PubMed1990
The intent of this paper is to review the recent literature on exercise-induced hyperammonemia (EIH) and to compare the current interpretations of ammonia accumulation during exercise with the recognized clinical symptoms of progressive ammonia toxicity. In doing so, we will speculate on possible exercise-induced symptoms of CNS dysfunction which could result from elevated ammonia during intense short-duration or prolonged exercise. Ammonia is a ubiquitous metabolic product producing multiple effects on physiological and biochemical systems. Its concentration in several body compartments is elevated during exercise, predominantly by increased activity of the purine nucleotide cycle (PNC) in skeletal muscle. Depending on the intensity and duration of exercise, muscle ammonia may be elevated to the extent that it leaks (diffuses) from muscle to blood, and thereby can be carried to other organs. The direction of movement of ammonia or the ammonium ion is dependent on concentration and pH gradients between tissues. In this manner, ammonia can also cross the blood-brain barrier (BBB), although the rate of diffusion of ammonia from blood to brain during exercise is unknown. It seems reasonable to assume that exhaustive exercise may induce a state of acute ammonia toxicity which, although transient and reversible relative to disease states, may be severe enough in critical regions of the CNS to affect continuing coordinated activity. Regional differences in brain ammonia content, detoxification capacity, and specific sensitivity may account for the variability of precipitating factors and latency of response in CNS-mediated dysfunction arising from an exercise stimulus, e. g., motor incoordination, ataxia, stupor. There have been numerous suggestions that elevated ammonia is associated with, or perhaps is responsible for, exercise fatigue, although evidence for this relies extensively on temporal relationships. Fatigue may become manifest both as a peripheral organ or central nervous system phenomenon, or combination of both. Thus, we must examine the sequential or concomitant changes in ammonia concentration occurring in the periphery, the central nervous system (CNS), and the cerebrospinal fluid (CSF) induced by any effector, not only exercise, to interpret and rationalize the diverse physical, physiological, biochemical, and clinical symptoms produced by hyperammonemic states. Since more is known about elevated brain ammonia during other diverse conditions such as disease states, chemically induced convulsion, and hyperbaric hyperoxia, some of these relevant data are discussed.