Respiratory Muscles: Work and Force Development It seems likely that the ventilatory capacity-demand balance is sensed by monitoring respiratory effort rather than blood gases. While abnormal blood gases do not correlate particularly well with dyspnea, increased relative or absolute work of breathing or respiratory effort does. In absolute terms, most dyspneic patients work harder to breathe because of abnormalities in airways resistance or in lung or chest wall compliance. However, the notion that absolute work of breathing is a prominent factor in dyspnea fails to explain the occurrence of dyspnea in partially paralyzed individuals with normal lungs, in whom the work of breathing is, if anything reduced. This suggests that relative work of breathing, that is, ventilatory work normalized for maximal work, may be a more useful concept. A number of instances can be found in which dyspnea and respiratory work can be dissociated. For example, in the case of paralyzed respirator patients, already alluded to, in whom a reduction of the respirator setting led to increased dyspnea, there was probably little or no increase in respiratory work by the patient compared to the hypercapnic challenge, yet dyspnea increased." Perhaps even more convincing is the common experience that a breath hold, which ultimately leads to an intense dyspnea like sensation at break point, involves no true inspiratory work because no gas is being moved. Some other means of translating the ventilatory capacity-demand imbalance into the subjective sensation of dyspnea must exist. If increased absolute or relative respiratory work does not offer a satisfactory explanation for dyspnea, perhaps the force or pressure developed in the attempt to breathe provides a better explanation. Indeed, intrapleural or trans-pulmonary pressures, expressed either in absolute terms or as a proportion of maximum developed pressures, seem to account convincingly for dyspnea thresholds in health and disease, within patients at rest or exercising, and following oxygen administration. Marshall, Stone, and Christie, for example, showed that during increasing muscular exercise, the plateau for ventilation-a presumed objective counterpart of dyspnea-was better correlated with developed intrapleural pressure than with work of breathing. This relationship held true for normal subjects and for patients with mitral stenosis or emphysema. The addition of an external resistance tended to decrease exercise tolerance and was associated with a decrease in respiratory work but with an increase in the intrapleural pressure at which ventilation plateaued. Some investigators have also found a convincing relationship between the development of dyspnea and the tidal change in trans-pulmonary pressure, the rate of change in pressure, or the relative pressure, that is, absolute pressures expressed as a percentage of maximum voluntary pressures. Just as respiratory force and pressure development may be important in the development of dyspnea, they may also be major determinants of the normal breathing pattern. Otis, Fenn, and Rahn long ago pointed out that normal subjects choose a resting respiratory pattern that requires the least expenditure of effort. Thus, the tidal volume selected is large enough to efficiently ventilate alveoli but small enough to avoid the penalties associated with elastic work, which become marked at high tidal volumes. Concomitantly, breathing frequency is selected to keep airflow low enough to minimize the resistive work penalties associated with high airflows. More detailed studies of breathing patterns in a number of experimental and pathological conditions subsequently confirmed this finding but suggested that the selection of respiratory pattern is linked more closely to the reduction of developed forces or pressures than to the reduction of work. It was found that elastic loads, which unduly increase the pressures required to generate normal tidal volumes, result in rapid, shallow breathing, whereas resistive loads, which increase the pressures required to generate airflow, result in slower, deeper breathing with lower flow rates. Thus, equivalent increases in respiratory work lead to different changes in respiratory pattern that have the effect in each case of minimizing the forces or pressures required for ventilation. Respiratory pressures may be used by healthy people as a subconscious error signal to optimize respiratory patterns, and it may be that dyspnea arises when this error signal has become so large as to intrude on consciousness. Where does the actual sensation of increased pulmonary pressure arise? Much evidence favors respiratory muscles as an important site. There is a growing opinion that, in general, muscles are far more important than joints in sensing motion, position, and force or effort. The diaphragm in particular, seems to be involved: increased activity on the diaphragmatic electromyogram (EMG) is closely correlated with the occurrence of dyspnea, and spinal block, which leaves the diaphragm unaffected, has little effect on the duration of breath hold or the sensation associated with it. In chronic obstructive pulmonary disease, dyspnea is increased in the supine position but is promptly relieved with mechanical respiratory assist. Both effects correlate with changes on the diaphragmatic EMG, which is increased in the supine position and suppressed by ventilatory assist. Furthermore, as mentioned above, in paralysis with curare, which, unlike spinal block, does paralyze the diaphragm, the break point sensation during breath hold was virtually abolished. It must be pointed out, however, that these results are at variance with the common complaint of dyspnea in patients with disease-related paralysis or muscle weakness. Perhaps the difference lies in the more uniform effects of curare. If disease-related paralysis leaves some muscle units able to respond and develop force while others cannot, the increased activity of the functional or partly functional units could account for the development of dyspnea. That dyspnea occurs in patients with paralysis or muscle weakness indicates that absolute force or pressure development, which is reduced in such patients, cannot by themselves account for the sensation. Perhaps, then, the precipitating factor is relative, as opposed to absolute, pressure. Although there is no clear proof that such relative quantities are indeed responsible, nor is the mechanism of their detection certain, such considerations have led Campbell and Howell to propose an intriguing and plausible theory-that appropriateness of change in respiratory muscle length and tension is critical in the pathogenesis of dyspnea. The notion here is that individuals are able to appreciate the relationship between an applied effort and the resulting response. A person quickly becomes aware that a well-defined effort will be sufficient to lift a familiar object such as a baseball; but if the baseball contained a concealed lead core, greatly increasing its weight, the person would be startled by the unexpected effort required to lift it. Similarly, at high altitude, individuals unaccustomed to such altitudes are surprised by the increased shortness of breath (dyspnea) associated with commonplace activities. In both cases, the sensation arises from the apparent inappropriateness of the increased effort required to carry out familiar tasks. Specifically, in the case of respiratory and other muscles this sensation might arise through monitoring of developed muscle tension and the resulting change in muscle length, that is, length–tension inappropriateness. There are two types of sensors that could provide information about such a relationship. The Golgi tendon organ is capable of providing a measure of muscle tension, and the muscle spindle can monitor muscle length. The spindle is a complex sensor containing at least two muscle systems, intra- and extrafusal, and at least two motor innervations, gamma and alpha, as well as intrafusal stretch receptors. It is capable of sensing changes in relative tension because its intrinsic muscles respond to intensity of alpha Moto neuron transmission to the parent muscle, which adjusts the length of the spindle. This, in turn, alters the tension sensed by the spindle. Thus, the spindle can serve as a comparator capable of determining whether a change in muscle length corresponds to that called for by the CNS. These concepts are appealing in that they unify several diverse causes of dyspnea. In cases of lung dysfunction, where disproportionately high muscle tension is required to develop the high pressures needed to maintain normal ventilation, spindles may produce a signal proportional to the inappropriateness of the length-tension relationship. Similarly, in diseases with muscle weakness or paralysis, the muscle spindle may sense a disparity between the intensity of the command it receives and the reduced extent of muscle shortening that results. Clearly, many of the conditions that precipitate dyspnea may also lead to respiratory muscle fatigue, and it is possible that the two are interrelated in some fashion. Fatigue could contribute to the sensation of dyspnea. Alternatively, dyspnea might lead either to changes in respiratory pattern or to limitations in physical activity that would prevent or postpone the development of muscle fatigue. Indeed, recent studies suggest that, in exercise, patients with chronic obstructive pulmonary disease select respiratory patterns that produce relatively high Trans diaphragmatic pressures of short duration that lead to dyspnea but little or no fatigue. In contrast, imposed changes in breathing pattern designed to prolong inspiratory time with lower pressures but greater pressure-time products lead to diaphragmatic fatigue but less dyspnea.