Circulating Fetal Troponin I May Reflect Cardiomyocyte Proliferation

Abstract

INTRODUCTION: Circulating biomarkers such as Troponin I (TnI) that are typically indicative of myocardial damage in adults have been reported to be detectable in cord blood of healthy infants delivered both vaginally and by cesarean section prior to labor. We performed serial sampling of healthy fetal sheep from ~20 days before spontaneous birth to 5 days postnatal in order to describe normal developmental values of circulating TnI. METHODS: Seven fetal sheep were surgically instrumented with indwelling catheters advanced into the ascending aorta and the superior vena cava. Following surgical recovery, daily blood samples were taken first thing in the morning into heparin, and the plasma was frozen for later determination of high-sensitivity (hs) TnI levels (BeckmanCoulter UniCel DxI Access IA; log transformed limit of detection =0.30, limit of quantification =0.78, and 99th%ile =1.78). Positive and negative control samples were drawn from an adult ewe during a terminal experimental ligation of the left anterior descending coronary artery and similarly assessed. hs-TnI data were log transformed from ng/L, visually assessed, and outliers removed by the ROUT method. RESULTS: Log(hs-TnI) was 1.47±0.30 at 20 days before birth and declined to 0.88±0.36 in fetuses 12±4 hour before birth (p<0.0001, R2=0.8444). Birth stimulated a delayed, transient peak in hs-TnI (P=0.0058). In the newborn, 43±19 min after birth, levels were 1.39±0.40 (P=0.0650 vs. fetus on day of birth). The day after birth, log(hs-TnI) increased to 2.14±0.63 (P=0.0331 vs. newborn). The second day after birth, levels declined to 1.65±0.48 (P=0.0238 vs. day 1). Adult ewe log(hs-TnI) was below the limit of detection; three hours following coronary artery ligation, levels were 3.21. CONCLUSIONS: This study confirms that hs-TnI levels are moderate to high in healthy sheep fetuses, and reports for the first time that they decline towards term. Why TnI is elevated in the healthy fetus is unknown. If cardiomyocyte TnI is leaked during cytokinesis, the decline towards birth may reflect the diminishing rate of proliferation in this same period. The postnatal hs-TnI peak, above the clinical threshold for evidence of myocardial ischemia in adult humans, may result from hemodynamic, oxidative, or metabolic stresses associated with the establishment of postnatal physiology. This work was funded by an award from the NHLBI (R01HL142483). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.