clinical investiaations Alterations in Serum Creatine Lactate Dehyd rogenase* Association Myocardial Kinase and with Abdominal Aortic Surgery, Infarction and Bowel Necrosis Go! Geoffrey M. Graeber, MG, USA, F.G.G.P;t G. Patrick Robert E. Wolf M. D. ; Patrick j Gafferty, B. S.; GolJohn W Harmon, MG, USAR;t and Norman %f. Rich, Experimental creatine studies kinase infarction. changes bowel similar documents have and shown lactate that peripheral dehydrogenase serum, change with Some clinical reports have suggested occur in patients. This prospective the changes in these enzymes that study with associated acute myocardial infarction, acute bowel necrosis (MES INF), and uncomplicated abdominal aortic reconstruction. Analysis of 15 patients with AM!, 13 patients undergoing major AAS, and eight patients with MES INF has shown that these conditions may be differentiated by analysis of serum CK and LD isoenzymes. The study suggests that in P revious and serum tion. experimental wo)rk some clinical CK becomes The reports44 elevated CK-MM elevation, but particularly is the CK-MB our from dominant rises isoenzyme early and within stays elevated, For shown that LD3 becoming experimental editorial total comment serum the bowel LD see rises dominant infarction page only = abdominal ters suggest has 519 be Research, Center, formed tProfessor the Division The of Surgery, Surgery Washington, DC Services University Service, Walter Walter Reed Army and the Department ofthe Health Sciences, Surger) Bethesda, UniMd. of Surgery and Chairman of Surger The opinions and assertions contained herein are the private views ofthe authors and are not to be construed as official or as reflecting the views of the Department of the Army, Uniformed Services Reprint University, Department accepted ofSurgery, seen which o)ther study was serum infarction seen in patients cenwith in these bowel those could in AM! and have undergone who from AAS Differentiation of these three may be required in a critical care setting the exact diagnosis is unknown and rapid uncomplicated . conditions wherein ofthe precise diagnosis of the patient. of Defense. August 25. %Vest Virginia groups patients who were cardiographic These may be essential eight their hospital isoenzyme grafts for patients either zvme analyses. to undergo occlusive or Postoperativel); serum in the were the drawn and LD. infarctions. Iii the disease samples subsequently 24 for hours five second room were and I 3 I MARCH, of days group, l)ypass were ,u,d collected I 97 analyses first daily ECGs recovery electro- aortobifemoral aneiirvsinal preoperative Samples then of 15 with isoenzyme for elective normal determinations days. CK were had fir admission of both analyses consisted tinit myocardial drawn were first care transmural with Samples The coronary samples starting who These isoenzyme serum course. 13 individuals studied. to the of acute had hours ETIIODS were admitted evidence patients ever three oi patients CHEST Downloaded From: http://publications.chestnet.org/ on 06/09/2014 AAS in patients changes in acute occur acute prospective the from AMI necrosis; and occur following whether bowel mstitutio)n changes The systems acute our similar differentiated for I Professor ofthe Health Sciences, or the received February 27; revision requests; Dr. Graeber, Department Morgantotvn 26506 from that M of Medical §Intern. University Manuscript Reports some Institute Army of reconstruction dehydrogenase; INF with in Reed aortic to test Three *From lactate MES necrosis.48 changes LD infarction; determination for the survival slightly isoenzyme MDII kinase; conducted enzyme in experimental LD in acute serum creatine = myocardial bowel animals with lethal injuSerum CK-BB also rises early, but decreases 24 hours of the infarction.”3 Monitoring of ries.’ CK 3 of the M.D.;t the absence of electrocardiographic changes, a patient with epigastric distress with elevated levels of serum CK and either CK-MB or CK-BB bands present may well have a mesenteric rather than a myocardial infarction. Acute myocardial infarction can be ruled out further through analysis of serum LD/LD2 ratios. (Chest 1990; 97:521-27) laboratory suggest that peripheral with acute bowel infarc- Glagett, studied. serum isoen- collected twice daily 1990 for daily for for an 521 Table 1-Summary Anatomic Patient No. Age/Sex 1 Area Necrotic Left 67/M colon with Patients ofCinical Necrotic Bowel of Bowel Etiology (perforation) Surgery: aortic Confirmation reconstruction Surgery and Outcome (Resection) Survived 2 60/M Left 3 65/M Right colon-mucosal slough Surgery: reconstruction aortic Embolization colon during Autopsy angiography Surgery (Resection) Autopsy 4 80/F jejtinum, ileum and right half Embolus; iletim and right half Thrombosis mitral stenosis Autopsy of colon 5 741M Jejunum, of colon 6 67/NI Jejunum and ilet,m Autopsy of superior mesenteric Emboli artery after cardiac Surgery catherterization 7 1) Distal 56/M 2) Small 8 601M additional five patients serial were ECGs consisted of Confirmation and returned diographic for sample ten the performed eight individuals with to normal. infarction minutes using patients These had occurred. at 3,000 standard twice pipettes. and all ofcolon third also Senim Serum samples was total speetrophotometry.23 using gel measurement or preop- both CK and were whether LD reported an analysis been reviewed Use Committees each consent were right forms to withdraw compiled evaluated they are values by Wilcoxon from the distribution each Perceived rank-sum between normal for graphed. significant this prospective by the Clinical of Walter Reed by both from and were entered passed approved the were Results test to groups.’ All reflecting test. voluntarily and Isoenzymes electrophoresis.23 tabulated, of a one-sided All patients centrifuged from were determine values myo- agarose differences electrocar- and Autopsy by automated whether CK hernia determined drawn were Died internal determined infarction. extracted Surgery the at operation daily to and bowel had due unit of patients until flow atherosclerosis group were low days, care obtained daily Autopsy and Strangulated to determine All blood rpm. Thrombosis postoperative determinations postoperatively colon of ileum suspected was at least and intensive The infarction Enzyme bowel two surgical daily. postoperatively monitoring first in the were in all cases. eratively cardial During mo)nitored of mesenteric at autopsy LD days. feet Six ileum the study Army and time which and Center. Medical committees at any study Investigation had without had Human All signed the voluntary incurring any (Graeber et a!) SERUM TOTAL Ck lUlL ----1 #{149}ALS*MPLE1 SAMPLE2 -------1-- - DM2 DM3 DM4 DAY5 total CK values for all three groups of patients in this study. Bars represent standard mean. The horizontal line at 100 lU/L represents the upper limit of normal for our laboratory. Note that all three groups started out with initial CK values which were comparable. Patients having either necrotic bowel or AMI had elevation of serum total CK within eight hours of admission. Their maximum values were reached between 16 and 24 hours after their clinical events. They then had a subsequent gradual decline in this measurement. FIGURE errors 1. - Serum of the 522 Downloaded From: http://publications.chestnet.org/ on 06/09/2014 CK and LDH after Mesentenc Infarction Table 2-Change8 CK and its lsoenzymes in Serum (All CK Total Maximal (IUIL± SEM) Values) CK-MB CPK-BB (% ± SEM) (% ± SEM) CK-MB SEM) (IU/L± Are Mean Values AcuteMl(N-15) 689±159 166±59 19.5±2.3* Bowel necrosis 786±284 192±20 12.8± Major aortic reconstruction limits ofnormal Upper *p<0.01 = 13) ± 51 367 12 ± 7 100 by Student’s in status changes (N unpaired t-test or alteration when compared in optimum medical values recorded care. groups consisted the coronary care an acute transmural by serial with bowel undergoing samples bowel patients unit who were myocardial diagnosed infarction admitted to as having confirmed ECGs. There were 13 patients identified necrosis. The patients with AM! and those major aortic reconstructions all had serum determinations course with of LD their bowel infarctions. vanced so far into their Two clinical as a result of the bowel bowel necrosis had isoand CK subsequent other patients courses ofsevere with bowel decrease enzyme 3. 1 ± 1.3 0 <5 0 to had adbowel infarction that their enzymes were deemed unreliable for isoenzyme analysis. These two patients had profound hypoperfusion syndromes which promoted gen35 SERUM necrosis. in perfusion release from of the entire many organs. had elevations in serum who had AM! had the most CK. rapid rise their repair in serum a bowel body with Only one patient subsequently survived ble 1). All three groups ofpatients total CK (Fig 1). The patients however, started had comparable drawn as noted. Those patients who had necrosis had fewer samples drawn because were taken to the operating room or died early in their hospital infarction. Six patients enzyme of 15 patients for patients eralized resulting RESULTS Patient 4.3±0.8 <50 with 0 1.5 total Each out at comparable values within the clinical events. of abdominal The aortic infarction ofthe (Ta- groups, initial levels first 24 hours patients aneurysms who did and after underwent not show elevations above the upper limits of normal until the second sample taken on the evening of their operative day. These patients had elevated levels of serum total CK throughout patients who hospitalization the rest of the study course. had necrotic bowel had initial values which were within normal limits, The on but their subsequent values rose within 8 hours after admission and reached a maximum on the first hospital day. The values for these patients have been plotted CK-MB-- (%) 30 25 % 20 15 5 - UmAL SAMPLE1 SAMFLE2 DM2 - ---.-.--.-‘ DAY3 DM4 DAY 5 Ficutox studied. 2. Serum CK-MB expressed as a percentage of the serum total CK for each of the three groups Bars represent standard error of the mean. All three groups started with mean values below 5 percent. The AAS group had minimal elevations which were not significantly different from preoperative determination. The AM! and MED INF groups rose to higher levels than the AAS group in the first day (p<0.01). The AM! group was significanfly higher than the other two groups only during the first day. The AM! and MES INF grOupS were not statistically different from one another by the day 2 samples. CHEST Downloaded From: http://publications.chestnet.org/ on 06/09/2014 I 97 I 3 I MARCH, 1990 523 SERUM C k-MB OUIL) 350 300 lUlL #{149}m*t s*ui mean. bowel groups through into a terminal or went the DM2 second day hypoperfusion to surgery since they proceeded syndrome for correction. reconstructions and! there were units than Pa- lions in the reconstruction; Hence, tients who were admitted with AM! had elevations on their 8 hour samples (sample 1), and reached maximum levels on the samples taken between 18 and 22 hours after their myocardial infarctions. Day 2 actually represented their first full hospital day and should be viewed as a period of time from 24 to 48 hours after the clinical event. The differences were not statistically significant between in the first as determined rank-sum by the Wilcoxon the groups three days test. groups. The patients who had elevated levels within 12 hours after surgery within the upper range of normal (less than AAS had that were 5 percent) and these elevations did not exceed the upper limit of normal at any time throughout the study. In the first three days of the study, there was no difference in the CK-MB percent between the patients having AM! and those having MES INF. Both groups, however, were different from those patients who had major 524 Downloaded From: http://publications.chestnet.org/ on 06/09/2014 of the Determination DAYS MES per liter !NF abdominal ofthe showed serum that aorta CK-MB there were group of patients that however, the groups showed marked elevations (pcZO.OO1). in international minimal eleva- had major aortic that had AM! or within the first three days after their clinical events (Fig 3). Maximum values for CK-MB (IU!L) were reached approximately 16 to 24 hours after the clinical events in both those groups. There were fairly marked variations in the amount patients of CK-MB present within these groups. The with necrotic boweland those with myocardial infarctions other Electrophoretic isoenzyme determinations allowed the serum CK-MB levels to be expressed as a percentage of the total CK. Two groups had elevations above the upper limits of normal (5 percent), the patients who experienced AM! and those having necrotic bowel (Fig 2). Maximum values from CK-MB percent were reached by 16 hours after the clinical in both DAY4 (sepsis) few samples to measure from these patients more 48 hours after the onset of the bowel infarction. event DM3 3. Values of CK-MB (lUlL) for all three groups of patients. Bars represent standard errors of the Note that significant elevations are apparent in those patients having AM! and in those who had necrosis. Elevations overlap in these two groups between day 2 and day 3; however, both of these had significantly greater values (p<0.01) than those patients who had major aortic reconstruction. FIGURE only SAMPLE2 could based on not be differentiated these measurements one alone from on anday and day 3 following the onset of their clinical events. Analysis of the CK isoenzyme tracings for all three groups of patients for CK-MB six patients who had CK-BB bands in their of the study. None of bands in their sera at showed that only the necrotic bowel had detectable serum within the first 24 hours the other patients had CK-BB any time (Fable 2). The serum CK-BB bands infarction. samples For those patients available for evaluation, diminished by the second day after who had late serum there were no CK- BB bands present in any of the serum samples on the third day after bowel infarction. Analysis of serum total LD showed that all three groups had elevations above the upper limits of normal within 16 hours after each clinical event (Fig 4 and Table 3). All three groups of patients were somewhat CK and WH after Mesenteric Infarction (Graeberet&) 2 SERUM TOTAL LO 525 450 375 300 lUlL 75 .mAL UM SAMPLE2 1 DAY2 FIGURE 4. Serum total LD is presented. Bars represent at 110 lUlL represents the upper limit of normal for with nearly identical value for total LD. Patients having greater values for LD by 24 hours following their event These two groups could not be differentiated from one overlapping within patients with significantly LD values the first MES different on the INF 24 hours and (p’(O.Ol) 2 and day compared with those recorded AAS. They were not, however, one from the Serum patients MES of the study. with AM! were in their serum day 3 samples total when those in patients having significantly The INF and those tion had LD1ILD2 all samples while who ratios patients had which who major aortic had evidence of an LD3 dominance patterns at any time following their (Table DIsCussIoN Previous mesenteric experimental infarction causes studies an CK within the first 24 hours after an infarction. three isoenzymes of CK also become elevated within that same time period.2’3 The majority of the ‘ reconstruc1.00 on infarc- enzyme elevation BB being present is CK-MM, with CK-MB and CKbut being substantially less than the of CK-MM the CK showed tracings in the patients that these patients had between the major aortic total significant one taken those having necrosis was (p<O.Ol) for all samples subsequent on the evening of the day of their event. Analysis of the isoenzyme tracings patients who had acute bowel infarctions Table 3-Changes in Serum its Isoenzymes Bowel necrosis Major aortic *p<0.01 (Values = 8) by Student’s (N unpaired = 13) t-test when compared LD/LD, Maximum evaluation that had elevations as did the patients who and AM!. All three of Dominant ±(SEM) Percent !soenzyme of Patients Showing 1.21±0.05* LD, (15/15”lOO%) 0.74 ± 0.8 LD3 (4/6 201 ± 21 0.68 ±0.92 LD2 (13/13 with values of MES INF of serum Determinations) for patients with bowel necrosis or after major CHEST Downloaded From: http://publications.chestnet.org/ on 06/09/2014 Clinical ± 69 424 reconstruction Mean Ratio SEM) 323±47 (N in the first 24 hours aortic reconstructions Are LD Total (IU/L± present.2’3 groups went above the upper limit of normal (100 lUlL) for our laboratory within this time frame. Differentiation between these three groups of patients based on this measurement was not possible. from the six showed that AcuteM!(N=15) CK had major to the hospital LD and shown that of serum total amount AM! and or bowel have elevation The tions had values greater than 1.00 by 16 hours after onset of the infarction, and values remained elevated throughout the remainder ofthe study. The difference patients having reconstructions in their clinical 3). major groups of who had were less than had myocardial DAYS standard errors of the mean. The horizontal line our laboratory. Note that all three groups start off AM! and those with necrotic bowel had significantly than did patients having major aortic reconstructions. another based on measurement ofthis enzyme. events different of all three the patients DAY4 only four isoenzyme other. isoenzyme analyses for LD showed that DAY3 aortic I 97 67%) 100%) reconstruction. I 3 I MARCH, 1990 525 L01 I 1.02 RATIO I .40 .20 .80 .60 .40 .20 im*i. uui 5.The FIGURE initial values. deviation LD/LD from became to rise durparticularly elevated above the limits of normal (5 percent) in the group who had AM! and those having acute bowel (Fig 2). Differentiation between the group having AM! and the one with possible based the peripheral on the CK-MB serum because in two three hours of the after the time clinical bowel periods events. necrosis percentage the values was the between not first AAS centage remained Analysis of the tional units was possible below serum per liter showed since 5 percent CK-MB the CK-MB 36 these per- in this. group. in terms of interna- that the group with bowel necrosis and the one with AM! had similar values during the second and third days after their clinical events. Patients who had necrotic bowel had values based on this determination during the first day after onset aortic which were reconstruction. closer to those Differentiation seen after major of the patients 526 Downloaded From: http://publications.chestnet.org/ on 06/09/2014 with necrotic struction bowel was from those possible (Fig 3). One of the most on who the had aortic second important and recon- third measurements day for dif- ferentiating bowel necrosis from myocardial infarction appears to be serum CK-BB elevations seen after bowel infarction. This isoenzyme was not found in any of the patients who had major aortic reconstructions nor in any of those patients who had AM!. This band may be present in patients who have chronic renal present in were similar within Overlap upper of patients infarctions of patients two groups became more apparent in the subsequent course. Differentiation of the groups of patients with either bowel or myocardial infarctions from the group undergoing DAYS for each of the groups of patients studied. All three groups had overlapping with necrotic bowel and those having major aortic reconstruction had no their initial levels at any time throughout the study period. Those patients with AM! had that exceeded the 1.00 level by 16 hours following their clinical events and these elevations throughout the remainder ofthe study period. in those experimental subjects who have lethal infarctions, analysis of serum CK-MB was conducted both in terms of percentage of the total and in terms of international units per liter found in the serum.2’3 CK-MB DAY4 patients Because serum CK-MB has been shown ing the latter portion ofbowel infarctions, Serum DAY3 ratios Those LD/LD2 ratios were maintained DAY2 SAMPLE2 failure, metastatic cancers, cular accidents, nervous system can be and have trauma.5’6 differentiated clinical basis. Serum total patients LD from was three and groups capable These results ofdifferentiating findings agree which suggest elevated had by acute bowel elevated there was much (Fig 4). This with that bowel recent cerebral vas- experienced major central These conditions obviously infarction in all three on a groups of overlapping between enzyme system was the not the groups from one another. our previous experimental LD may be only minimally infarction but other conditions (such as myocardial infarctions or major aortic reconstruction) can cause elevations above the upper limits ofnormal for this enzyme.3 The ratio of LD1ILD4 was quite capable of differentiating patients with AM! from patients with acute bowel infarctions and patients CK and WH undergoing after Mesenteric Infarction major (Graeber AAS et a!) (Fig 5). greater The only than patients 1.00 graphically were proven other two the serum groups samples who those AM!. had who None LD1/LD2 had of the had this isoenzyme evaluated Other . in ratios patients electrocardiopatients in the the change in any of clinical conditions which renal can cause infarction this change and hemolysis LD1/LD2 of blood These bowel conditions infarction can be differentiated or myocardial infarction ratio are ‘#{176} from acute on a clinical basis. The prospective isoenzymes has ential bowel tion.” results Clearly, elevation of the serum level is not specific for myocardial Necrotic of this investigators for CK-MB necrotic levels study, were must also also explain CK-MB infarc- be considered. why other ischemic ofthese transient bowel. enzymes character The elevations in can be missed. of the elevations means total does as well as the changes which aortic surgery. With acute CK and LD will be elevated LD will 1 Graeber JW. by the presence of serum CK-MB bands a LD ratio LD1/LD2 greater than 1.00. In be elevated but isoenzyme will be detected patients. GM, GM, JW. and its superior 3 Graeher in the MJ, Changes in serum post- et GR. lactic Appearance of a patient Chem Acta 1979; 92:4115-119 5 Lamar L, kinase-BB isoenzyme. M The . GM. 7 Graeber through In: Harmon mucosal cell injury Wilkins, 1981:77-93 MI, elevations a patient New 10 Galen Pathol Verrill in serum with WJ, York: Massey GM. isoenzyme in the colon. Clin implications in serum: of 299:234-35 a summary bowel of muc()sal in the of gastrointestinal Baltimore: WF Jr. injury (CPK) Mechanisms Williams Marked and peripheral and concomitant kina,se and lactic dehydrogenase Am Surg 1983; 49:612-15 FJ. Introduction enzyme in acute 194:708-15 1978; isoenzymes necrosis. RE, (LDH) phosphokinase Mueller creatine McGraw-Hill, 1975; perioperative ML, Wolf creatine of the Med ischemic ed. JF, 65:351-55 and cytoprotection. bowel RS. The 11 Graeber JW, of serum 1981, Clinical (BB) creatine (LDH) ligation 193:499-505 BB J 1976; ofearly of dehydrogenase Okoye Pathol Detection serum. BE. N Engl of CPK1 Clin measurement lactic 9 Dixon J Am Surg infarction Statland detection cases. 1981; kinase from W, Voodward creating 6 Itano suffering Ackerman experimental dehydrogenase Ann Harmon phosphokinase peripheral ofcreatine serum CP, Curley PJ, O’Neill in infarction. CP, in experimental creatine Surg Cafferty Changes and colonic by Ann DK, al. Curley 31:148-50 total caused artery. (CPK) experimental 8 1980; Wukich NB, phosphokinase 4 Doran Forum Reardon isoenzymes GM, MJ, phosphokinase PJ, mesenteric Ackerman Reardon Surg Cafferty Harmon (CPK) the PJ, creatine infarction. Graeber NB, Cafferty ofserum to statistical in analysis. 1969, infarction. Hum 1969:344 diagnosis of myocardial 6:141-55 Creatine myocardial kinase (CK): infarction. its use Surg in the Clin evaluation N Am 1985; of 65: 539-51 CHEST Downloaded From: http://publications.chestnet.org/ on 06/09/2014 reconnecro)sis, The authors wish to express their gratiand Ms. Vickie L. Close for preparation G. Ellis Elevations mesenteric 2 attend bowel but the may be obtained by analysis of LD isoenzymes which will show an LDJILD2 ratio less than 1 .00 following the infarction. Acute myocardial infarction can be aortic of ischemic REFERENCES sixteen presence of both serum CK-BB and CK-MB will suggest the diagnosis of bowel necrosis rather than myocardial necrosis. Confirmation of necrotic bowel major evidence for LD will be normal with an LD1/LD2 is less 1.00. Only CK-MM, and perhaps, ACKNOWLEDGMENT: tude to Mrs. Linda of the manuscript. that the findings suggest that evaluation of systems can differentiate between AM! and bowel necrosis major abdominal infarction, serum diagnosed along with uncomplicated any small traces of CK-MB operative serum of these the In addition, failure to find these isoenzyme levels elevated not exclude the diagnosis of necrotic bowel. In summary, two isoenzyme serum distributions ratio which The clinical ofthese isoenzymes were clearly evident in this but they were transient. If the blood samples not taken during the relevant time period, the elevation the bowel study necrotic surgery have conflicting results when they looked and CK-BB in the serum of patients with or have without evaluation ofCK and LD and their important implications for the differ- diagnosis of myocardial infarction and particularly in postoperative aortic patients. isoenzyme who struction I 97 I 3 I MARCH, 1990 527