Human and canine cardiac troponin T and creatine kinase-MB distribution in normal and diseased myocardium. Infarct sizing using serum profiles.

Objective: Cardiac troponin T (cTnT) has been suggested as a new, more specific marker of myocardial cellular damage. The objectives of this study were to examine the distribution of cTnT and creatine kinase (CK)-MB in normal and diseased heart tissue of dogs and humans, and to assess the use of serum cTnT for the estimation of infarct size in dogs.
Design: Serial serum specimens over 7 days were obtained from normal dogs (controls, n = 3) and dogs that underwent surgical coronary artery occlusion (n = 6). Heart muscle samples were obtained from the controls and after 3 weeks of occlusion in experimental dogs. Diseased human heart muscle samples were obtained at autopsy from patients who had died of acute myocardial infarction (n = 3). Normal heart muscle samples (n = 3) were obtained at autopsy from patients who died of non-cardiac-related illnesses. Tissues were sectioned and homogenized to harvest both cytosolic and myofibril-bound proteins. Serum samples and tissue homogenates were assayed for cTnT, CK-MB, and myoglobin (humans only). Total protein was assayed on homogenate samples and results were reported as milligrams per gram of total protein.
Results: The distributions of cTnT, CK-MB, and myoglobin were equivalent across 14 sites within normal human heart. Creatine kinase-MB and myoglobin were more than 99% cytosolic. Cardiac troponin T was 92% myofibril bound and 8% cytosolic. In the control dog hearts, cTnT was higher and CK-MB was lower in the right ventricle than in the left ventricle. While CK-MB and myoglobin were more than 99% cytosolic, cTnT was 98% myofibril bound and 2% cytosolic. Infarct sizing in dog hearts initially did not correlate well with serum cTnT or CK-MB concentrations. However, when the data were separated by infarct location (right coronary artery; left circumflex coronary artery), the correlations improved dramatically. Differences in tissue concentrations of cTnT and CK-MB between the left and right ventricle might explain the change in correlations. Coronary artery occlusion in dogs and humans resulted in decreased cytosolic and myofibril cTnT and increased CK-MB and myoglobin in diseased myocardial tissue.
Conclusions: Our observed biochemical alterations suggest that the energy-producing proteins CK-MB and myoglobin are upregulated following cellular damage, while the structural and regulatory protein cTnT does not have a mechanism for replacement of lost protein following cell injury and necrosis.