Effects of repeated restraint and blood sampling with needle injection on blood cardiac troponins in rats, dogs, and cynomolgus monkeys

While cardiac troponins (cTnT and cTnI) have been used as blood biomarkers of myocardial injury such as myocardial infarction in both humans and animals, their high diagnostic sensitivity inevitably leads to decreased diagnostic specificity. For example, it is difficult to judge whether a slight increase of cardiac troponins in toxicological studies is a treatment-related response or not. Drawing an accurate conclusion requires reliable background data and definitive criteria based on that data. However, no organized efforts in setting such criteria has been reported. Here, we measured blood cTnI and cTnT concentrations in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys from repeated blood samplings using needle cylinders under restraint up until 24 h after a single oral dose of 0.5 w/v% methyl cellulose solution as a vehicle. We revealed the extent of individual differences in baseline levels and operational effects. Our results can be useful in making criteria for judgment of treatment-related changes in cardiac troponins.