Alfaro, V., J. Pesquero, and L. Palacios. Acid-base disturbance during hemorrhage in rats: significant role of strong inorganic ions. J. Appl. Physiol. 86(5): 1617-1625, 1999.-The present study tests the hypothesis that changes in the strong inorganic ion concentrations contribute significantly to the acid-base disturbance that develops during hemorrhage in the arterial plasma of rats in addition to lactate concentration ([Lac Ϫ ]) increase. The physicochemical origins for this acid-base disorder were studied during acute, graded hemorrhage (10, 20, and 30% loss of blood volume) in three groups of rats: conscious, anesthetized with ketamine, and anesthetized with urethan. The results support the hypothesis examined: strong-ion difference (SID) decreased in the arterial plasma of all groups studied because of an early imbalance in the main strong inorganic ions during initial hemorrhagic phase. Moreover, changes in plasma [Lac Ϫ ] contributed to SID decrease in a later hemorrhagic phase (after 10% hemorrhage in urethan-anesthetized, after 20% hemorrhage in ketamine-anesthetized, and after 30% hemorrhage in conscious group). Inorganic ion changes were due to both dilution of the vascular compartment and ion exchange with extravascular space and red blood cells, as compensation for blood volume depletion and hypocapnia. Nevertheless, anesthetized rats were less able than conscious rats to preserve normal arterial pH during hemorrhage, mainly because of an impaired peripheral tissue condition and incomplete ventilatory compensation. strong-ion difference; ion imbalance; metabolic acidosis; anesthesia; ketamine; urethan METABOLIC ACIDOSIS IN BLOOD is common during hemorrhage (8, 17). Reduction in blood volume during hemorrhagic shock results in decreased cardiac output and decreased O 2 delivery to tissues (8,10,17,29). This latter may increase the activity of the anaerobic energyproducing systems or decrease aerobic energy-producing systems during hemorrhagic shock, thus raising lactic acid concentration of extracellular fluid and reducing plasma HCO 3 Ϫ concentration ([HCO 3 Ϫ ]) (17). However, hemorrhage also results in changes in the main plasma inorganic ions and proteins (6,10,16,18,(37)(38)(39)41).In 1983, Stewart (35) designed an approach for the study of acid-base changes in body fluids, which assumes that ion and protein changes influence the acid-base balance in a physiological compartment, arterial plasma in the present study. Several authors have used this physicochemical approach to quantify mixed acid-base disorders (3-5, 21, 25, 27, 40). The physicochemical analysis is done by combining the state of electroneutrality with the state of equilibrium for all incompletely dissociated substances and the solvent, water. Three sets of variables that are relevant to the acid-base balance can be changed primarily and/or individually in vivo. They can be regarded as independent variables and are the PCO 2 , the strong-ion difference (SID), and the total concentration of weak acids ([A tot ]). PCO 2 represents t...