Cardiac Troponin T Release into Plasma after Acute Myocardial Infarction: Only Fractional Recovery Compared with Enzymes

Abstract

SUMMARY. After acute myocardial infarction (AMI) cardiac enzymes and proteins are released into plasma and are used as biochemical markers of cardiac muscle injury. We studied the completeness of the release of troponin T, a cardiac protein that is largely bound to myofibrillar structures and compared it with the release of cytoplasmic cardiac enzymes in 22 patients with AMI, who were treated with thrombolytic therapy.Creatine kinase (CK; EC 2.7.3.2), hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH; EC 1.1.1.27) and troponin T were assayed serially in plasma samples obtained frequently and for at least 168 h after the start of thrombolytic therapy. Cumulative release of enzymes and troponin T in plasma were calculated by using a two-compartment model for circulating proteins.In order to express the cumulative plasma releases in gram equivalents (g-eq) healthy myocardium per litre plasma (infarct size), we determined HBDH, LDH and total troponin T contents per gram net weight of tissue in 17 human hearts obtained post-mortem from patients who died from non-cardiac causes. Mean (SD) tissue contents per gram wet weight of, respectively, l56±25 Ujg, 385±59 Ujg and 234 ± 65 Ji.gjg were found.For the cardiac enzymes CK, HBDH and LDH the mean (SEM, n = 22) total release over 72 h, was, respectively, 5·9 ± 1'5, 5·9 ± 1·6 and 6·1 ± 1·7 g-eqjL. There was no further increase after 72 h and the differences between enzymes were not significant. The mean (SEM) cumulative troponin T release, expressed in gram equivalents of myocardium per litre of plasma was only O· 30 ± 0·09 g-eqjL after 72 h and O' 51 ± 0·61 g-eq/L after 168 h. After 72 h total recovery of troponin T in g-eqjL was only 5% and after 168 h only 8·5% of the total recovery of cytoplasmic cardiac enzymes after 72 h.Cumulative troponin T release after 72 h and after 168 h correlates well with infarct size, estimated from cumulative cytoplasmic enzyme release. However, quantification of infarct size should preferably be performed from plasma release curves of cytoplasmic cardiac enzymes or proteins in order to prevent underestimation of infarct size, caused by incomplete release of the non-cytoplasmic proteins. Additional key phrases: compartmental model; reperfusion; intracellular compartmentation; quantification of tissue damage

Impaired Renal Clearance Explains Elevated Troponin T Fragments in Hemodialysis Patients

“…So although intact cTnT is too large to be effectively cleared, because of fragmentation, actual clearance rates are normally much higher than previously estimated. 12 These findings are supported by the reports of a rapid decrease of cTnT concentrations in renal transplantation patients. 13,14 The prognostic factor of increased cTnT concentrations in patients with renal failure has been discussed in several articles.…”

“…This results in an estimated negligible loss of 27 mg cardiac tissue per year, based on a renal clearance rate of 1.2 hour Ϫ1 , a plasma volume of 3 L, and a cardiac tissue content of 234 g/g. 12 Clearance of cTnT normally happens with such a speed that serum concentrations are well below the current detection limit of 0.01 g/L. However, impaired renal function leads to a diminished clearance rate that can cause the measurable increase in basal cTnT concentrations.…”

Revision of the Troponin T Release Mechanism from Damaged Human Myocardium

“…1C). As only a small fraction of the available cTnT is extracted from the damaged area per unit of time (6 ), little depletion of available cTnT occurs during the first days, resulting in a steady-state situation in which cTnT delivery to the circulation and clearance is balanced. This steady state will prevail until the available cTnT in the damaged myocardium is depleted to the point at which local plasma flow no longer becomes saturated with cTnT, resulting in a declining delivery of cTnT to the circulation.…”

“…The cTnT/I/C complex takes part in calcium-dependent regulation of the actin-myosin interaction during muscle contraction (3 ). Following an AMI, cTnT is released and can often be measured in patient serum for over a week after the event (4)(5)(6). This is in contrast to other cardiac damage markers such as the creatine kinase muscle-brain fraction (CKMB) and myoglobin (Myo), which are cleared within hours or a few days following myocardial necrosis (6)(7)(8).…”

“…The sustained cTnT increase observed following an AMI is therefore likely due to a delayed release from the damaged myocardium (6 ). It has been assumed on the basis of in vitro extraction studies using buffers in which cTnT has little solubility (14 ) that the delayed release is caused by most of the cTnT being irreversibly bound to its interaction partner tropomyosin and released only following degradation of the myofibrils in necrotic cardiomyocytes (4 ).…”