Marker Of Myocardial Cell Injury Research Articles

Levels of Circulating Ketone Bodies in Patients Undergoing Cardiac Surgery on Cardiopulmonary Bypass.

Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a "driver" for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted.

A liquid-crystal-based immunosensor for the detection of cardiac troponin I.

Cardiac troponin I (cTnI) is one of the most sensitive and specific markers of myocardial cell injury, which can detect even minor myocardial damages. It is recognized as the main biochemical marker of the rapid diagnosis of acute myocardial infarction (AMI) and acute coronary syndrome (ACS). In this study, a label-free biosensor that utilizes the birefringence property of a nematic liquid crystal (LC) for the detection of cTnI is demonstrated. A chemically sensitive film with specific molecular recognition ability was decorated on the surface of a substrate, and the LC molecules were arranged in a vertically oriented order under the influence of the sensitive film, and a dark background signal was obtained using a polarizing optical microscope. When the antigen-antibody specifically binds to form a stronger acting force, the orientation of the LC molecules changes, resulting in a bright optical appearance. This LC-based immunosensor not only has the advantages of a facile structure, low cost and excellent specificity but also high sensitivity (a low detection limit of 1 pg ml-1), and has a promising future in biomedical related fields.

Circulating endothelial cells – a super-sensitive marker of myocardial cell injury

Circulating endothelial cells – a super-sensitive marker of myocardial cell injury

Evaluation of Patients With Acute Chest Pain of Uncertain Origin by Means of Serial Measurements of High-Sensitivity C-Reactive Protein

We investigated the usefulness of taking two serial measurements of the high-sensitivity C-reactive protein (hs-CRP) level for evaluating acute chest pain in patients with non-diagnostic ECG findings and normal levels of markers of myocardial cell injury (i.e., an inconclusive diagnosis). We hypothesized that the C-reactive protein concentration would be raised if symptoms were due to coronary endothelial damage or arteriosclerotic plaque rupture. The study involved 468 consecutive patients who presented to the emergency department with acute chest pain, 191 of whom had an inconclusive diagnosis. In this patient group, we determined the hs-CRP level on emergency admission and at 24 hours. Standard guidelines on managing acute chest pain of suspected coronary origin were followed. Any increase in hs-CRP level between baseline and 24 hours was regarded as a positive result. In total, 38 (20%) patients were diagnosed with chest pain due to coronary disease. Measurement of the hs-CRP level differential (i.e., the hs-CRP level at 24 hours minus the baseline level at emergency admission) had a sensitivity of 95% (95% confidence interval [CI] 81-98%), a specificity of 40% (95% CI, 32-47%), a positive likelihood ratio of 1.57 (95% CI, 1.33-1.83), a negative likelihood ratio of 0.13 (95% CI, 0.04-0.44), and an area under the receiver operating characteristic curve of 0.77 (95% CI, 0.69-0.85). By 30-day follow-up, no cardiac event had occurred in patients with a negative hs-CRP level differential. Measurement of the hs-CRP level differential is diagnostically useful in patients with acute chest pain of likely coronary origin. A negative result is associated with a low risk of ischemic heart disease and would allow patients to be discharged safely from the emergency department.

The clinical relevance of raised cardiac troponin I in the absence of significant angiographic coronary artery disease

Objectives Cardiac troponins are highly sensitive and specific markers of myocardial cell injury. We wished to determine the clinical relevance of raised troponins in the absence of significant angiographic coronary artery disease. Design and methods We assessed patients admitted to our hospital over the past 3 years with troponin-positive chest pain and no angiographically significant coronary disease. Results The study included 67 patients, all of whom had symptoms of “chest pain” and elevated (>0.2 μg/L) troponin I on admission. Thirty-four (51%) patients had alternative causes for myocyte injury other than coronary ischaemia. In the remaining 33 (49%) patients we could find no other associated features or diagnoses. Follow up was obtained in 29 (88%) of these 33 patients (mean follow up 58±13 weeks, range 17–156 weeks). During the follow up period, three (4.5%) patients were readmitted with further ischaemic events. Conclusions Myocardial damage can occur in the absence of significant angiographic coronary disease and other causes of raised troponins should be considered according to the clinical presentation. Troponin-positive cases with angiographically “normal” coronary arteries can re-present with future cardiac events and should still be considered for aggressive risk management.

Increases in serum levels of troponin I are associated with cardiac dysfunction and disease severity in pediatric patients with septic shock*

Myocardial cell injury may contribute to cardiac dysfunction in septic shock. Troponin I is a biochemical marker of myocardial cell injury and death. We hypothesized that troponin I is increased in pediatric patients with septic shock and correlates with cardiac dysfunction and disease severity. Prospective, observational study. Children's medical center. Twenty-three patients with septic shock and cardiovascular failure were enrolled. Serum troponin I was measured at admission and serially over 72 hrs. Within 24 hrs of study enrollment, echocardiograms were performed to determine left ventricular ejection fraction, systolic fractional shortening, heart rate corrected mean velocity of circumferential fiber shortening, and end-systolic wall stress. Requirement for inotropic support (stratified as low, moderate, or high), number of organ system failures, and other demographic data (including Pediatric Risk of Mortality III) were collected. Troponin I was increased on admission in 13 of 23 patients (57%) and at 12 hrs in ten of 22 patients (46%). In all cases, troponin I was maximal within 12 hrs of admission. Admission troponin I was inversely correlated to ejection fraction and fractional shortening and directly correlated to wall stress. Patients who had increased admission troponin I had lower heart rate corrected mean velocity of circumferential fiber shortening (preload and heart rate independent measure of left ventricular systolic function) and higher wall stress (measure of afterload) compared with patients with normal troponin I. Admission troponin I correlated with Pediatric Risk of Mortality III and organ system failure but did not correlate with requirement for inotropic support. Troponin I was increased in >50% of septic children early in their illness. Increased admission troponin I was associated with decreased measures of systolic cardiac function, as measured by echocardiography, and correlated with severity of illness. Early myocardial cell injury may contribute to the development of subsequent organ failure in septic shock, and measuring troponin I on admission may be helpful in assessing severity of sepsis.

Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure.

Cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell injury, is useful in diagnosing and assessing prognosis in acute coronary syndromes. Small studies report that cTnI is elevated in severe heart failure (HF) and may predict adverse outcomes. The present study evaluated 238 patients with advanced HF referred for cardiac transplantation evaluation who had cTnI assay drawn at the time of initial presentation. Patients with acute myocardial infarction or myocarditis were excluded from analysis. cTnI was detectable (cTnI > or =0.04 ng/mL) in serum of 117 patients (49.1%). Patients with detectable cTnI levels had significantly higher B-type natriuretic peptide (BNP) levels (P<0.001) and more impaired hemodynamic profiles, including higher pulmonary wedge pressures (P=0.002) and lower cardiac indexes (P<0.0001). A significant correlation was found between detectable cTnI and progressive decline in ejection fraction over time. Furthermore, detectable cTnI was associated with increased mortality risk (RR, 2.05; 95% CI, 1.22 to 3.43). After adjustment for other factors associated with adverse prognosis including age, sex, ejection fraction, and coronary artery disease, cTnI remained a significant predictor of death. cTnI used in conjunction with BNP further improved prognostic value. cTnI is associated with impaired hemodynamics, elevated BNP levels, and progressive left ventricular dysfunction in patients with HF. cTnI may be a novel, useful tool in identifying patients with HF who are at increased risk for progressive ventricular dysfunction and death.

Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings

Background: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. Methods: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access® (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. Results: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group ( p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline ( p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls ( p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW ( r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. Conclusions: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.

Metabolic changes and myocardial injury during cardioplegia: a pilot study

Background. The timing, nature, and severity of both increased cardiac troponin I (cTn-I) levels and myocardial injury during ischemic arrest with cardioplegia are unknown. To define them more accurately, we studied myocardial metabolic activity and the release of markers of myocardial cell injury into the coronary sinus before, during, and after cardioplegia. Methods. We simultaneously measured creatine kinase, creatine kinase-MB, cTn-I, lactate, phosphate, and blood gases in coronary sinus and systemic arterial blood from 12 patients before cardiopulmonary bypass, after removal of the aortic cross-clamp, and after discontinuation of cardiopulmonary bypass. We also measured coronary sinus flow and transmyocardial fluxes of all analytes and calculated myocardial oxygen consumption, myocardial carbon dioxide production, and myocardial energy expenditure. Results. Myocardial lactate release increased 10-fold after removal of the aortic cross-clamp ( p = 0.012) and was accompanied by a surge in myocardial phosphate uptake ( p = 0.056). These events were associated with only partial cardioplegia-induced suppression of myocardial oxygen consumption ( p = 0.0047), myocardial carbon dioxide production ( p = 0.0022), and myocardial energy expenditure ( p = 0.0029). Simultaneously, coronary sinus cTn-I levels increased from a mean of 0.76 to 2.43 ng/mL after removal of the aortic cross-clamp, and 2.51 ng/mL after cardiopulmonary bypass ( p = 0.014), leading to an increase in arterial cTn-I concentration from 0.18 to 0.98 and 3.01 ng/mL ( p = 0.0002). Thus, cTn-I release across the myocardium was absent at baseline, became detectable ( p = 0.012) after removal of the aortic cross-clamp, and correlated with cross-clamp and pump times. Similar changes occurred with creatine kinase-MB. Conclusions. Metabolic myocardial stress occurs during ischemic arrest with cardioplegia and is associated with inadequate suppression of metabolism and with a surge in cTn-I and creatine kinase-MB release, which is maximal after removal of the aortic cross-clamp. These changes are likely to represent structural myocardial cell injury.

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access ®) and cTnT (Elecsys ®) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean±S.D., 1.1±2.3 ng/ml) and cTnT (mean±S.D. 3.6±30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0–6 h) and the maximal cTnI and cTnT (0–6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered ( P=0.08) and for LD AUC (0–6 h) ( P=0.059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 ( P=0.0001) and 0.60 ( P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

Perioperative myocardial cell injury: The relationship between troponin t and cortisol

Study Objective: To investigate whether there is an association between Troponin T (TnT), reflecting myocardial cell injury, and cortisol, reflecting the degree of surgical trauma and associated stress, in light of our recent evaluation of TnT as a marker of perioperative myocardial cell injury. Design: Prospective, cohort study. Patients: 70 patients (67.4 ± 8.7 yrs) with definite or at-risk coronary artery disease (CAD) undergoing elective noncardiac surgery (vascular n = 38, abdominal n = 21, orthopedic n = 8) with general (n = 63) or regional (n = 4) anesthesia with postoperative on-demand analgesia. Measurements and Main Results: Morning blood samples for TnT (upper limit of normal: <0.2 ng/mL), CK-MB (reference range ≤12 U/L), and cortisol (normal morning range 7–25 μg/dL) were taken on the day before surgery, on the morning of surgery before induction of anesthesia, and on the first 5 postoperative days. Data were compared by analysis of variance. Three patients were excluded from the study because of incomplete blood samples of TnT or cortisol. Preoperative mean cortisol levels (μg/dL ± SD) were within the normal range and equal in TnT positive (n = 13) and negative (n = 54) patients (16.1 ± 4.5 vs. 15.6 ± 5.8). On the 1st postoperative day, there was a substantial increase of cortisol in the TnT positive group (35.7 ± 26.9). Cortisol remained high until the 5th postoperative day (24.7 ± 9.4). There was a significant difference in the cortisol concentration in TnT-positive compared to TnT-negative patients (p < 0.001), a significant difference in the perioperative cortisol concentration over time (p < 0.05), and a significant interaction (p < 0.001). But there was no consistent temporal relationship between the increase of TnT and the increase of cortisol. Conclusions: The significant relationship between a highly sensitive and specific marker of myocardial cell injury and a marker of stress suggests that cardiac-risk patients undergoing stressful surgical procedures might benefit from close perioperative TnT monitoring with early recognition of myocardial cell injury.

Plasma Troponin T and Troponin I after Minimally Invasive Coronary Bypass Surgery

In the last decade, plasma cardiac troponin T (cTnT) and cardiac troponin I (cTnI) have been identified as specific and sensitive markers of myocardial cell injury (1)(2). During most types of cardiac surgery, some degree of myocardial injury regularly occurs that is dependent on multiple factors, such as the type and extent of the surgical procedure, the method of myocardial protection, the preoperative cardiac status of the patient, and the anesthetic procedures (3)(4). In recent years, minimally invasive direct coronary artery bypass grafting (MIDCAB) and off-pump coronary artery bypass grafting (OPCAB) have been introduced as alternative methods to coronary artery bypass grafting (CABG) (5). The potential advantages of MIDCAB and OPCAB arise from the avoidance of cardiopulmonary bypass (CPB) and cardioplegia. CPB always induces a systemic inflammatory response syndrome, and a substantial number of patients develop multiple organ dysfunction. However, there are also disadvantages of MIDCAB and OPCAB, including difficulty of performing the coronary anastomosis on the beating heart, ischemic damage during occlusion of the targeted vessel, and cardiac dislocation or compression to obtain optimal exposure of the vessels on the posterior wall. Currently, only limited data (6)(7)(8)(9) concerning the release of troponins during MIDCAB …

QT interval dispersion: non-invasive marker of ischemic injury in patients with unstable angina pectoris?

Prognostic assessment of unstable angina pectoris is a common clinical problem for physicians. Markers of myocardial cell injury, serial electrocardiographic findings and ST segment monitoring are mainly studied for prognosis. We investigated the relation between myocardial injury and the value of cardiac troponin T and QT interval dispersion in hospitalized unstable angina patients. This is a prospective study that includes adult patients admitted to an emergency department with Braunwald class IIIB unstable angina pectoris. Eighty-six patients were enrolled in the study (mean age of 57 +/- 12 years, 63 males and 23 females). Cardiac troponin T was assayed and QT dispersion calculated from surface ECG. Fifty-eight patients with troponin T < 0.1 ng/ml and 28 patients with troponin T levels > or = 0.1 formed group 1 and group 2, respectively. There were no significant differences in sex, age, history of coronary revascularization or ECG findings such as ST depression and T inversions between the two groups. The QT dispersion was significantly greater in patients with elevated cardiac troponin T levels (77 +/- 18 msec vs 38 +/- 13 mse; p < 0.014). Because QT interval dispersion exhibited an association with cardiac troponin T levels, it may be used as a non-invasive marker of ischemic injury in patients with unstable angina.

Release kinetics of cardiac troponin I and cardiac troponin T in effluents from isolated perfused rabbit hearts after graded experimental myocardial contusion.

Few experimental studies report effects of direct contusion on cardiac enzyme release. Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. This investigation was designed to determine and compare the acute effects of quantified magnitudes of blunt cardiac trauma upon release of cTnI and cTnT in comparison with creatine kinase (CK) and lactate dehydrogenase (LD). In 24 rabbit hearts prepared on a standard Langendorff apparatus, myocardial contusion (MC) was produced by a single blow with a ball falling from a predefined height, delivered directly to the surface of the heart. Hearts were divided into control (n = 6) and various quantified impacts: 75 mJoules (mJ) (n = 6), 100 mJ (n = 6), 200 mJ (n = 6). Coronary effluent samples for cTnI, cTnT, CK, and LD were collected at baseline, immediately after MC and 5, 15, 30, 45, and 60 minutes after MC. At the end of experiment, histologic condition was evaluated. The anti-cTnI and cTnT MAbs used in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rabbit. The time-courses of cTnI, cTnT, CK, and LD were monophasic in form. After MC, all parameters rose significantly compared with baseline and with control group. The maximal release occurred immediately after MC. The area under the cTnI curve and the maximal cTnI concentration were linked to the contusion energy when increased at 200 mJ. Maximal concentrations and areas under cTnT, CK, LD time activity curve were not linked to the contusion energy level and showed no between-energy group differences. The correlation found between maximal cTnI and maximal cTnT concentrations was 0.70 (p = 0.0001). Histologic examination showed cellular disruption and after the more severe impact, the extent of pathologic changes was more extensive. After graded experimental MC, maximal cTnI concentration and area under cTnI curve increase with the power of impact kinetic energy. Levels of cTnI allow a much higher accuracy in detecting the extent of myocardial injury postMC in comparison with cTnT, CK, and LD in this experimental study. These results should be consistent with the more extensive cTnI release with more severe impact in patients with blunt chest trauma. Furthermore, because specificity and time-course of release, both cTnI and cTnT should have a role in the diagnosis and evaluation of such patients.

Circulating Cardiac Troponin T in Myocardial Contusion

Myocardial contusion may induce life-threatening complications, but its diagnosis is difficult. Circulating cardiac troponin T is considered a highly sensitive and specific marker of myocardial cell injury. We investigate the value of cardiac troponin T measurement in the diagnosis of myocardial contusion. Prospective study. Level 1 trauma center. We prospectively measured circulating cardiac troponin T and performed echocardiography and continuous Holter monitoring in patients who had suffered blunt trauma. Myocardial contusion was diagnosed in patients who fulfilled one of the following criteria: (1) an abnormal echocardiography compatible with myocardial contusion; (2) severe cardiac rhythm abnormalities; (3) severe cardiac conduction abnormalities; and (4) hemopericardium. One hundred twenty-eight patients were included and myocardial contusion was diagnosed in 29 patients. Patients with myocardial contusion had more severe trauma, experienced more frequently associated thoracic lesions, and had a lower left ventricular ejection fraction area (48 +/- 15 vs 61 +/- 10%; p < 0.001). Elevated circulating cardiac troponin T concentrations were significantly more frequent in patients with a myocardial contusion (31 vs 9%; p < 0.007). An elevated circulating cardiac troponin T concentration (> or = 0.5 microgram/L) was more accurate than MB fraction of creatine kinase (CK) (CK-MB) and CK-MB/CK ratio in the diagnosis of myocardial contusion, as shown by an area under the receiver operating characteristic (ROC) curve (AROC), which was significantly different from 0.50 (AROC = 0.69; 95% confidence interval, 0.56 to 0.80). However, this improvement was not clinically acceptable (sensitivity, 0.31; specificity, 0.91). Circulating cardiac troponin T measurement had a slightly greater diagnostic value than usual biological parameters (CK-MB, CK-MB/CK) in myocardial contusion. Nevertheless, it was concluded that an elevated circulating cardiac troponin T concentration has no important clinical value in the diagnosis of myocardial contusion.

Serum Cardiac Troponin T and Creatine Kinase–MB Elevations in Murine Autoimmune Myocarditis

We used a murine model of autoimmune myocarditis to investigate systematically whether serum markers of myocardial cell injury, that is, cardiac troponin T (TnT) and the MB isoenzyme of creatine kinase (CK-MB) are useful for the diagnosis of inflammatory heart disease. Fifty-two A.SW mice were immunized with cardiac myosin to induce myocarditis. The disease was evident on day 12 after the initial immunization in 14 of 22 immunized mice, on day 16 in 7 of 10 mice, on day 19 in 6 of 10 mice, and on day 23 in 5 of 10. The severity of myocarditis increased between days 12 and 16 and remained constant thereafter. TnT was elevated in a considerable number of mice with myocarditis, resulting in a diagnostic sensitivity (number of marker elevations per number of mice with myocarditis) of 0.43 on day 12, 0.71 on day 16, and 0.50 on day 19. CK-MB elevations were not seen on day 12 but resulted in a diagnostic sensitivity of 0.71 on day 16 and of 0.33 on day 19. No elevations of CK-MB or TnT were observed on day 23. All elevations were specific for the disease, as none of the mice lacking myocarditis showed increased markers. In murine autoimmune myocarditis, TnT is a more sensitive marker for the disease than CK-MB. Elevations clearly indicate myocarditis, but negative test results do not exclude the presence of the disease. These data suggest that the determination of CK-MB and, in particular, of TnT, can be useful for the diagnostic evaluation of patients with suspected myocarditis.

Circulating Cardiac Troponin T in Potential Heart Transplant Donors

Brain death may induce myocardial dysfunction, the mechanisms of which are not yet fully understood. Circulating cardiac troponin T is considered a highly sensitive and specific marker of myocardial cell injury. We prospectively measured circulating cardiac troponin T in 100 brain-dead patients and measured the left ventricular ejection fraction area (LVEFa), using transesophageal echocardiography. Sixty-one patients had normal LVEFa, 25 had moderate decrease in LVEFa (30% to 50%), and 14 had severe decrease in LVEFa (< or = 30%). Circulating cardiac troponin T concentrations were significantly higher (1.68 +/- 1.03 micrograms/L-1, P < .01) in patients with a severe decrease in LVEFa than in the two other groups (0.42 +/- 0.43 and 0.12 +/- 0.16 microgram/L-1, respectively), and there was a significant correlation between LVEFa and cardiac troponin T concentration (p = -0.59, P < .0001). An elevated circulating cardiac troponin T concentration (> or = 0.5 microgram/L-1) was more accurate (sensitivity, 1.00; specificity, 0.84) in predicting a severe decrease in LVEFa than an elevated CKMB value or an increased CKMB/CK ratio. An elevated circulating cardiac troponin T was associated with a severe decrease in LVEFa in brain-dead patients, suggesting that severe and potentially irreversible myocardial cell damage occurred. In contrast, CKMB determination was not useful. Since the quality of the donor's heart is considered an important prognosis factor in heart transplantation, the determination of circulating cardiac troponin T concentration could be useful to the heart transplantation team.

Creatine kinase MB isoforms: sensitive markers of ischemic myocardial damage

We investigated the use of creatine kinase (CK) MB isoforms as a marker of myocardial cell injury in a preliminary study of 16 patients with chronic stable angina after successful percutaneous transluminal coronary angioplasty (PTCA) and 25 patients after coronary artery bypass grafting (CABG). Three control groups were studied: apparently healthy volunteers (n = 31), patients undergoing thoracotomy (n = 10), and patients undergoing routine coronary angiography (n = 9). Patients in the PTCA group showed an association between ischemic ST segment changes lasting > 3 min and a transient increase in the MB2/MB1 ratio; however, all had total CK-MB activity within normal limits. Routine coronary angiography subjects had no significant change in MB2/MB1. In the CABG patients, MB2/MB1 peaked within 1 h after the cross-clamp release and returned to baseline by 24 h postoperatively. The median time to peak MM3/MM1 and total CK-MB activity was 2 and 8 h after reperfusion, respectively, returning to baseline values by 2 and 5 days, respectively. After thoracotomy, MB2/MB1 was increased only in elderly patients (n = 5) with risk factors for ischemic heart disease; total CK-MB activity was increased in only three of these. Apparently, CK-MB isoforms can detect myocardial damage in clinical settings with less overt damage than myocardial infarction.

The leakage of fatty acid binding protein from cultured myocardial cells during hypoxia

Fatty-acid binding protein (FABP) is thought to play an important role as a carrier protein of fatty acids in cells. It may leak from damaged cells, because its molecular weight is low (mol wt 14000) and it accounts for several percent of soluble protein. In this experiment we attempted to use FABP as a marker of cell injury under hypoxia in cultured myocytes. Newborn-rat myocytes were incubated under hypoxic treatment for 6 hours, and then the releases of FABP and CPK were measured. The cell-death ratio during hypoxygenation increased from 4 hours and rose to 80% at 6 hours, but it was only 8% under aerobic conditions. FABP in medium was detected at 1 hour, and rapidly increased and reached a plateau at 4 hours. On the other hand, CPK in medium was negligible during the 3 hours, then slightly increased. Ca antagonists and a beta 1-adrenergic blocking agent inhibited the release of FABP and prevented cell death. But the alpha 1-adrenergic blocking agent had little effect on preventing FABP leakage and cell death. These results show that FABP is of use as a marker of myocardial cell injury and revealed that the Ca antagonist and beta 1-adrenergic blocking agent are useful drugs for the protection of myocardial cell injury in hypoxia.