Acid-base balance at exercise in normoxia and in chronic hypoxia. Revisiting the "lactate paradox".

Transitions between rest and work, in either direction, and heavy exercise loads are characterized by changes of muscle pH depending on the buffer power and capacity of the tissues and on the metabolic processes involved. Among the latter, in chronological sequence: (1). aerobic glycolysis generates sizeable amounts of lactate and H(+) by way of the recently described, extremely fast (20-100 ms) "glycogen shunt" and of the excess of glycolytic pyruvate supply; (2). hydrolysis of phosphocreatine, tightly coupled with that of ATP in the Lohmann reaction, is known to consume protons, a process undergoing reversal during recovery; (3). anaerobic glycolysis sustaining ATP production in supramaximal exercise as well as in conditions of hypoxia and ischemia, is responsible for the accumulation of large amounts of lactic acid (up to 1 mol for the whole body). The handling of metabolic acids, i.e., acid-base regulation, occurs both in blood and in tissues, mainly in muscles which are the main producers and consumers of lactic acid. The role of both blood and muscle bicarbonate and non-bicarbonate buffers as well as that of lactate/H(+) cotransport mechanisms is analyzed in relation to acid-base homeostasis in the course of exercise. A section of the review deals with the analysis of the acid-base state of humans exposed to chronic hypoxia. Particular emphasis is put on anaerobic glycolysis. In this context, the so-called lactate paradox is revisited and interpreted on the basis of the most recent findings on exercise at altitude.