Weight loss, weakness and an abnormal roentgenogram of the chest in a 72-year-old woman.
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Biomedical subjects
Publications and source records attributed to P T Macklem.
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The critical value of the rate of energy consumption of the inspiratory muscles above which fatigue occurs appears in some instances to be predictable from the relationship between energy demands and energy supplies rather than from the percentage of fatigue-resistant fibres in the inspiratory muscles. When this is the case the critical value of the external power produced by the inspiratory muscles is given by the product of muscular efficiency and the rate at which energy is supplied. Efficiency is reduced by hyperinflation and recruitment of the intercostal and accessory muscles of inspiration. The rate at which energy is supplied is decreased in states characterized by low cardiac output. The condition of low cardiac output, combined with the high oxygen cost of breathing against fatiguing loads, may be lethal in cardiogenic shock. Although the immediate cause of fatigue may not be related to reduced energy supplies, clinically useful predictions of conditions predisposing to fatigue result from an understanding of factors determining the balance between the energy demands and supplies of the inspiratory muscles. These predictions aid in the diagnosis of inspiratory muscle fatigue and have important therapeutic implications.
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The effects on exercise performance of physiotherapy (PT) (8 patients) were compared with those of inspiratory muscle training (IMT) (9 patients) in severe chronic airflow limitation. Exercise performance was measured by 3 tests: the distance walked in 12 min, peak oxygen uptake on a progressive multistage exercise test, and endurance time at two thirds of maximal power output. Measurements were repeated after a 1-month control period during which no change was observed apart from an increase in the distance walked in 12 min in the PT group. The PT patients then performed graded exercise in a physiotherapy program 3 times weekly, whereas the IMT patients trained for 30 min daily, inspiring against a resistance. Measurements were repeated after 1 and 2 months of training. Physiotherapy was associated with insignificant increases in exercise performance, whereas IMT produced both an increase in endurance time and in the distance walked in 12 min. We concluded that a simple at-home training program of inspiratory muscles was more effective than this particular physiotherapy program in improving exercise performance of some patients with severe chronic airflow limitation.
Using a simple, inexpensive, at-home program, 12 patients with moderate-to-severe chronic air flow limitation trained their inspiratory muscles. All showed increased inspiratory muscle endurance with no change in inspiratory muscle strength. Seven of the twelve patients increased their endurance time for submaximal exercise beyond the 90% confidence limits determined by 2 pretraining tests (i.e., a more than 40% increase in endurance time). The same group of 7 patients increased the maximal power output (p less than 0.005) and peak oxygen uptake (p less than 0.05) on a progressive exercise test after 2 months of training and increased the distance walked in 12 min after both 1 (p less than 0.005) and 2 (p less than 0.005) months of training. In 6 of the 7 patients in this group, the pretraining submaximal exercise tests were accompanied by electromyographic changes heralding inspiratory muscle fatigue. Their increased endurance time post-training was associated with a delay or absence of these changes. In the other group of 5 patients, who showed no change in exercise performance with training, electromyographic changes heralding inspiratory muscle fatigue were never observed in submaximal exercise tests. We concluded that although the endurance of the inspiratory muscles of patients with chronic airflow limitation is increased, specific training of the inspiratory muscles is usually associated with improved exercise performance only in those who demonstrate electromyographic changes heralding inspiratory muscle fatigue during exercise.
We recorded an index of breath sound intensity (Ib) and the transmission of white noise (Tn) over four lung regions between apex and base in eight subjects with emphysema. The Ib and Tn were recorded over the whole range of lung volume from residual volume to total lung capacity. Each value was expressed as a fraction of the value recorded over the apical region with the help of an analog divider. The ratio of Ib to Tn was computed to correct for differences in Ib due to differences in transmission of sound. The ratio of Ib and Tn was computed to correct for differences in Ib due to differences in transmission of sound. The ratio of Ib to Tn was also expressed as a fraction of the value recorded over the apex. Both Ib and Tn had definite patterns in subjects with emphysema but varied considerably from breath to breath. The Ib and Tn were more reproducible in normal subjects. The magnitude and the sequence of Ib, Tn, and Ib/Tn were also different in subjects with emphysema and normal subjects. The ratio of Ib to Tn is an index of sound production in both normal subjects and subjects with emphysema. We conclude that both production and transmission of breath sounds vary from breath to breath in patients with emphysema. There are areas of both increased and decreased production and transmission of sound. If regional breath sound production (Ib/Tn) is related to regional ventilation in persons with emphysema as in normal subjects, these findings further suggest that regional ventilation varies from breath to breath and is also altered drastically from the normal pattern, leading to a severe ventilation and perfusion inequality so characteristic of emphysematous lungs.
The effects of hypoxemia on inspiratory muscle fatigue were assessed in 4 normal subjects. They breathed to exhaustion through high inspiratory resistances producing an inspiratory mouth pressure (Pm) of about 80% of maximal mouth pressure. The endurance time (tlim) during hypoxia (13% O2) was found to be shorter than that while breathing room air at equal inspiratory mouth pressures. Endurance time during hypoxia was also compared with that while breathing room air at equal rates of energy consumption (C), assuming that C is proportional to: Formula: (See Text). At these equal rates, endurance time during hypoxia still remained shorter than that during normoxia. Fatigue was also assessed by measuring the electromyographic power spectrum of the diaphragm and the parasternal intercostals. The power spectrum shifted towards low frequencies during fatigue and a greater rate of shift was observed under hypoxic conditions. The rate of lactate production during hypoxemia was greater than that during normoxia; however, blood lactate concentrations at the end of the tests were similar under both conditions. It was concluded that respiratory muscles, working against high inspiratory resistances, fall as pressure generators sooner during low oxygen breathing. The effect of low oxygen breathing on inspiratory muscle fatigue resulted in a shorter endurance time, a faster rate in the shift of the electromyographic power spectrum, and a greater rate of increase in blood lactate concentrations.
The authors define small airways disease and then describe its anatomical characteristics. In the early stage bronchial inflammation is found along with arterial lesions. As the disease develops, there are multiple bronchial and vascular alterations, often accompanied by emphysema. The few existing studies of the morphology/lung function test correlation show a relationship between small airways disease and abnormal respiratory function tests. One of the aims was to find the most sensitive and specific tests using the smoker as a model. However, as only 25% of smokers develop clinical abnormalities, the main problem is probably not early screening, but finding the parameter with the highest prognostic value. This should be the FEVI, measured at about age 40. At a younger age, the information is still too incomplete. More studies are needed to justify early screening. Finally, the authors discuss the procedure to be followed when abnormalities are detected, and its possible consequences on lung function and behaviour.
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The composite vagus nerve was stimulated during intravenous infusion of 5-hydroxytryptamine in cats subjected to pharmacologic autonomic blockade with atropine, propranolol, and phentolamine. Bronchial caliber, as assessed by changes in pulmonary resistance, demonstrated a marked dilatation, and dilatation could still be demonstrated after preliminary treatment with reserpine. By stimulating the component branches of the vagus nerve, it was determined that the parasympathetic branch is responsible for this phenomenon.
The diaphragmatic electromyogram was used to detect fatigue of the diaphragm in six chronic quadriplegics while they breathed for 10 minutes against a variety of inspiratory resistances. The maximum static inspiratory mouth pressure was measured at functional residual capacity (Pmmax) and from the electromyogram the critical inspiratory mouth pressure that developed in each inspiration (Pmcrit) below which electromyographic changes of diaphragmatic fatigue do not develop was estimated. The measurements were repeated after 8, 12 and 16 weeks of inspiratory muscle training consisting of inspiring for a period of 30 minutes daily, six days a week, against a resistance just sufficient to produce the electromyographic changes of fatigue. A significant and progressive increase in Pmmax and Pmcrit was found during the training. It was concluded that (1) quadriplegics are predisposed to the development of inspiratory muscle fatigue due to reduced muscle strength and reduction in endurance, and (2) in these patients inspiratory muscle training increases both strength and endurance, and protects against fatigue.
In nine normal subjects we measured pulmonary pressure-flow curves by ensemble averaging over 20 breaths and solving the equation P = K'V alpha where P is flow-resistive pressure, K' is slope, 5 V is flow, and alpha is curvilinearity. The study was performed at four lung volumes from 37 to 73% of total lung capacity, with the subjects breathing air or HeO2. K' was lower at every lung volume during HeO2 breathing, whereas the exponent alpha was uninfluenced by either lung volume or HeO2 breathing. Although alpha increased with flow rate, comparison of air and HeO2 curves revealed that alpha was not uniquely related to Reynolds' number. Furthermore there was no correlation between curvilinearity and the density dependence of K'. These observations are inconsistent with the general equation P = KV alpha rho alpha-1 mu 2-alpha, where K is a constant related to airway geometry, rho is density and mu is viscosity. (Wood et al., J. Appl. Physiol. 41: 234-244, 1976). The reasons for this discrepancy are unclear, but do not appear to be related to effects of oscillatory flow because alpha was similar from 20 to 90 breaths/min in four subjects. We conclude that the curvilinearity of pulmonary pressure-flow curves is related to flow but independent of gas density and is not explicable solely on the basis of Reynolds' number.
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Most equations proposed to describe pulmonary pressure-flow relationships are inadequate because the "constants" that contain the airway geometry are not, in fact, constant but vary as the distribution of Reynold's number Re varies with flow or gas density. However, even when the normalized pressure drop is plotted against Re (Moody diagram), different relationships are found for different gas mixtures. Thus the normalized pressure drop is a function of one or more variables in addition to Re. As long as this variable or variables remain unknown, the pulmonary pressure-flow relationships will remain paradoxical.
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.
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.
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.