smaller during PS than passive inflation because of chest wall deformation. Dynamic fall in Pliq at bor.I has been estimated about 4 cm H2O during SB, and at least 12 and 16 cm H2O (in 9th and 10th ics, respectively) during PS. Dynamic fall in Pliq seems essentially a viscous loss: it increased with thinning of pleural liquid (increase in lung volume), and with speed and displacement of lung border. Results suggest that at ordinary lung volume viscous loss of pleural liquid in this region is about 2 cm H2O per cm displacement at a speed of 1 cm/sec.
Animals↗
Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats.
We examined the effects of elastase-induced emphysema on lung volumes, pulmonary mechanics, and airway responses to inhaled methacholine (MCh) of nine male Brown Norway rats. Measurements were made before and weekly for 4 wk after elastase in five rats. In four rats measurements were made before and at 3 wk after elastase; in these same animals the effects of changes in end-expiratory lung volume on the airway responses to MCh were evaluated before and after elastase. Airway responses were determined from peak pulmonary resistance (RL) calculated after 30-s aerosolizations of saline and doubling concentrations of MCh from 1 to 64 mg/ml. Porcine pancreatic elastase (1 IU/g) was administered intratracheally. Before elastase RL rose from 0.20 +/- 0.02 cmH2O.ml-1.s (mean +/- SE; n = 9) to 0.57 +/- 0.06 after MCh (64 mg/ml). A plateau was observed in the concentration-response curve. Static compliance and the maximum increase in RL (delta RL64) were significantly correlated (r = 0.799, P less than 0.01). Three weeks after elastase the maximal airway response to MCh was enhanced and no plateau was observed; delta RL64 was 0.78 +/- 0.07 cmH2O.ml-1.s, significantly higher than control delta RL64 (0.36 +/- 0.7, P less than 0.05). Before elastase, increase of end-expiratory lung volume to functional residual capacity + 1.56 ml (+/- 0.08 ml) significantly reduced RL at 64 mg MCh/ml from 0.62 +/- 0.05 cmH2O.ml-1.s to 0.50 +/- 0.03, P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway Resistance↗
Negative pressure ventilation. Effects on ventilation during sleep in normal subjects.
Negative pressure ventilation (NPV) is used for ventilatory support of patients with respiratory failure due to neuromuscular disorders and thoracic deformities, and to provide ventilatory muscle rest for patients with severe chronic airflow limitation. To determine whether NPV would result in episodes of upper airway obstruction during sleep, we studied five normal subjects on two consecutive nights with the first night serving as a control and NPV being administered on the second night. Ventilators were adjusted so as to reduce the peak phasic diaphragm electromyogram signal by at least 50 percent. All subjects demonstrated an increase in the total number of apneas + hypopneas per hour on NPV control nights. Although differences were not significant, there was a tendency to develop decreased sleep efficiency, sleep fragmentation and altered sleep architecture with NPV. We conclude that nocturnal NPV can induce sleep apneas and impair sleep quality in normal subjects.
Adult↗
Risk factors and prevention strategies for asthma.
Explore the source record for details and available documents.
Allergens↗
Mechanical factors determining maximum bronchoconstriction.
The principal feature which distinguishes asthmatics from normal subjects is that their airways constrict excessively to stimuli, to the extent that airway narrowing exceeds the maximum degree of bronchoconstriction which occurs in normal subjects. The load against which bronchial smooth muscle contracts is a very important determinant of the degree of airway narrowing. The elastic properties of the airway wall itself and the interdependence between the airways and the surrounding parenchyma are the elastic load which bronchial smooth muscle has to overcome to narrow the airway. The most likely explanation of a decreased load in asthma is oedema of the airway wall, because it may unlink the interdependence between the airway and the surrounding parenchyma.
Asthma↗
Optimization of respiratory muscle relaxation during mechanical ventilation.
The authors calculated the active work of inspiration (Wp) and the inspiratory muscle pressure-time product (integral of Pmus.dt) in seven patients undergoing mechanical ventilation (MV). This was done by comparing the areas under the inflation pressure-volume and inflation pressure-time curves generated when the patient was contributing to the work of ventilation with those following sedation, when inspiratory muscle activity was absent (defined as absence of diaphragmatic EMG activity and of palpable accessory muscle contraction). Inspiratory muscle inactivity could be predicted by the observation of a smooth rise in inflation pressure that was highly reproducible from breath to breath. Relaxation was present without sedation during MV in the control mode with inspiratory flow rates above 65 1/min. In the assist mode (AMV), both Wp and integral of Pmus.dt were significantly (P less than 0.05) greater than in the control (CMV) mode. Reducing trigger sensitivity during AMV further increased Wp and integral of Pmus.dt (P less than 0.05). During AMV and CMV Wp and integral of Pmus.dt decreased with increasing rate of inspiratory flow delivered by the ventilator. With AMV at low trigger sensitivity and low flow rates, Wp approached 65% of the total inspiratory work. The authors conclude that inspiratory muscle activity can be substantial during MV, particularly during AMV at low trigger sensitivity and flow. Monitoring of inflation pressure is a simple means of determining the degree of inspiratory muscle rest during MV.
Humans↗
Effect of lung volume on interrupter resistance in cats challenged with methacholine.
To examine the effects of changes in lung volume on the magnitude of maximal bronchoconstriction, seven anesthetized, paralyzed, tracheostomized cats were challenged with aerosolized methacholine (MCh) and respiratory system resistance (Rss) was measured at different lung volumes using the interrupter technique. Analysis of the pressure changes following end-inspiratory interruptions allowed us to partition Rss into two quantities with the units of resistance, one (Rinit) corresponding to the resistance of the airways and the other (Rdif) reflecting the viscoelastic properties of the tissues of the respiratory system as well as gas redistribution following interruption of flow. Rinit and Rdif were used to construct concentration-response curves to MCh. Lung volume was increased by the application of 5, 10, and 15 cmH2O of positive end-expiratory pressure. The curve for Rinit reached a plateau in all cats, demonstrating a limit to the degree of MCh-induced bronchoconstriction. The mean value of Rinit (cmH2O.ml-1.s) for the group under control conditions was 0.011 and rose to 0.058 after maximal bronchoconstriction; the volume at which the flow was interrupted was 11.5 +/- 0.5 (SE) ml/kg above functional residual capacity (FRC). It then fell progressively to 0.029 at 21.2 +/- 0.8 ml/kg above FRC, 0.007 at 35.9 +/- 1.3 ml/kg above FRC, and 0.005 at 52.0 +/- 1.8 ml/kg above FRC. Cutting either the sympathetic or parasympathetic branches of the vagi had no significant effect on the lung volume-induced changes in MCh-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway Resistance↗
Pleural pressure between diaphragm and rib cage during inspiratory muscle activity.
We measured the changes in pleural surface pressure (delta Ppl) in the area of apposition of the rib cage to the diaphragm (Aap) in anesthetized dogs during spontaneous breathing, inspiratory efforts after airway occlusion at functional residual capacity, and phrenic stimulation. Intact dogs were in supine or lateral posture; partially eviscerated dogs were in lateral posture. delta Ppl,ap often differed significantly from changes in abdominal pressure (delta Pab); sometimes they differed in sign (except during phrenic stimulation). Changes in transdiaphragmatic pressure in Aap (delta Pdi,ap) could be positive or negative and were less in eviscerated than in intact dogs. delta Pdi,ap could differ in sign among respiratory maneuvers and over different parts of Aap. Hence average delta Pdi,ap should be closer to zero than delta Pdi,ap at a given site. Since delta Ppl,ap = delta Prc,ap, where Prc,ap represents rib cage pressure in Aap, delta Pdi,ap = delta Pab - delta Prc,ap. Hence, considering that delta Pab and delta Prc depend on different factors, delta Pdi,ap may differ from zero. This pressure difference seems related to the interaction between two semisolid structures (contracted diaphragm and rib cage in Aap) constrained to the same shape and position.
Animals↗
Transdiaphragmatic pressure and rib motion in area of apposition during paralysis.
Changes in pleural surface pressure in area of apposition of diaphragm to rib cage (delta Ppl,ap), changes in abdominal pressure (delta Pab), and redial displacement of the 11th rib have been recorded in anesthetized, paralyzed dogs during lung inflation or deflation. Above functional residual capacity (FRC) changes in transdiaphragmatic pressure in area of apposition (delta Pdi,ap) were essentially nil in intact (INT) dogs either in lateral or supine posture, and in partially eviscerated (EVS) dogs in lateral posture, either in the 10th or 11th intercostal space. Below FRC delta Pdi,ap could be positive (INT lateral and EVS), nil (EVS), or negative (INT supine and EVS); it could be different in the 10th and 11th intercostal spaces. Hence, with stretched (like with contracted) diaphragm, delta Ppl,ap measured at one site often differs from delta Pab and is not representative of average pressure acting on area of apposition. With volume increase above FRC, the 11th rib moved slightly in and then out in EVS and linearly out in INT. With volume decrease below FRC it moved out progressively in EVS, and it moved in and eventually reversed in INT. In paralyzed dogs in lateral posture the factor having the greatest influence on displacement of the abdominal rib cage is Pab. Mechanical linkage with pulmonary rib cage becomes relevant at large volume, whereas insertional traction of diaphragm becomes relevant at low volume.
Animals↗
Respiratory sensation and pattern of respiratory muscle activation during diaphragm fatigue.
We have examined the relationship between respiratory effort sensation (modified Borg scale) and amplitude of the integrated surface electromyogram of the diaphragm (Edi, esophageal electrode), rib cage muscles (Erc), and sternomastoid muscle (Esm) during the development of diaphragm fatigue in five normal subjects. Three conditions were studied: run A: transdiaphragmatic pressure (Pdi), 65% Pdimax; esophageal pressure (Pes), 60% Pesmax; run B: Pdi, 50% Pdimax; Pes, 60% Pesmax; and run C: Pdi, 50% Pdimax; Pes, 20% Pesmax. During all runs there was a progressive rise in sensation, which was greater in runs A and B than in run C (P less than 0.05, analysis of variance). There was no difference between runs A and B. At the end of run C subjects did not report a maximal Borg score despite their inability to generate the target Pdi. The increase in sensory score with fatigue correlated highly with Esm/Esmmax and with Erc/Ercmax. There was no correlation between sensory score and Edi/Edimax. We conclude that the increase in respiratory effort sensation that accompanies diaphragm fatigue is not due to perception of increased diaphragmatic activation. It may reflect increased overall respiratory motor output not directed to the diaphragm.
Adult↗
Clinical assessment of the respiratory muscles.
Explore the source record for details and available documents.
Humans↗
Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans.
We examined the effects of lung volume on the bronchoconstriction induced by inhaled aerosolized methacholine (MCh) in seven normal subjects. We constructed dose-response curves to MCh, using measurements of inspiratory pulmonary resistance (RL) during tidal breathing at functional residual capacity (FRC) and after a change in end-expiratory lung volume (EEV) to either FRC -0.5 liter (n = 5) or FRC +0.5 liter (n = 2). Aerosols of MCh were generated using a nebulizer with an output of 0.12 ml/min and administered for 2 min in progressively doubling concentrations from 1 to 256 mg/ml. After MCh, RL rose from a base-line value of 2.1 +/- 0.3 cmH2O. 1-1 X s (mean +/- SE; n = 7) to a maximum of 13.9 +/- 1.8. In five of the seven subjects a plateau response to MCh was obtained at FRC. There was no correlation between the concentration of MCh required to double RL and the maximum value of RL. The dose-response relationship to MCh was markedly altered by changing lung volume. The bronchoconstrictor response was enhanced at FRC - 0.5 liter; RL reached a maximum of 39.0 +/- 4.0 cmH2O X 1-1 X s. Conversely, at FRC + 0.5 liter the maximum value of RL was reduced in both subjects from 8.2 and 16.6 to 6.0 and 7.7 cmH2O X 1-1 X s, respectively. We conclude that lung volume is a major determinant of the bronchoconstrictor response to MCh in normal subjects. We suggest that changes in lung volume act to alter the forces of interdependence between airways and parenchyma that oppose airway smooth muscle contraction.
Adult↗
Effect of hyperinflation and equalization of abdominal pressure on diaphragmatic action.
We tested the hypothesis that the mechanical arrangement of costal (COS) and crural (CRU) diaphragms can be changed from parallel to series when direct or indirect transmission of tension occurs. Ratio of rib cage to abdominal displacement (RC/AB) resulting from separate COS and CRU stimulations were used to measure RC expanding action. Hyperinflation in six dogs caused RC/AB with COS and CRU stimulations to change progressively from 0.53 +/- 0.07 (SE) and 0.03 +/- 0.05 at functional residual capacity (FRC) to -0.48 +/- 0.08 and -0.46 +/- 0.05 at 68% inspiratory capacity, respectively. Liquid substitution of abdominal contents in six other dogs equalized abdominal pressure swings (delta Pab), without changing chest wall elastic properties or geometry, or costal RC/AB (0.35 +/- 0.07 before and 0.33 +/- 0.06 after) but caused crural RC/AB to change from 0.01 +/- 0.05 to 0.31 +/- 0.01. We conclude that hyperinflation changes fiber orientation, allowing direct transmission of tension between COS and CRU, which become linked mechanically in series (the diaphragm acts as a unit with RC deflating action); and equalization of delta Pab causes indirect transmission of tension between COS and CRU, which become linked in series (the diaphragm acts as a unit with RC inflating action).
Abdomen↗
Airway responses to aerosolized methacholine in the cat. Effects of partial or complete vagosympathectomy.
To explore the role of airway innervation as a determinant of airway responsiveness to inhaled cholinergic agonists, we studied the effects of partial or complete section of the cervical vagosympathetic trunk on the magnitude of methacholine-induced bronchoconstriction in the chloralose-urethane-anesthetized, mechanically ventilated cat. An initial concentration-response curve to methacholine was constructed to identify the concentration required to cause a twofold to threefold rise in mean pulmonary resistance (RL). Using this concentration, 3 consecutive challenges (C1, C2, and C3) were then performed at 30-min intervals in 4 groups of cats. After a control challenge (C1), the parasympathetic (n = 9), sympathetic (n = 6), or both branches (n = 4) of the cervical vagosympathetic trunks were sectioned. Sham cats (n = 7) showed reproducible increases in RL (C1, delta RL = 15.1 +/- 2.7 cm H2O X 1(-1) X s; C2, delta RL = 15.7 +/- 3.0; C3, delta RL = 13.1 +/- 2.9; mean +/- 1 SE). After parasympathectomy there was an increase in responsiveness after C3 (C1, delta RL = 15.0 +/- 4.3; C2, delta RL = 16.4 +/- 6.4; C3, delta RL = 29.9 +/- 11.6; p less than 0.01). Sympathectomy and vagosympathectomy did not significantly alter responsiveness. The results suggest that vagally mediated inhibitory influences modulate the bronchial response to aerosolized methacholine in the cat.
Aerosols↗
Bronchial hyporesponsiveness.
It is argued that the dose-response curve for asthmatic patients is of a form that would be expected from the in vitro active force length relationship of bronchial smooth muscle if shortening at maximal isometric tension is quasi-isotonic. If this is the case, it may be more important to attempt to explain normal bronchial hyporesponsiveness, in particular whether bronchoconstriction is quasi-isotonic. In vivo response to inhalation depends on change in length of bronchial smooth muscle cells. Further studies should focus on factors influencing change in length rather than change in force.
Airway Resistance↗
(T)he(o)retical ideas of diaphragmatic action.
The diaphragm can be considered as 2 muscles, 1 which displaces both rib cage and abdomen in the inspiratory direction, and another which displaces only the abdomen. A theoretical analysis indicates that although the 2 parts are arranged as muscles mechanically in parallel, or as pumps pneumatically in series - and therefore the force and pressure developed by the diaphragm is the sum of the forces and pressures developed by each part - no anatomical site can be specified where a pressure can be measured to partition transdiaphragmatic pressure (Pdi) into its 2 components. However, a pneumatic analogue of the inspiratory muscles and the structures they displace allows for the construction of a pressure-balance equation between the rib cage and abdomen during a pure diaphragmatic Meuller maneuvre. This allows an expression which partitions Pdi in terms of the ratio of pleural to abdominal pressure changes, the ratio of abdominal to rib cage compliance, and the area of apposition of the costal fibres of the diaphragm to the rib cage. The first 2 are constants during pure diaphragmatic Meuller maneuvres. Published data for the 3 quantities suggest that the component of Pdi which acts to inflate the rib cage is only a small component of total Pdi.
Diaphragm↗