Serum Chemical Biomarkers of Cardiac Injury for Nonclinical Safety Testing

Abstract

There has been a substantial increase in the number and efficacy of laboratory biomarkers for the evaluation of human cardiac injury over the last decade. The advantages of these over traditional laboratory tests have encouraged adoption of comparable markers in nonclinical studies for cardiac injury assessment. Of particular interest are markers that are not only more sensitive and/or specific than traditional parameters for cardiac injury, but also those that may directly bridge human and laboratory animal safety testing. However, a majority of recently developed markers are quantified through antibody-based assays, and cross-reactivity with the comparable analyte in nonhuman samples is difficult to predict and often species-variable. The utility of these novel biomarkers thus, depends upon adequate assay validation with each laboratory species of interest. In contrast, traditional laboratory parameters of cardiac injury lack the properties of an ideal biomarker, but are well established and have an extensive database in nonclinical safety assessment. The current status and utility of both recently developed and traditional biomarkers of cardiac injury in nonclinical testing, and considerations for validation of novel biomarkers of cardiac injury are reviewed.

Effect of Conjugated Linoleic Acid Intake on Endurance Exercise Performance and Anti-fatigue in Student Athletes

“…There was also no significant difference in the LD 1 /LD 2 ratio between the two groups in this study. For most, LD 5 predominates in skeletal muscle and the liver 47 , and it increased in serum in patients with non-traumatic acute rhabdomyolysis 49 . In this study, there was no significant difference in LD 5 between the two groups, and there was no indication that CLA intake inhibited leaking of LD 5 from skeletal muscle cells.…”

“…LD 1 and LD 2 are cardiacpredominant isozymes. Increase of these isozymes in serum is considered generally supportive of myocardial injury 47 . Huang et al 48 reported that endurance training accelerates exhaustive exercise-induced apoptosis in left ventricles of rats, as a result of exhaustive running tests on a treadmill.…”

Comparison of the specificity of cardiac troponin I and creatine kinase MB in isoproterenol-induced cardiotoxicity model in rats

“…Apple 1999) and preclinical research (e.g. Walker 2006). In our study, the myocardial specificity of cTnI was proven by the significant differences in the concentrations of cTnI between ISO animals and control animals at several time intervals (2, 4, 6, and 24 h).…”

Refinement of tourniquet-induced peripheral ischemia/reperfusion injury in rats: comparison of 2 h vs 24 h reperfusion

“…However, after 24 h of reperfusion only very low levels of CK-MM were measured, as CK-MM is a marker of early detection of muscle injury and has a serum half-life of only about one hour in rats. 23 Additionally, we looked at the plasma level of PDGF-bb, which is known to have angiogenic effects, regulates the tonus of blood vessels and is involved in wound healing. 24,25 At low levels PDGF-bb is expressed in the endothelium, platelets and macrophages, which increases following mechanical injury and atherosclerosis.…”