A controlled trial of substrate-enhanced, warm reperfusion ("hot shot") versus simple reperfusion.

BACKGROUND: Modified reperfusion after aortic cross-clamping is claimed to reduce myocardial injury, thus improving postoperative myocardial performance. METHODS: We measured perioperative release of creatine kinase-MB and troponin-T in 40 patients undergoing valve replacement (combined with coronary grafts in 12 cases) to determine whether infusion of a modified reperfusate before cross-clamp removal reduced myocardial injury. Patients were randomly allocated to one of two groups with minimization for age, surgeon, operation, and ventricular function. The control group received unmodified reperfusion, while the study group received a normothermic reperfusate, enhanced with glutamate and aspartate, for 5 minutes before removal of the cross-clamp. Serial determinations of troponin-T, creatine kinase-MB isoforms, and total creatine kinase-MB activity were made up to 5 days postoperatively. Requirements for inotropic support and evidence of myocardial infarction were documented. RESULTS: Creatine kinase-MB activity, creatine kinase-MB isoforms, and troponin-T were not significantly different between the two groups. There were no differences in the incidence of postoperative myocardial infarction or in inotrope requirement. CONCLUSIONS: Our study did not demonstrate any advantage in using modified reperfusion in this group of patients.

Serum sialic acid concentration is not associated with the extent or severity of coronary artery disease in patients with stable angina pectoris.

BACKGROUND: Total serum sialic acid concentration has been reported to predict death from cardiovascular disease. This study was performed to assess the relation between serum sialic acid concentration and the angiographic extent and severity of coronary atheroma in patients with stable angina. METHODS: Quantitative coronary angiography was performed in 40 patients with stable angina with either triple-vessel disease (23 patients) or normal/nearly normal coronary arteries (17 patients). A colorimetric assay for the enzymatic determination of serum sialic acid was used. RESULTS: Serum sialic acid concentration was not significantly different in patients with normal or nearly normal coronary angiograms compared with those with triple-vessel disease (68+/-10 mg/100 mL and 68+/-11 mg/100 mL, respectively). Neither was there any association between the extent or severity of coronary disease and serum sialic acid levels. CONCLUSIONS: Serum sialic acid concentration does not appear to be associated with the extent or severity of coronary artery disease in patients with stable angina pectoris. Thus the previously described association between serum sialic acid and cardiovascular death may reflect the role of mechanisms other than the severity of coronary artery narrowings.

Myocardial injury induced by radiofrequency and low energy ablation: a quantitative study of CK isoforms, CK-MB, and troponin-T concentrations.

We conducted a prospective, controlled study to investigate the use of CK-MB concentration and newer methods such as troponin-T concentration and CK isoforms, in the assessment of myocardial damage caused by radiofrequency current or low energy DC catheter ablation. The study population consisted of 3 consecutive patients who underwent low energy catheter ablation, 28 consecutive patients subjected to radiofrequency ablation, and 4 patients who were subjected to radiofrequency energy ablation but also had external DC shocks for cardioversion of atrial fibrillation that occurred during the procedure. The control group comprised eight subjects undergoing electrophysiological study. Prior to ablation and at 30 minutes, 1, 2, 6, and 12 hours following the procedure, serial blood samples were taken for measurement of troponin-T and CK-MB concentrations, and calculation of the MM3/MM1 and MB2/MB1 ratios. Troponin-T concentration was raised above normal in all patients subjected to low energy ablation and in all but two patients subjected to radiofrequency ablation. Only 42% of all patients subjected to ablation had at least one raised CK-MB concentration postablation. The MB2/MB1 ratio was raised in all but had at least one raised CK-MB concentration postablation. The MB2/MB1 ratio was raised in all but two patients following radiofrequency or low energy ablation but it was also abnormal in the preablation samples in nine patients. The MM3/MM1 ratio failed to detect myocardial damage in 71% of all patients. There was a statistically significant difference between the control and patient groups regarding all four indices of myocardial damage. Low energy ablation caused a significantly higher degree of myocardial damage compared with radiofrequency (RF); this effect could not be attributed to different numbers of total energy discharges. Our results indicate that catheter ablation, regardless of the mode of energy used, inflicts detectable injury upon the myocardium. This injury can be quantitated by using newer analytical techniques, such as serial, postablation measurements of troponin-T concentration.

Use of troponin-T concentration and kinase isoforms for quantitation of myocardial injury induced by radiofrequency catheter ablation.

BACKGROUND: Although there remains particular concern about late malignant ventricular arrhythmias arising from myocardial damage induced by catheter ablation, the extent of myocardial injury resulting from clinical ablation procedures has not been fully studied. We conducted a prospective, controlled study to investigate the use of two newer markers of myocardial integrity, troponin-T concentration and creatine kinase isoforms, and a traditional marker, creatine kinase-MB concentration, in the assessment of myocardial injury following radiofrequency catheter ablation. METHODS AND RESULTS: The study population consisted of 28 consecutive patients subjected to radiofrequency catheter ablation, and the control group comprised eight subjects undergoing diagnostic electrophysiology study. Prior to ablation and at 30 min, 1, 2, 6, and 12 h following the procedure, blood samples were taken to measure troponin-T and creatine kinase-MB concentrations, and the separation of creatine kinase isoforms (MM3/MM1 and MB2/MB1 ratios). The troponin-T concentration was above normal in all but two patients following radiofrequency ablation, and the MB2/MB1 ratio was raised in all but one patient following ablation, but was also abnormal in the pre-ablation samples in seven patients. The MM3/MM1 ratio failed to detect myocardial injury in 75% of patients. Of patients subjected to ablation, in only 36% was the creatine kinase-MB concentration raised at least once post-ablation. Thirty minutes post-ablation, there was a statistically significant difference between the control and patient groups only as regards troponin-T concentration. There was a significant association between troponin-T concentration immediately post-procedure, the number of discharges delivered (r = 0.52, P = 0.006) and maximum power used (r = 0.48, P = 0.009). CONCLUSION: Our results indicate that catheter ablation inflicts a cumulative, detectable injury upon the myocardium. This injury can be quantitated by using newer analytical techniques, such as serial, post-ablation measurements of troponin-T concentration.

Creatine kinase isoforms as circulating markers of deterioration in idiopathic dilated cardiomyopathy.

BACKGROUND: A proportion of patients with dilated cardiomyopathy (DCM) may have ongoing myocardial damage secondary to viral or immune mediated myocardial inflammation. HYPOTHESIS: The prognostic determinants identify patients with decreased survival but do not provide a measure of myocardial damage. To obtain an objective assessment of myocardial damage in DCM, we measured plasma levels of creatine kinase (CK), its isoenzymes (CK-MM and CK-MB), and separated the isoforms of CK-MM and CK-MB. METHODS: The cohort consisted of 77 consecutive patients (61 men, 16 women) with DCM (World Health Organization criteria), aged 49 +/- 14 years (range 19-60). Patients had been symptomatic for 29 +/- 38 months (range 0.5-200 months) with 48 in New York Heart Association class I/II and 29 in class III/IV at the time of diagnosis. During median follow-up of 27 months from diagnosis (range 0.6-165), 50 patients remained clinically stable and 27 had deteriorated. RESULTS: A significantly higher proportion of patients with DCM had abnormal MB2/MB1 ratio compared with normal volunteers (11, 14% vs. 1,1%, p = 0.003). Patients who deteriorated had higher MB2/MB1 ratio, (1.22 +/- 0.62 vs. 0.85 +/- 0.56; p = 0.01), and more frequently had abnormal MB2/ MB1 ratio (8, 30% vs. 3, 6%; p = 0.004) and CK and CK-MM activities (5, 19% vs. 2, 4%; p = 0.03) than those who remained stable. Patients with DCM with high CK-MB activity had 3.13-fold increased odds of sudden death or need for cardiac transplantation (95% confidence interval 1.53-6.40, p = 0.008). Thus, CK measurements, in particular CK-MB isoforms, are markers of myocardial damage in a subset of patients with DCM and could be useful in investigating the possibility of persistent myocardial damage in these patients.

[The diagnosis of myocardial damage during coronary angioplasty by the analysis of the isoforms of the enzyme creatine kinase MB]. / Diagnóstico de daño miocárdico durante la angioplastia coronaria mediante el análisis de las isoformas de la enzima creatincinasa MB.

BACKGROUND: The existence of myocardial damage during percutaneous transluminal coronary angioplasty (PTCA) is controversial. Mild elevations in creatine kinase (CK) activity and its isoenzyme MB (CKMB) in patients who underwent PTCA have been reported. However, other authors failed to confirm these elevations. The low sensitivity of total CK and CKMB activity for the detection of myocardial damage in different settings other than myocardial infarction might account for the controversial findings. Measurement of CKMB isoforms has been shown to have a higher sensitivity than the assessment of CK or CKMB activity for early diagnosis of myocardial infarction. Its sensitivity for the diagnosis of myocardial damage in settings other than infarction is not well described. OBJECTIVES: The aim of our study was two-fold: 1) to assess the incidence of myocardial damage after PTCA and 2) to compare the sensitivity of total CK and CKMB activity and measurement of CKMB isoforms for the detection of myocardial damage. METHODS: 14 patients (11 men and 3 women) with chronic stable angina underwent PTCA. Two electrocardiographic leads were monitored from the beginning of the procedure until 30 minutes after the PTCA. ST segment shifts of at least 1 mm, lasting for more than 1 minute, were considered indicative of myocardial ischemia. The duration of ischemic episodes was measured from the onset of the ST shift until its return to baseline. Total ischemic time, in minutes, was the sum of the duration of every ischemic episode. Blood samples were drawn before PTCA and serially during the first 24 hours post PTCA. CK (normal < 200 U/l) and CKMB (normal < 14 U/l) activities were measured. The CKMB isoforms were separated by electrophoresis, measured by densitometric scanning and their ratio calculated (CKMB2/CKMB1 normal < 1.5). RESULTS: Vessels which underwent PTCA were: the left anterior descending artery (LDA) in 5 patients, the circumflex coronary artery (Cx) in 3 patients, right coronary artery (RCA) in 3 patients, LDA and Cx in 1 patient and Cx and RCA in 2 cases. Eleven patients underwent balloon dilatation, 1 underwent atherectomy (Rotablator) and two patients had treatment with both Rotablator and balloon angioplasty. Ischemic ST segment shifts were found in ten patients and the median of total ischemic time was 13.5 minutes (interquartile range: 2-15 minutes). Total CK and CKMB activities were within the normal range in every patient whereas in 7 patients (50%) the peak ratio CKMB2/CKMB1 was above the normal range. There were no differences in age, sex, number of vessels or lesions treated or in the time of balloon inflation between patients with and without abnormal CKMB2/CKMB1 peak. However, the ischemic time was significantly higher in patients with CKMB2/CKMB1 > 1.5 (median 15 vs 0 minutes; p = 0.023). CONCLUSIONS: Myocardial damage during PTCA is not an uncommon finding. The CKMB isoforms are more sensitive markers of myocardial damage during PTCA than total CK or CKMB activities.

Creatine kinase MB isoforms: a potential predictor of acute cardiac allograft rejection.

BACKGROUND: Noninvasive studies to detect or predict acute allograft rejection after heart transplantation have failed to be sufficiently reliable to substitute for endomyocardial biopsy. Isoforms of creatine kinase MB isoenzyme (MB2 and MB1) are extremely sensitive markers of ischemic myocardial damage and, in theory, may be elevated in cardiac allograft rejection when myocardial necrosis is visible on microscopy (International Society for Heart and Lung Transplantation grade 2 or greater). METHODS: We examined, prospectively, the endomyocardial biopsy specimens (n = 256) of 50 consecutive patients undergoing orthotopic heart transplantation. Blood samples for creatine kinase MB isoforms (n = 527) were taken immediately before endomyocardial biopsy and at intervals between biopsies. RESULTS: The median ratio of MB2/MB1 in plasma samples taken at the time of biopsy for grades 2 and 3 was not significantly different from the ratio from biopsy specimens graded 0 and 1 (1.65 versus 1.33; p = Not significant). The sensitivity for diagnosing a moderately severe rejection was 47% with a specificity of 58%. However, in patients with significant acute rejection (grades 2 and 3) in whom consecutive samples were collected, the MB2/MB1 ratio was significantly increased before histologic changes seen on biopsy in 13 of 16 rejection episodes by a mean of 14 days. The sensitivity for predicting rejection (grade 2 or 3) before endomyocardial biopsy was 60% with a specificity of 71% (positive predictive value 43%, negative predictive value 86%). CONCLUSIONS: Creatine kinase MB isoforms may predict the occurrence of acute rejection before histologic evidence seen on endomyocardial biopsy.

Comparison of two strategies for myocardial management during coronary artery operations.

Despite the current trend for using blood cardioplegia, ventricular fibrillation with intermittent ischemia is still used as a strategy to manage the myocardium with impressive results. These two methods of myocardial management were compared in 40 patients undergoing elective coronary artery operations using creatine kinase MB isoforms and troponin T assays. Each patient was randomized to have either cold blood cardioplegia (n = 20) or ventricular fibrillation with intermittent ischemia (n = 20) for myocardial management during the construction of distal anastomoses. Until recently, the comparison of different methods of myocardial management has been hindered by the lack of a specific and sensitive marker of myocardial damage. Analysis of creatine kinase MB isoforms (MB2, cardiac tissue form; MB1, plasma-modified form) and cardiac-specific troponin T (a structural protein) has been shown to improve the sensitivity for the detection of myocardial damage. There were no significant differences between the two groups in age, sex ratio, extent of disease, or left ventricular function. Blood samples for analysis were collected before cross-clamp application and at time intervals up to 48 hours after. Median peak creatine kinase MB2 activity was found to be significantly higher in the blood cardioplegia group compared with ventricular fibrillation (26.5 U/L versus 19.5 U/L, respectively, p = 0.04). Although median peak troponin T concentration was higher in the blood cardioplegia group, the difference failed to reach significance (2.2 ng/mL versus 1.6 ng/mL, p = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Urinary protein excretion and the diagnosis of graft rejection or renal dysfunction in renal transplant patients.

Urinary proteins have been found to be a sensitive marker of renal damage caused by nephrotoxic agents. An electrophoretic method was used to investigate the potential value of the pattern of urinary protein excretion in 14 cyclosporin-treated renal transplant patients, to differentiate between graft rejection episodes and other causes of renal dysfunction. Urinary protein excretion consistent with renal damage was observed in all of the patients studied, with no marked differences between those with signs of graft rejection, those with renal dysfunction, or those with stable renal function.

Radioimmunoassays for spirapril and its active metabolite spiraprilate: performance and application.

Radioimmunoassays for a nonsulfhydryl angiotensin converting enzyme inhibitor prodrug--spirapril--and its active metabolite--spiraprilate--are described. Nonextraction equilibrium assays using antibodies with a high specificity for spirapril or spiraprilate were used, with charcoal separation of bound and free tracer. Within-assay reproducibility (CV%) was less than 20% in the concentration range 0.5-40 micrograms/L for both analytes and the comparable value for between-assay reproducibility was less than 25%. Results for external quality control samples were in good agreement with the expected values of 0-250 micrograms/L (spirapril, r = 0.997) and 0-300 micrograms/L (spiraprilate, r = 0.999). Overall, samples circulated to four laboratories gave good agreement for measured values, including one center using gas chromatography-mass spectrometry analysis for the two compounds. Data are presented to show the suitability of these two assays to the measurement of spirapril and spiraprilate in clinical samples from assays to the measurement of spirapril and spiraprilate in clinical samples from dose-ranging and bioequivalence studies. Results are also shown relating drug plasma concentration data to a measurement of the pharmacodynamic effects of spiraprilate, namely inhibition of angiotensin converting enzyme activity. It is concluded that these assays have the sensitivity for use in studies to model the relationship between the pharmacokinetics and pharmacodynamics of the two compounds.