Fetal cardiac troponin I levels decline toward birth in sheep

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 326; no. 6; pp. H1538 - H1543
• Main Authors: Jonker, Sonnet S, Louey, Samantha
• Format: Journal Article
• Language: English
• Published: United States 01.06.2024
• Subjects: Animals; Animals, Newborn; Biomarkers - blood; Female; Fetal Blood - metabolism; Fetus - metabolism; Insulin-Like Growth Factor I - metabolism; Parturition; Pregnancy; Sheep; Troponin I - blood; proliferation; biomarker; cardiac injury; heart; normal development
• ISSN: 0363-6135; 1522-1539; 1522-1539
• DOI: 10.1152/ajpheart.00224.2024

Elevated cardiac troponin I (cTnI), a myocardial damage biomarker, has been reported in cord blood of neonates delivered vaginally or by cesarean section. Although the neonatal peak likely reflects the physiological adjustment to extrauterine life, a better understanding of serial prepartum changes is required to determine physiological causes of fetal cTnI release. We longitudinally sampled eight healthy lambs (20 days before spontaneous birth to 5 days postnatal), and from three fetuses receiving intravenous IGF-1. Samples were collected into heparin, and the plasma was stored at -80°C for later determination of high-sensitivity (hs) cTnI levels (BeckmanCoulter UniCel DxI Access IA; log transformed detection limit = 0.30, quantification limit = 0.78, 99th percentile = 1.78). Positive and negative control samples were drawn from an adult ewe during a terminal experiment (myocardial ischemia) and similarly assessed. hs-cTnI data were log transformed from ng/L. Log(hs-cTnI) was 1.47 ± 0.30 (means ± SD) at 20 days before birth and declined to 1.02 ± 0.65 in fetuses 12 ± 4 h before birth ( < 0.0001, = 0.7869). Birth stimulated a delayed, transient peak in hs-cTnI ( = 0.0058). Newborn (43 ± 19 min postnatal) levels were 1.39 ± 0.40 ( = 0.0650 vs. fetus on day of birth) and 2.14 ± 0.63 the day after birth ( = 0.0331 vs. newborn). The second day after birth, levels declined to 1.65 ± 0.48 ( = 0.0238 vs. ). IGF-1 infusion increased hs-cTnI levels 25-50% over baseline ( = 0.0252, = 0.9938). Baseline adult ewe log(hs-cTnI) was below the limit of detection; 3 h following coronary artery ligation, levels were 3.21. In conclusion, we newly report that fetal hs-cTnI levels decline concomitantly with reduced proliferation of cardiomyocytes toward term. Serial blood samples were collected from catheterized, normally developing fetal and newborn lambs and high-sensitivity cardiac troponin I (hs-cTnI) levels were assessed, providing unprecedented insight into the physiological processes leading to high levels in the perinatal period. Moderately high levels of hs-cTnI found in the normally developing fetus declined toward term. An elevation to high levels peaked the day after birth, after which hs-cTnI declined again. Stimulation of fetal cardiomyocyte proliferation with IGF-1 also elevated hs-cTnI.