PHYSIOLOGICAL INTRAVASCULAR HEMOLYSIS OF EXERCISE. HEMOGLOBINEMIA AND HEMOGLOBINURIA FOLLOWING CROSS-COUNTRY RUNS D. Rourke Gilligan, … , M. D. Altschule, E. M. Katersky J Clin Invest. 1943;22(6):859-869. https://doi.org/10.1172/JCI101460. Research Article Find the latest version: https://jci.me/101460/pdf PHYSIOLOGICAL INTRAVASCULAR HEMOLYSIS OF EXERCISE. HEMOGLOBINEMIA AND HEMOGLOBINURIA FOLLOWING CROSS-COUNTRY RUNS By D. ROURKE GILLIGAN, M. D. ALTSCHULE, AND E. M. KATERSKY (From the Medical Service and the Medical Research Laboratories, Beth Israel Hospital, and the Department of Medicine, Harvard Medical School, Boston) (Received for publication May 19, 1943) Studies on 3 cases of march hemoglobinuria were introduced into a tube containing 0.5 cc. of 3.0 per were recently reported from this laboratory and cent sodium citrate solution. The tube was stoppered and gently inverted several times to secure mixing. The the existing literature concerning this syndrome plasma specimen was removed from the citrated blood was reviewed (1). In 1 patient of our series and samples from one-half to one and one-half hours after in some other reported instances, frank hemo- the blood was drawn. In many instances, 5.0 cc. of ad- globinuria has been observed following walks of ditional blood were placed over oxalate mixture for only 20 minutes' duration. Such occurrences are studies of hematocrit and of erythrocyte fragility. A sample of urine was collected shortly after blood was obviously unusual and are considered to be due to taken. Examination of the abdomen for the presence of some as yet unrecognized and apparently benign hepatic or splenic enlargement was made at the end of abnormality (1). There are, however, other re- exercise. ported cases in which hemoglobinuria occurred Chemical methods. The chemical methods utilized were only after very long, strenuous walks or after long described in detail in a previous publication (3). The runs. concentration of hemoglobin in the plasma and urine was The question arises whether intravascular measured by the benzidine method as described by Bing hemolysis, giving rise to hemoglobinemia and and Baker (4, 5), with slight modification (3). Tests sometimes hemoglobinuria, occurs with sufficient showed that no appreciable change in the plasma hemo- frequency in certain types of strenuous exercise of globin value occurred when the citrated blood sample re- long duration to be considered physiological. To mained at room temperature for 2 hours before separat- in a ing the plasma; these tests were made in order to make gain information this regard, study was made certain that the necessary standing of the blood for from of the incidence and degree of intravascular he- 30 to 90 minutes, between the time it was drawn at the molysis in normal individuals performing long place of termination of the exercise and the removal of strenuous runs; the results of these studies and the plasma in the laboratory, resulted in no measurable of other urinary and blood studies pertinent to the hemolysis. It was also demonstrated that the amount of problem are reported and hemoglobin in the plasma was not affected by transport- discussed herein. ing the blood from the field to the laboratory. The plasma hemoglobin values of some 50 normal subjects, who had MATERIAL AND METHODS not undertaken any strenuous exercise on the day of Material. Studies were made in groups of young sub- study, revealed values usually of 1.0 to 6.0 mgm. per 100 jects performing runs as follows: (1) 11 men, aged 17 to cc., with a rare value between 6.0 and 9.0 mgm. per 100 18 years, after a cross-country run of 2.6 to 2.8 miles, in cc. and an average value of 4.0 mgm. per cent. We be- 14 to 18 minutes; (2) 11 men, aged 19 to 21 years, after lieve that this variability between 1.0 and 6.0 mgm. of a cross-country run of 4.5 to 5.1 miles, in 23 to 31 min- hemoglobin per 100 cc. of plasma is not a true variability utes; and (3) 26 men, aged 18 to 65 years, after a mara- in the plasma concentration of the circulating blood, but is thon run of 10 to 262 miles. In addition, comparative more likely occasioned by slight in titro changes. This studies were made in 1 subject after the 26.2 mile mara- impression is gained from the fact that 2 blood samples, thon run, after a 5-hour period of exercise on the bicycle drawn within a period of a few minutes from a given ergometer, after a 262 mile walk with a 52-pound pack subject at rest, not infrequently vary by 2.0 to 4.0 mgm. on his back, and after an additional run of 112 miles in per 100 cc. Although it is perhaps true that minimal 76 minutes and 19 seconds. extravascular hemolysis cannot be avoided, no plasma Methods of study. A blood sample was taken from an hemoglobin value after exercise has been considered in- antecubital vein, without stasis, within 15 minutes after creased unless it was higher than the uppermost limit completion of exercise. The blood for plasma hemo- encountered in normal resting individuals, namely, 9.0 globin measurement was drawn as suggested by Ham mgm. per 100 cc. 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Cd 93 -W :3 -a .m W r Ca - 0 o 0% .cn C) -w8.9W .0 C: 0000qC 0 50F.00o00o.0 eqC)C)~ U) +%Oab000%0'- ac ) cn O uuuuu ououesoo CO 4-. 4)4* *i*) -U*.*.- t. .) U) in Uin In - - t- - in eq4 eqeqC4v4C4V- 4~~4.h _~~+4 Cd C.)C.) OC.OC)C.C.C. a) 0000 ZOZOOQO a)i4J4- J J4 4 - 00000 0o0oooo U 0 U U U 0i UU Z Z oz INTRAVASCULAR HEMOLYSIS OF EXERCISE 861 tal protein concentration of the urine was measured gravi- passed a red urine after a race in 1939, i.e., a year metrically after precipitation with trichloroacetic acid before these statistical studies were made, and (3). When the total protein was less than approximately studies. In both 30 mgm. per 100 cc., the concentration was estimated by again in 1941, a year after these comparison of the turbidity of the urine with that of instances, the urine became normal in color and standards after the addition of 5.0 per cent solution of showed no hemoglobin or albumin on the morning sulfosalicylic acid. Spectrophotometric examination of following the race. There were no symptoms at plasma and urine specimens were made for us by Dr. the time of the hemoglobinuria. 0. H. Lowry of the Department of Biochemistry of the The plasma hemoglobin values Harvard Medical School; a Ko5nig-Martens type of Marathon runs.