心肌肌钙蛋白T对冠状动脉旁路移植术患者围术期心肌梗死的诊断意义

目的：观察心肌肌钙蛋白T（cTnT）与肌酸激酶同功酶（CK-MB）在冠状动脉旁路移植（CABG）术围术期变化,比较两者对心肌损伤的诊断差异,研究cTnT对CABG术围术期心肌梗死的诊断意义。方法：连续152例患者在心脏停跳体外循环下行CABG术,平均年龄62.5±20.7（39~80）岁,平均每例移植血管2.7（1~5）支,平均心肺转流（CPB）时间113±54min,平均主动脉阻断时间56±31min。围术期9个时间点取静脉血标本,测定cTnT与CK-MB。结果：cTnT与CK-MB均于主动阻断钳开放后明显升高,开放后10h达峰值。CK-MB术后5d恢复至术前水平,而cTnT术后10d才恢复至术前水平。13例围术期心肌梗死（PMI）患者术后各时间点所测cTnT均显著高于无PMI者,术后10h达峰值,为2.97±1.12μg.L-1,且术后10d仍明显高于正常范围,为0.87±0.31μg.L-1,其中有7例术后因PMI而死亡。而无PMI者,无1例因心脏原因死亡。结论：cTnT与CK-MB在CABG术后前期的动态变化相似,但cTnT高于正常值的持续时间长,对心肌缺血损伤诊断时间窗宽于CK-MB。因此,cTnT诊断心肌损伤的晚期敏感性高于CK-MB。围术期cTnT的检测是诊断PMI高度敏感性指标,也是预测CABG术后发生PMI及预后的可靠指标。     

Detection of creatine kinase BB isoenzyme in sera of patients undergoing aortocoronary bypass surgery.

Creatine kinase BB isoenzyme (CK-BB) was detected intraoperatively in 22 of 25 patients undergoing aortocoronary bypass surgery, both in the coronary sinus and in the mixed venous blood. In a group of 10 patients in whom selective intracavitary profound hypothermic arrest was used, CK-BB values were lower than in another group of 10 patients, in whom controlled ventricular fibrillation with moderate total body hypothermia was instituted. This latter group also had higher levels of CK-MB. Patients who developed acute myocardial infarction immediately prior to or during the surgical intervention had the highest CK-BB values. This enzyme appeared as early as 15 minutes after the institution of cardiopulmonary bypass and disappeared within 6 hours. It is considered that part of the BB isoenzyme in serum of patients undergoing heart surgery is of myocardial origin.     

Cardiac troponin I: its contribution to the diagnosis of perioperative myocardial infarction and various complications of cardiac surgery

OBJECTIVE: To study the value of assaying cardiac troponin I (cTnI) for the early diagnosis of perioperative myocardial infarction (PMI) and various complications of cardiac surgery. DESIGN: A prospective observational clinical study. SETTING: Biochemical laboratory, anesthesia, and cardiac surgery department of H?pital Broussais. PATIENTS: Two hundred and sixty consecutive patients undergoing cardiac surgery. INTERVENTIONS: All patients underwent coronary artery bypass grafting and/or valvular surgery under extracorporeal circulation. Per-operative and postoperative follow-up consisted of electrocardiogram, echocardiography (mainly by the transesophageal approach), and serial determinations of biochemical markers such as creatinine kinase-MB isoenzyme (CK-MB) and cTnI. PMI, new ST segment changes, and ventricular arrhythmias were considered postoperative adverse cardiac outcome. MEASUREMENTS AND MAIN RESULTS: CTnI was measured before cardiopulmonary bypass (T0) and 12 and 24 hrs after (T12, T24). CK-MB was measured on arrival in the intensive care unit and on the first postoperative day (D1). Patients were divided into three groups according to the type of surgery: coronary artery bypass graft (CABG), valvular surgery (VS), or both procedures. The plasma CK-MB and cTnI concentrations were high in all patients after extracorporeal circulation because of aortic clamping or cardioplegia. The CK-MB and cTnI values were higher in the VS group than in the CABG group. Values peaked at T12 and fell by T24, except when PMI occurred. Eight patients developed a PMI. Patients with PMI had significantly higher cTnI levels at T12 and T24, and higher CK-MB values at D1 than patients without PMI. Cutoff values of cTnI for diagnosing PMI were >19 microg/L at T12 with 100% sensitivity and 73% specificity, and >36 microg/L at T24, with 100% sensitivity and 93% specificity. Lower cTnI values were highly suggestive of the absence of PMI after CABG and/or VS. Other complications such as ST segment changes, ventricular arrhythmias and cardiac failure were indicated by high cTnI levels at T12 and T24. Myocardial protective measures were associated with a nonsignificant increase in cTnI values. CONCLUSIONS: CTnI is more sensitive and specific than CK-MB for diagnosing PMI and other forms of heart failure after cardiac surgery.     

The value of serum CK-MB and myoglobin measurements for assessing perioperative myocardial infarction after cardiac surgery

In 41 patients who underwent coronary bypass surgery, creatine kinase (CK)-MB mass concentration was repeatedly measured in serum during and after the intervention using a new two-site immunoenzymetric assay (IEMA). Serum CK-MB activity was determined with the use of four different techniques: immunoinhibition, immunoinhibition-immunoprecipitation, column chromatography and electrophoresis. Myoglobin (Mb) was also measured in each specimen by radioimmunoassay. In the 33 patients who followed a completely uneventful postoperative course, the cumulated CK-MB release was, on the average, 12.2-fold less than after acute myocardial infarction. The CK-MB peak concentrations using the IEMA were 33 +/- 3 micrograms/l (X +/- SEM) and occurred 6.4 +/- 0.5 h after the intervention was started; CK-MB levels had decreased to 2.9 +/- 0.4 micrograms/l at the end of the first postoperative day. The evolution of the CK-MB concentration was parallel to that of the enzyme activity. The serum Mb maximum concentrations (518 +/- 39 micrograms/l) were reached after 3.3 +/- 0.1 h. The other eight patients developed perioperative myocardial infarction (PMI); in this group, the cumulated CK-MB release was higher, and the serum CK-MB postoperative curves were of three different types. The patients with delayed CK-MB peaks (type I pattern) or sustained elevations (type III) of this isoenzyme also showed increased serum Mb levels at the end of the first postoperative day. The PMI patients with early (10 h) CK-MB elevations (type II) did not demonstrate abnormal serum Mb levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two methods compared for measuring LD-1/total LD activity in serum

We present evidence for the utility of an improved assay for the activity of lactate dehydrogenase (EC 1.1.1.27) isoenzymes 1 and 2 in serum, involving inhibition of the H-subunit of LD by pyruvate at pH 7.1. Results correlate well with the LD-1/total LD ratio as evaluated by immunological assay and, as an index to infarct, the method is superior to either the change in CK-MB activity or to the LD-1 activity or to a combination of these tests, as is the percentage of LD-1 to total LD activity. Moreover, the percentage inhibition of LD activity by pyruvate may have an advantage over other methods of isoenzyme fractionation because of its smaller population CV for patients with acute myocardial infarction than is true of other methods. We also demonstrate how, using a linear discriminant analysis, we compared this method with alternative methods. We determined that evaluation of CK-MB isoenzyme contributes no information in addition to that obtained from the LD-1 isoenzyme.     

Activities of key enzymes in the energy metabolism of human myocardial and skeletal muscle

Summary. Activities of total creatine kinase (CK), its isoenzyme MB (CK-MB), total lactate dehydrogenase (LD) and its isoenzyme LD₁, phosphofructokinase (PFK), asparate aminotransferase (ASAT) and citrate synthase (CS) were determined in skeletal muscle biopsies obtained from physically trained and untrained men and in myocardial biopsies from patients subjected to open heart surgery because of valve disease. The LD₁, ASAT and CS activities were higher in trained than in untrained skeletal muscle and still higher in heart muscle than in either trained or untrained skeletal muscle. The CK-MB activity was higher in trained than untrained skeletal muscle and the myocardial CK-MB activity was similar to that in trained skeletal muscle. Total CK activity was slightly lower in trained than in untrained skeletal muscle and the myocardial CK activity was approximately one third of the skeletal muscle CK. Both the PFK and the total LD activity was of similar magnitude in the different muscle types. In conclusion, as estimated by enzyme activities, the oxidative capacity is 2–3 times larger in myocardial than in skeletal muscle, while the glycolytic capacity as estimated by PFK appears to be the same.     

Lactate dehydrogenase isoenzyme 1 as determined by inhibition with 1,6-hexanediol and by two other methods in patients with myocardial infarction or cardiac-bypass surgery

In this assay for lactate dehydrogenase (EC 1.1.1.27) isoenzyme 1 (LD-1), 1,6-hexanediol is added to serum after total LD has been measured. After incubation for 5 min the total LD remaining is determined. Samples from patients who had a myocardial infarction or who had undergone bypass surgery were assayed simultaneously by the 1,6-hexanediol method, the Roche "Isomune LD," and by electrophoresis on agarose gel. For 101 analyses of sera from bypass patients, correlations were high for results by the inhibitor method and electrophoresis (r = 0.96), by Roche Isomune and the inhibitor method (r = 0.96), and by the Roche method and electrophoresis (r = 0.97). In general, values for total LD were quite comparable by the three methods, but results by the inhibitor method seemed slightly higher and showed greater variability (CV) than those by the electrophoretic method. The assay is simple--requiring one reagent addition and a short incubation--and inexpensive: LD-1 can currently be determined for less than 1 over the cost of determining total LD.     

Lactate dehydrogenase isoenzyme 1: Its usefulness as a screening test in diagnosis of myocardial infarction

Immunological assay of LD-1 activity provides a quantitative measurement of the type of lactate dehydrogenase (LD, EC 1.1.1.27) activity characteristic of myocardial origin. Using this test, a laboratory diagnosis of myocardial infarction can be either ruled out or confirmed in approximately 75% of patients in whom this diagnosis is suspected, without electrophoretic separation of creatine kinase (CK, EC 2.7.3.2.) and LD isoenzymes. Normal total CK and LD activities cannot be used to rule out myocardial infarction since CK-MB and LD-1 may have increased although total activities remain within their reference ranges. LD-1 activity increases as quickly as CK-MB following the onset of pain in the majority of patients but it remains elevated longer giving a greater period of time during which the diagnosis of myocardial infarction can be confirmed.     

Lactate dehydrogenase isoenzyme-1/total ratio: accurate for determining the existence of myocardial infarction

We have gradually revised our medical protocols for measuring creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase isoenzyme-1 (LD-1) because of identifiable problems in the use of an interpretation of CK-MB isoenzyme associated with slowly evolving or small myocardial infarct, the use of thrombolytic therapy, or burn and trauma, each of which affects the rate of appearance and composition of isoenzymes present. Despite recent evidence of the efficacy of LD-1 isoenzyme measurement in the first 12 to 24 h of myocardial infarction, this test is not widely used because of overstated assumptions about the value of CK-MB. Here we studied the adequacy of the current isoenzyme assays by determining the value of CK-MB and LD-1 at optimum serum sampling times and establishing the contribution of individual and combined predictors to diagnostic efficiency. We conclude that the LD-1/total LD activity ratio in serum is superior to measurement of CK-MB or LD-1, or both, in the diagnosis of acute myocardial infarction. Moreover, this ratio is most valuable when interpretation of the result for CK-MB isoenzyme is equivocal in patients with small or evolving myocardial infarcts.     

An evaluation of the immunochemical LD-1 method in routine clinical practice

We report our extended clinical experience with the use of an immunochemical method for LD-1 assay in 260 unselected, consecutive patients admitted with the clinical suspicion of recent myocardial infarction (M.I.). We determined on every patient total creatine kinase (CK) and total lactate dehydrogenase (LD) enzyme activity, and performed electrophoresis for LD isoenzymes as well as the heart-specific band of creatine kinase (CK-MB). An immunochemical assay for the heart-specific isoenzyme of LD (LD-1) was also performed. The timing of the samples was determined by the clinicians according to routine clinical protocols in the coronary care units. The diagnosis was based on the usual combination of clinical, electrocardiographic (EKG) and laboratory findings, and was arrived at independently by the clinician. In this extended series, the overall efficiency of the immunochemical LD-1 assay for the proper classification of the patients according with the discharge diagnosis was 92%. For CK-MB it was 90%, for EKG 77% and for LD electrophoresis 76%. The immunochemical LD-1 assay required no special instruments or highly skilled technicians and is probably the method of choice for the stat evaluation of recent M.I.     

Influence of autoantibodies to creatine kinase-BB on assays for MB isoenzyme

We describe the influence of autoantibodies that bind creatine kinase BB (CK-BB) on the methods for MB isoenzyme. If these autoantibodies are present in patients' sera, they cause the formation of macro CK type 1 (immunoglobulin-linked CK-BB). In some of these cases they can bind not only endogenous CK-BB but also CK-MB without significantly affecting enzyme activity. Although these antibodies show distinctly less affinity for CK-MB than for CK-BB, they nevertheless bind CK-MB in these particular sera, because their concentration exceeds that of CK-BB isoenzyme. If a person with such autoantibodies has an acute myocardial infarction, the immunoinhibition method for CK-MB, which does not discriminate between CK-MB and CK-BB, will recognize the increase and peak of CK-MB with time, although persistent macro CK activity will be superimposed on the typical isoenzyme pattern. However, isoenzyme electrophoresis and recently introduced immunoenzymometric assays for CK-MB in these cases may be less sensitive for detecting myocardial infarctions, because the typical increase in CK-MB activity may be identified later in the progression of symptoms, or even be missed.     

Troponin T levels in detection of perioperative myocardial infarction after coronary artery bypass surgery

OBJECTIVES: The present study was designed to evaluate the clinical relevance of serum cardiac troponinT (cTnT) assay in detection of perioperative myocardial infarction (PMI) after coronary artery bypass grafting (CABG). MATERIALS AND METHODS: The clinical utility of cTnT was compared to that of total CK, CKMB mass, CKMB activity and myoglobin. Serial venous blood samples were obtained before surgery and 4, 8, 16, 24, 48 and 72 hours after aortic unclamping (AU) in 42 patients who underwent CABG. We had 6 PMI patients, 24 patients with minor myocardial damage (MMD) and 12 without ischemic myocardial changes (no IMC). RESULTS: In discriminating no IMC from PMI the diagnostic sensitivity, specificity and the predictive values of cTnT were superior to that of CKMB mass, CKMB activity, myoglobin and total CK during 72 hours after AU. In discriminating MMD from PMI the diagnostic performance for CKMB mass and CKMB activity was superior to that of cTnT during the first 24 hours. After 24 hours the diagnostic performance for cTnT was improved but began to decline for CKMB isoenzymes. The discriminatory power of myoglobin measurements was lower than that of cTnT and CKMB mass. CONCLUSION: Our results indicate that troponin T is an accurate marker for the detection and monitoring of perioperative myocardial damage, especially 24 hours after AU.     

Cardiac enzyme changes in myxedema coma

A 74-year-old man with myxedema and hypothermia had increased activities in plasma of creatine kinase (CK; EC 2.7.3.2), aspartate aminotransferase (AST; EC 2.6.1.1), and lactate dehydrogenase (LD; EC 1.1.1.27) and increased proportions of CK-MB (up to 20% of total CK) and LD1 isoenzymes, but no clinical or investigational evidence of associated myocardial infarction. This case illustrates that plasma enzyme activity and isoenzyme profiles in such clinical settings should be interpreted with caution, because increases in CK-MB and LD1 may relate to myxedema coma or hypothermia (or both) rather than to myocardial infarction.     

Activities of mitochondrial aspartate aminotransferase and creatine kinase isoenzyme MB in serum following coronary bypass surgery

The mitochondrial isoenzyme of aspartate aminotransferase showed only slight increases in serum of twenty-seven patients after uncomplicated coronary bypass surgery, which contrasted the rapid and substantial increases in creatine kinase MB. In seven patients suffering perioperative infarction or serious complications, substantial increases in mitochondrial aspartate aminotransferase were detected and the elevations in creatine kinase MB were prolonged. Mitochondrial aspartate aminotransferase may appear as a specific marker of myocardial necrosis following coronary bypass surgery. The elevations of creatine kinase and creatine kinase MB were detected as early as 5 minutes after onset of coronary reperfusion and slightly higher activities were measured in coronary sinus blood than in systemic blood sampled simultaneously. Increases in mitochondrial aspartate aminotransferase, however, could first be measured 8 hours after reperfusion.     

LD1 and several ratios of lactate dehydrogenase isoenzymes in acute myocardial infarction

The sensitivity and specificity of three parameters--ECG, creatine kinase MB isoenzyme and LD isoenzymes--were compared in 385 consecutive patients hospitalized for clinically suspected acute myocardial infarction (MI). In 147 patients acute MI was diagnosed on the basis of three parameters. In the remaining 238 patients acute MI was ruled out. Decision values for LD1, LD1/total LD, LD1/(LD2 + LD3 + LD4 + LD5), and the sum of LD1/LD2 + LD1/total LD + LD1/LD2 + LD3 + LD4 + LD5) were selected as 70 U/L, 0.33, 0.5, and 1.79, respectively for the test positivity of LD isoenzymes for acute MI. These new criteria, with the decision values, are proposed as test positivity of CK-MB and LD isoenzymes for acute myocardial infarction.     

Increased activities of creatine kinase and lactate dehydrogenase isoenzymes in a patient with metastatic ovarian tumor

A 50-year-old woman with metastatic rhabdomyosarcoma of the ovary had increased activities of creatine kinase (CK; EC 2.7.3.2), CK-MB isoenzyme, lactate dehydrogenase (LD; EC 1.1.1.27), and LD-2 isoenzyme in her serum. The isoenzyme activities did not show a pattern of increasing, then decreasing. Clinical findings, including electrocardiograms, did not support the diagnosis of myocardial infarction. We suggest that high activities of CK-MB and LD-2 in serum may serve as a marker of rhabdomyosarcoma.     

Relation of creatine kinase isoenzyme MB to postoperative electrocardiographic diagnosis in patients undergoing coronary-artery bypass surgery.

We compared (a) the frequency of detection of isoenzyme MB of creatine kinase (CK; EC 2.7.3.2) in serum of patients undergoing coronary-artery bypass surgery, (b) the interval during uhich its activity was supranormal in serum, and (c) an index of the amount of CK released into blood ("CK-MB area") with postoperative electrocardiographic changes in 80 patients. The frequency of detection of CK-MB is a function of frequency of sampling during the early postoperative period. Because the duration of appearance and the calculated CK-MB area increased as the electrocardiogram became more specific for infarction (p less than 0.01), a twice-daily sampling schedule proved clinically relevant. Only 5.4% of patients had electrocardiographic evidence of infarction when CK-MB was absent by the second postoperative morning. When CK-MB was still detected at that time, 69.6% of patients had persistent new Q waves, consistent with infarction. In three patients who died postoperatively, significant myocardial necrosis was demonstrated. All three had had persistently increased values for CK-MB, related to electrocardiographic changes of infarction in one patient and ischemic changes in two. Evidently CK-MB is a more sensitive indicator of myocardial necrosis than the electrocardiogram and CK-MB area should be a useful criterion in evaluating methods of intra-operative myocardial protection.     

Serum CK-MB isoenzyme after aortic and mitral valve replacements

A release of the MB fraction of creatine kinase (CK) enzyme into the serum due to myocardial manipulation and trauma occurs in patients undergoing cardiac surgery. Thus, the appearance of CK-MB activity as such is not sufficient to indicate of perioperative myocardial infarction. The mean (+/- SD) serum CK-MB isoenzyme level was 95 +/- 103 U/l 18 hours after aortic or mitral valve replacement in 76 patients. Thirteen patients undergoing closure of an atrial septal defect served as controls. They had a significantly lower (p less than 0.01) isoenzyme level postoperatively: 45 +/- 39 U/l. Two patients had the ECG changes of definite myocardial infarction after valve replacement and they also showed high CK-MB values, while the other patients with high enzyme level had no ECG signs suggesting acute infarction. CK-MB values correlated with the aortic cross-clamping time (r = 0.39, p less than 0.001) and weakly with the precordial ECG voltage of SV1 + RV5 (r = 0.25, p less than 0.01). While these findings may reflect the sensitivity of a thick myocardial wall to ischaemia during surgery, the postoperative recovery was not related to the serum CK-MB level.     

Clinical effectiveness of the Du Pont aca measurement of creatine kinase MB in serum from patients in a coronary-care unit

We evaluated the clinical effectiveness of measuring creatine kinase (CK; EC 2.7.3.2) isoenzyme MB and lactate dehydrogenase (LD; EC 1.1.1.27) isoenzymes in diagnosis of acute myocardial infarction. We used an agarose electrophoresis method to measure CK and LD isoenzymes and the Du Pont aca column method to measure CK-MB. Serial blood specimens were drawn from 100 patients consecutively admitted to our Coronary Care Unit. Because of the low diagnostic specificity for CK-MB measurements by both agarose electrophoresis and the discrete-analysis method, as compared with reported values, we re-evaluated our isoenzyme data by using Receiver Operating Characteristic curves. Such analysis of the data established optimal decision levels of greater than or equal to 25 U/L and greater than or equal to 18 U/L plus greater than or equal to 6% of total CK for serum CK-MB measured by the agarose electrophoresis and the aca methods, respectively, and an optimal decision level of greater than or equal to 0.92 for the ratio of LD 1/2 measured after agarose electrophoresis. At these decision levels we obtained a sensitivity of 100%, 100%, and 95% and a specificity of 94%, 92%, and 90% for CK-MB (agarose electrophoresis), CK-MB (aca), and the LD 1/2 ratio, respectively.     

Cytokine responses and myocardial injury in coronary artery bypass grafting

OBJECTIVE: Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery, and it may contribute to postoperative complications and even multiple organ dysfunction. We here compared the cytokine responses and the degree of myocardial injury after coronary artery bypass grafting with or without cardiopulmonary bypass. METHODS: Nine patients underwent off-pump revascularization and 13 with cardiopulmonary bypass. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-10 were measured before anesthesia induction, and 5 min, 1, 4, and 20 h after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were also measured after the operation. RESULTS: Levels of TNF-alpha were low in both groups. A delayed elevation of IL-6 was noted in the off-pump group. IL-8 and IL-10 levels were significantly higher in the CPB than in the off-pump patients after reperfusion (p=0.006 and 0.001 respectively). Postoperative CK-MB levels were significantly higher in the CPB than in the off-pump group (p=0.001). Cytokine levels correlated with CK-MB values. CONCLUSION: The results indicated that off-pump revascularization was associated with reduced cytokine responses and less severe myocardial injury. The degree of myocardial injury, as defined by CK-MB release, correlated with cytokine release. Intervention designed to reduce cytokine responses in cardiac surgery may be advantageous for patients with severe comorbidity.