Differential analysis of transient increases of serum cTnI in response to handling in rats.

Serum cardiac troponins are the key biomarkers of myocardial necrosis in humans and in preclinical species. The use of ultrasensitive assays for serum cardiac troponin I (cTnI) as a biomarker in safety studies is hampered by interindividual differences. In this study, we investigated the effect of handling procedures on serum cTnI and explored modeling and simulation approaches to mitigate the impact of these interindividual differences.

Myocardial mononuclear cell infiltrates are not associated with increased serum cardiac troponin I in cynomolgus monkeys.

Myocardial mononuclear cell infiltrate is a spontaneous cardiac finding commonly identified in laboratory cynomolgus monkeys. The infiltrates are predominantly composed of macrophages with lesser lymphocytes and are not typically associated with histologically detectable cardiomyocyte degeneration. These infiltrates are of concern because they confound interpretation of test article-related histopathology findings in nonclinical safety toxicology studies.

The complete pharmacokinetic profile of serum cardiac troponin I in the rat and the dog.

Recent improvements in assays have allowed serum cardiac troponin I (cTnI) to be measured at previously undetectable concentrations, which may have implications for cardiotoxicity studies. We characterized the pharmacokinetics of cTnI after a single iv administration of purified cTnI in rats at doses of 0.005, 0.

Serum cardiac troponin I concentrations transiently increase in rats given rosiglitazone.

Rosiglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist of the thiazolidinedione class, is a major insulin-sensitizing drug widely used to treat type-2 diabetes. Rosiglitazone causes myocardial hypertrophy in rodents and increases the risk of cardiac events in man. To better characterize its cardiac effects, male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone.

Time course characterization of serum cardiac troponins, heart fatty acid-binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat.

We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 microg/kg).