Evidence of Myocardial Injury During Prolonged Strenuous Exercise*

indexes could result in left ventricular hypertrophy and myocardial dysfunction. Supporting evidence is provided by Mayet et al,5 who observed greater left ventricular mass index as well as decreased left ventricular diastolic function in black hypertensive subjects than in whites. Although plasma ET-1 levels were similarin black men and women as a group, it could be argued that estrogens in premenopausal women offset any detrimental effect of ET-1. Elderly black women who do not receive es~ogen replacementtherapy may lose this protective effect. Although our study did not include this patient subset, it has been observed that elderly hypertensiveblack women have a significantlyhigher rate of left ventricular hypertrophy than hypertensive white women at every level of blood pressure or weight.bApparentlysome factor other than bloodpressure or weight places elderly hypertensive black women at greater risk for left ventricularhypertrophy. In our study black and white women had similar ET1 levels. However, in the setting of disease, black women may be more sensitiveto the mitogeniceffects of ET-1 than white women. In contrast to the report by Polderman et al,7 we observed higher ET-1 levels in women than in men. The women in our group, although similar, were on average 7 years older, and 2390 (17 of 73) of our subjects were receiving combination birth control tablets. ET-1 is induced by agents known to modulate calciums Thus, an agent such as estrogen would be expected to increase plasma ET-1 levels. It has been reported that estrogens increase the density of endothelin receptors in the uterus in a dose-dependent manner. However, sequential administration of estrogen and progesteronehad no effect on endotheiin receptors.9Furthermore, it is not known if estrogens increase ET-1 receptors in ail tissues.Thus, the differences between these studiesremain unexplained. Interestingly, serum ET-1 levels were approximately twice as high as plasma ET-1 levels in ail

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ompetitive athletes such as long-distance runners typically manifest markedly elevated total creatine kinase (CK) enzyme serum levels, representing skeletal muscle trauma, when measured shortly after exercise. Because skeletal muscle contains a small proportion of the “cardiac” MB fraction of CK, this isoenzyme is sometimes elevated as well.’ Thus, asD

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1. Picking TG. Hypertension in blacks, Cum Opin Nephrol Hypertens 1994;3:207-212. 2. Battistini B, D’Orleans-Juste P, Sirois P. Endothelirw circulating plasma levels and presence in other biologic fluids. Lab Zmwr 1993;68:600-628. 3. Wagner OF, Christ G, Wojta J, Vierhapper H, Parzer S, Nowotny PJ, WaJ& e c t hausl W, Binder Bfi. Polar s cells. J lliol Clrerrr1992;267:16066-16068. 4. Lemran A, Hildebrand FL, Aarhus LL, Burnett JC. Endothelin has biological actions at patbophysiological concentrations. Circulation 1991;83:180,8–1814. 5. Mayet J, Shahi M, Foale RA, PordterNR, Sever PS. Racial differencesin cardiac structnmand fnrrctionirressential hypertension.BMJ 1994;308!1011–1014. 6. Sutherland SE, Ganes PC, Keil JB, Usher BW, Carabello BA, Knapp RG. Echocardiography: distribution and correlation of left ventricular mass in an elderly biracial cohort (abstr). Circulation 1993;88:700, 7. Polderman KH, Stchouwer CD, Van Kemp GJ, Dekker GA, Verheugt FW, GWren LJ. Influence of sex hormones on plasma endothelin levels. Ann Mern Med 1993;118:429-432. 8. Stephenson K, Gandhi CR, Olson MS. Biological actions of endotbeiin. Vitam Horm 1994;48:157–198. 9. Maggi M, Vannelli GB, Peri A, Brandi ML, Fantoni G, Giannini S, Torrisi C, Grrardabasso V, Bami T, Toscano V. Immunolncalization, binding, and biological activity of endothelin in rabbit uteras: effect of ovarian steroids. Am J Physiol 1991;260:E292–E305. 10.Tippler B, Herbst C, Simmet T, Evidence for the formation of endothelin by lysed red blnod cells from endogenous precursor. Eur J Pharrnacol 1994;271:131-139. 11. Mikkola T, Ristimaki A, Viinikka L, Ylikorkala O. Human serum, plasma, and platelets stimulate prostacylin and endothelin-1 synthesis inhuman vascuhm endothelid cells. L~e Sci 1993;53:283–289.

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In summary, ET-1 levels were significantly increased in black men compared with white men. This racial difference could have important research implications if increased ET-1 levels are linked to left ventricular hypertrophy and other cardiovasculardiseases,and it may serve as a foundation for future studies.

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groups.It is possiblethat during the collectionprocess red blood cells were lysed iindreleased ET-1.IOAlternatively,the high serumET-1 levelscould be the result of ET-1 induction. During the clot-forming process, thrombin, a potent itiducerof ET-1, is formed and released. Thrombin-activated platelets have been reported to signific~tly increase ET-1 synthesis in endotheliai ceils.ll A similar process may occur in polymoqhonuclear or mononuclearcells.

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surance that no cardiac injury has occurred is problematic in this setting. Recently, the detection of an elevated cardiac troponin T serum level has been found to be very specific in detecting myocardial injury2’3and has become clinically available. Isolated brief reports have been in conflict regarding the suggestion of myocardial injury in high-intensity exertion as determined by elevated serum troponin T levels.4’5 The goal of this preliminary study was to determine whether evidence of myocardial injury, as determined by elevated serum troponin T levels, woulda develop in participants in an ultramarathon race, the Western States Endurance Run. This competition inA

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volves severe prolonged physical stress, requiring participants to run 100 miles through the Sierra Mountains on steep terrain, through temperature extremes, within a period of approximately 18 m 30 hours. ... Six volunteers from among the runners were selected: all 3 entrants with known coronary disease were asked and agreed to participate. The 3 runners without known coronary disease were chosen by accepting the first 3 who presented themselves after an announcement was made at the pre-run organizational meeting of participants. Five of the 6 were available to have blood drawn at completion of their runs and composed the study population. All 5 were men, ranging in age from 53 to 62 years and in weight from 131 to 190 pounds. Three had a previous history of coronary disease and revascularization with recent negative evaluations for ischemia using stress echocardiography. Two had no known coronary disease and no known coronary risk factors in their medical records. Two ran the entire 100 miles, 1 ran 93 miles, and 2 ran 52 miles; running time ranged from 19 to 30 hours. Shortly before and after each subject’s run, blood was drawn and immediately spun, and the serum promptly placed on dry ice for transport to a deepfreeze refrigerator for storage, Cardiac troponin T levels were performed with a commercially available monoclinal antibody method (Cardiac T ELISA reagent with ES 300 Immunoassay System, Boehringer Mannheim Corporation, Indianapolis, Indiana). Results are presented in Table I. All subjects had no detectable ( <0.04 rig/ml) serum troponin T before running. At completion of the run, serum troponin T levels ranged from 0.29 to 8.55 rig/ml, all above the commonly accepted level of 0.2 rig/ml indicating myocardial injury. A history of coronary disease did not appear to be predictive of troponin T level. The markedly elevated levels were seen in both subjects who completed the entire 100 miles. As expected, all subjects had very high total CK serum enzyme levels; 2 approached, but did not reach, the relative index level of >3.0, indicative of myocardial iniurv in this hos~ital’s laboratory.

T serum level, the few existing small studies of prolonged-endurance physical activity have demonstrated either no or unusual evidence of myocardial injury during such exercise,4’sOne study did suggest that injury could occur in marathon runners, finding an elevated cardiac troponin T level in 1 of 19 participants in the Berlin Marathon,s The race in which the subjects of the current study participated was unique in that the distance run was approximately 4 times that of a standard marathon and involved stressful terrain and temperature extremes. Based on this assay, all 5 subjects in this study developed an elevated serum cardiac tmponin T level, suggesting the occurrence of myocardial injury, Given this surprising finding, it is important to consider confounding factors that could yield falsely elevated levels of this marker, That the test was calibrated or interpreted to yield falsely high levels is not likely due to no detectable troponin T being present in all 5 subjects’ prerace serum samples, which were batched with the postrace samples. Because 3 subjects dropped out of the race before the end, their postrace samples were drawn several hours later when they were located; although this may have altered the level of cardiac troponin T detected, it could not have falsely elevated it.’Although the normal stress echocardiograms of the subjects with coronary disease do not definitively eliminate their having ischemic myocardium currently, the likelihood of this is low. Finally, it has been found that with the currently commercially available assay, in the presence of a total CK serum level >5,000 U/L, nonspecific binding of troponin T to the wall of the sample tube may falsely elevate the measured levelc; among the 5 subjects studied here, however, even the 2 who had serum CK levels <5,000 U/L demonstrated elevated serum troponin T levels. It is unknown why extremely prolonged strenuous exercise should induce myocardial injury. Possibly, su,ch activity inducing a sustained elevated level of circulating catecholamines might cause focal myocardial necrosis, as observed in those with pheochromocytoma, or promote myocardial injury through adverse effects on coronary vasomotor tone.’ It cannot be excluded that = 1 of these patients, although presumed to have no flowUsing the criterion of an elevated cardiac troponin limiting coronary stenoses, may indeed have had J.

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such disease. Further study of participants in a future running of this race, using a second-generation cardiac troponin T assay that eliminates the cross-reactivity with serum CK levels >5,000 U/ L,Gis planned. These preliminary data suggest that extremely prolonged intense exercise may induce subclinical myocardial injury. Although questions of assay interference exist, the importance of this finding has prompted planning of a larger study using a methodologicallymore specific assay. Acknowledgment:We wish to thank Ezra Amsterdam, Robert Holly, Kimberly Markovich, and Hoover Ng for their counsel and assistance.

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1. Schneider CM, Dennehy CA, Rodearmel SJ, Hayward JR. Effects of physical activity on creatine phosphokinase rmdthe isoenzyme creatine kinase-MB, Arm Emerg hfed 1995;25:520–524, L H A-K. Troponin-T and CK MB (mass) in 2. G early diagnosis of ischemic myocardinl injury. Clirr Biockvrr 1993; 26:231– 240. 3. Ravkilde J, Harder M, Gerhardt W, Ljungdahl L, Pettersson T, Tryding N, Muller BH, Hamfelt ~, Graven T, Asberg A, Helin M, Penttila I, Thygesen K. Diagnostic performance rmdprognostic value of serum troponin T in suspected acute myocrrrdial infarction. Scand J Clin Lab Invest 1993;53:677–685. 4. Artner-Dworzalr E, Mair J, Seibt I, Keller A, Haid C, Prrschendorf B. Cardiac troprmirrT identifies unspecific increases of CKMB after physical exercise [letter]. Clin Chem 1990;36:1853. 5. Keller A, Mair J, Mayr M, Calzolari C, Lame C, Puschendorf B. Diagnosis of myocardial injury in marathon runners, Ann N Y Acad Sci 1995;752:234– 235. 6. Katus HA, Miiller-Bwdorff M, Hallermayer K, Zuchhold HD, Borgya A, Klein G, Ebert C, Gerhardt W. The second generation of the cardiac troponin T Elisa: improved specificity (abstr), ClirsChem 1995;41:S79. 7. Rowe WJ. Extraordinary unremitting endurrmce exercise and permanent injury to normal heart. Lmrcet 1992;340:712–714,

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n expanding array of devices are available to the “nterventional pediatric l cardiologist. These deA vices have the potential for movement when placed in a magnetic resonance imaging (MRI) unit, depending on the composition, size and geometry of the device, and magnet field strength and spatial gradients. Ferromagnetic objects also create local disruption of the magnetic field resultihg in artifact and image distortion. This study examines the safety of pediatric interventional cardiology devices by measuring deflective forces, and assesses the imaging artifacts incurred within cardiovascular MRI studies. ** Thirteen devices were studied (Table I), expanding on the array of devices previously studied by Shellock and Morisoli.l Deflection was measured in a 1.5 Tesla magnet (GE Medical Systems, Milwaukee, Wisconsin) using a previously described method.l-GEach device was suspended from a pivot point by the thread attached at its center. Using a protractor, measurements of deflection from the vertical plane were obtained at the central axis of the magnet and at the point of greatest force along the longitudinal axis of the magnet.2 When deflection approached 90°, not allowing for accurate assessment of the deflection force, a lead counterweight (nonmagnetic) was attached and the experiment was ●

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repeated. Three measurements were averaged for each device. Deflective force was calculated as: f = (m + M)g tan(@)

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Where f = force (dynes), f(g’s) = multiples of gravitational force (unitless), g = gravity = 980 cm/ S2, @ = angle of deflection from vertical, m = mass of object (g), M = mass of counterweight (g).2 To assess artifact, devices were imaged within a phantom with T1 weighting (TR 500 ms, TE 12 ms) and gradient echo imaging (TR 14 ms, TE 3.9 ms, flip angle 300). Artifact was defined as signal dropout. Distortion was defined as spatial misregistration. Artifacts were graded: O = smaller than device; 1+ = same size; 2+ = 1 to 2 times size; 3+ = 2 to 3 times size; and 4+ = >3 times size of device. Occluders were substantially deflected (forces: 6.9 to 12.7 g’s), with the exception of the secondgeneration 40 mm clamshell atrial septal defect (ASD) occluder (not deflected). Gianturco coils were substantially deflected (forces: 11.4 to 13.5 g’s). Three stents were minimally deflected (forces: 0.03 to 0.11 g’s). A platinum microcoil was not deflected. ** Artifact was greater with gradient echo imaging than T1 weighting. The spin echo in T1 weighting reduces signal loss due to local magnetic field gradients. Gradient echo imaging has no spin echo. Anatomy obscured on gradient echo imaging maybe visible on T1 weighting. Distortion was greater on T1 weighting than gradient echo, but was confined to the region of artifact. Artifact size correlated with deflective force. Of particular note is the large de●

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