High-sensitivity Cardiac Troponin I Changes Following Subcutaneous Needle Puncture, Restraint, and Venipuncture in Cynomolgus Monkeys

Abstract

Background/Aim: Cardiac troponin I (cTnI) is a sensitive biomarker of myocardial injury in which procedure-related stress may cause mild, non-injury-related increases. This study aimed to characterize procedure-related variability of high-sensitivity cTnI and related biomarkers in cynomolgus monkeys and to compare a single molecule counting (SMC) assay with an enzyme-linked immunosorbent assay (ELISA). Materials and Methods: Five male cynomolgus monkeys received subcutaneous physiological saline (2 ml/kg). Blood was collected under restraint at 0 (baseline), 0.5, 1, 2, 4, 8, and 24 h. cTnI was measured by SMC [lower limit of quantification (LLOQ): 0.7 pg/ml] and ELISA (LLOQ: 156 pg/ml). Cardiac troponin T, creatine kinase (CK), lactate dehydrogenase (LDH), and their isoenzymes (CK-MM, CK-MB, LDH1, LDH2, LDH4, LDH5), aspartate aminotransferase (AST), heart-type fatty acid-binding protein (H-FABP), and myoglobin were measured. Post-procedure values were compared with the baseline. Results: With SMC, cTnI was below the LLOQ at baseline in all animals, increased significantly at 2 and 4 h (peak at 4 h: mean approximately 16 pg/ml), and returned to near baseline by 24 h. With ELISA, baseline cTnI was below the LLOQ in four of five animals. Many post-procedure values were also below the LLOQ, although cTnI increased at 2 and 4 h (peak at 4 h). The cTnI quantification rate was higher with SMC (83%) than with ELISA (54%). cTnT, H-FABP, and myoglobin increased transiently and returned to baseline by 24 h, whereas CK and LDH and their isoenzymes and AST increased but remained above baseline at 24 h. Conclusion: Subcutaneous needle puncture, restraint, and venipuncture can produce slight, transient increases in high-sensitivity cTnI. The SMC assay detected low-level variability better than ELISA, supporting stress-aware interpretation with baseline adjustment and control comparisons.