Modulation of Respiratory System by Limb Muscle Afferents in Intact and Injured Spinal Cord

Skeletal muscle is the largest organ in the body. Skeletal muscles are primarily characterized by their mechanical activity required for posture, movement, and breathing, which depends on muscle fiber contractions. However, skeletal muscle is not just a component in our locomotor system. Recent evidence has identified skeletal muscle as a secretory organ. We have suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects should be classified as "myokines." The muscle secretome consists of several hundred secreted peptides. This finding provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs such as adipose tissue, liver, pancreas, bones, and brain. In addition, several myokines exert their effects within the muscle itself. Many proteins produced by skeletal muscle are dependent upon contraction. Therefore, it is likely that myokines may contribute in the mediation of the health benefits of exercise. © 2013 American Physiological Society.

1. In anaesthetized and decerebrate cats isometric exercise of the hind limb muscles was elicited by stimulating the spinal ventral roots L7-S1. This caused a rise in arterial blood pressure, with small increases in heart rate and pulmonary ventilation. These changes were abolished by cutting the dorsal roots receiving afferents from the exercising muscle.2. When the triceps surae muscle was made to exercise by ventral root stimulation, occlusion of the femoral artery and vein through and beyond the period of exercise caused the blood pressure to remain raised until the occlusion was removed. The ventilatory and heart rate responses were not markedly altered or prolonged by such circulatory occlusion.3. Injection of small volumes of 5% NaCl or isotonic KCl into the arterial blood supplying hind limb muscles gave cardiovascular and respiratory responses similar to those evoked by exercise. Like the responses to exercise, these responses were abolished by dorsal root section.4. Direct current anodal block of the dorsal roots receiving afferents from the exercising muscle was used to block preferentially large myelinated fibres: this form of block did not abolish the evoked cardiovascular and respiratory responses. Local anaesthetic block of the dorsal roots was used to block preferentially unmyelinated and small myelinated fibres: this form of block abolished the cardiovascular and respiratory responses. It is concluded that the reflex responses are mediated by fibres within groups III and IV (small myelinated fibres and unmyelinated fibres).

Breathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBötzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.