Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise WILLIAM STRINGER, KARLMAN WASSERMAN, RICHARD CASABURI, JANOS P6RSZASZ, KAZUHIRA MAEHARA, AND WILLIAM FRENCH Division of Respiratory and Critical Care Physiology and Medicine, Harbor-University of California at Los Angeles Medical Center, Torrance, California 90509 Stringer, William, Karlman Wasserman, Richard Ca- saburi, JAnos Pbrszkz, Kazuhira Maehara, and William French. Lactic acidosis as a facilitator of oxyhemoglobin disso- ciation during exercise. J. Appl. PhysioZ. 76(4): 1462-1467, 1994.-The slow rise in 0, uptake (vo2), which has been shown to be linearly correlated with the increase in lactate concentra- tion during heavy constant work rate exercise, led us to investi- gate the role of H+ from lactic acid in facilitating oxyhemoglo- bin (0,Hb) dissociation. We measured femoral venous PO,, 0,Hb saturation, pH, Pco,, lactate, and standard HCO, during increasing work rate and two constant work rate cycle ergome- ter exercise tests [below and above the lactic acidosis threshold (LAT)] in two groups of five healthy subjects. Mean end-exer- cise femoral vein blood and VO, values for the below- and above-LAT square waves and the increasing work rate protocol were, respectively, PO, of 19.8 t 2.1 (SD), 18.8 t 4.7, and 19.8 t 3.3 Torr; 0, saturation of 22.5 k 4.1,13.8 k 4.2, and 18.5 * 6.3%; pH of 7.26 * 0.01, 7.02 t 0.11, and 7.09 t 0.07; lactate of 1.9 t 0.9, 11.0 t 3.8, and 8.3 * 2.9 mmol/l; and VO, of 1.77 * 0.24, 3.36 t 0.4, and 3.91 t 0.68 11 min. End-exercise femoral vein PO, did not differ statistically for the three protocols, whereas 0,Hb saturation continued to decrease for work rates above LAT. We conclude that decreasing capillary PO, accounted for most of the 0,Hb dissociation during below-LAT exercise and that acidification of muscle capillary blood due to lactic acido- sis accounted for virtually all of the 0,Hb dissociation above LAT. femoral vein; oxygen pressure; pH; partial pressure of carbon dioxide; lactate; standard bicarbonate; constant work rate ex- ercise; increasing work rate exercise AFTER THE FNSET of constant work rate (CWR) exercise, 0, uptake (VO,) reaches a constant value by 3 min if the work rate does not induce a lactic acidosis (9, 10, 14, 16, 19, 30). However, if the exercise is performed at a level that induces a lactic acidosis, VO, continues to increase past 3 min of exercise (6,19,22,30) and the rate of rise in Vo2 after 3 min correlates linearly with the increase in lactate (6,8,1&Q 32). This finding led us to hypothesize that lactic acid production might be important in facili- tating oxyhemoglobin (0,Hb) dissociation (Bohr effect) when capillary PO, reached a minimum value. The initiating event in this mechanism would be the fall in capillary PO, to a critically low value when 0, demand exceeded 0, supply in the muscle during heavy exercise. Wittenberg and Wittenberg (31) postulated that the “critical” capillary PO, is between 15 and 20 Torr. Below this value, adequate transport of 0, cannot occur because of physical factors that limit diffusion be- tween the red blood cell and the sarcoplasm of metaboli- cally active muscle. Therefore, net lactate accumulation should occur in the exercising muscle (4,13,23,24). The newly formed lactic acid (acidic dissociation constant = 3.8) must be virtually completely buffered in the cell on formation because it is >99.9% dissociated at cellular pH. Because HCO, is the predominant buffer of lactic acid (1,28), CO, is released from the cell in excess of that formed from aerobic metabolism. Simultaneously, there is exchange of HCO, for lactate between the cell and the extracellular fluid, resulting in a decrease in blood HCO,. Both the increase in CO, production over that from aero- bic metabolism and the decrease in extracellular HCO, acidify the blood, causing a downward and rightward shift in the 0,Hb dissociation curve and allowing contin- ued 0,Hb dissociation during heavy exercise. The objectives of this study were to determine 1) whether end-capillary PO, as approximated by femoral venous PO, reaches a minimum (critical) value before femoral vein lactate begins to increase and 2) whether the primary mechanism for 0,Hb dissociation changes from one of decreasing PO, during moderate exercise to one of decreasing pH during heavy work rate exercise. METHODS Subjects After institutionally approved informed consent was ob- tained, five healthy nonsmoking male subjects participated in an increasing work rate protocol and five different healthy non- smoking male subjects participated in two CWR exercise pro- tocols. Before the study day, each participant performed a preliminary increasing work rate exercise test on an electro- magnetically braked cycle ergometer (Godart, DeBilt, The Netherlands) to establish his exercise capacity, lactic acidosis threshold (LAT; by the V-slope method) (2), and maximal VO, wo l Vo, averaged over last 30 s of exercise). 2max9 Catheter Placement On the day of testing, the subjects reported to the exercise laboratory after consuming a light meal with no caffeinated beverages. The right groin was shaved, cleaned, and anesthe- tized with lidocaine. Under sterile conditions, a lo-cm 8-Fr sheath (Cordis, Miami, FL) was inserted percutaneously into the right femoral vein at 2 cm below the inguinal ligament using the Seldinger technique. The sheath was secured with a single suture, and the catheter tip was positioned -4 cm above the inguinal ligament. The catheter was attached to an infusion apparatus (ContinuFlo, Baxter Healthcare, Deerfield, IL) that provided a slow continuous flow (15 ml/h) of heparinized nor- mal saline (1,000 U heparin/l) and facilitated periodic bolus flushing of the catheter. During the progressive increasing work rate protocol, a bra- chial artery catheter was placed before exercise using the Sel- dinger technique and was flushed in the same way as the femo- ral vein catheter described above. Exercise Protocols Increasing work rate test. Five subjects performed increasing (25-40 W/min) work rate exercise to maximum tolerance. 1462 0161-7567194 $3.00 Copyright 0 1994 the American Physiological Society