What is the clinical evidence from this study?

Study design: Other. Population: Clearance of cardiac troponin. Intervention: Intravenous injection of labeled cardiac troponin (cTn). Primary outcome: Organ retention and clearance of labeled cTn.

April 22, 2020Open Access

The Liver and Kidneys mediate clearance of cardiac troponin in the rat

Key Result

Intravenously injected labeled cardiac troponin was mainly cleared by the liver (86% of total uptake) and kidneys (12% of total uptake) in rats.

Structured PICO

Population

Male Wistar Kyoto rats and mouse hepatoma cells used to study the clearance mechanisms of cardiac troponin.

Intervention

Intravenous injection of purified pig cardiac troponin (cTn) complex labeled with fluorescent dye (Alexa Fluor 488) or fluorine 18 (18F).

Outcome

Clearance of cTn from plasma and organ accumulation measured by fluorescence signal in organ extracts or 18F signal using positron emission tomography (PET).surrogate

This preclinical study demonstrates that cardiac troponin is primarily cleared from the circulation by the liver and kidneys, providing a mechanistic basis for stable troponin elevations in patients with impaired organ function.

Limitations

Performed in rats without myocardial damage.
Most experiments used cTn prepared from pig heart tissue, which could have species-specific effects in organ targeting.
The dominant form of cTnT and cTnI released from damaged cardiac tissue might differ from the cTn preparations used in this study.

Abstract

Abstract Cardiac-specific troponins (cTn), troponin T (cTnT) and troponin I (cTnI) are diagnostic biomarkers when myocardial infarction is suspected. Despite its clinical importance it is still not known how cTn is cleared once it is released from damaged cardiac cells. The aim of this study was to examine the clearance of cTn in the rat. A cTn preparation from pig heart was labeled with fluorescent dye or fluorine 18 ( 18 F). The accumulation of the fluorescence signal using organ extracts, or the 18 F signal using positron emission tomography (PET) was examined after a tail vein injection. The endocytosis of fluorescently labeled cTn was studied using a mouse hepatoma cell line. Close to 99% of the cTnT and cTnI measured with clinical immunoassays were cleared from the circulation two hours after a tail vein injection. The fluorescence signal from the fluorescently labeled cTn preparation and the radioactivity from the 18F-labeled cTn preparation mainly accumulated in the liver and kidneys. The fluorescently labeled cTn preparation was efficiently endocytosed by mouse hepatoma cells. In conclusion, we find that the liver and the kidneys are responsible for the clearance of cTn from plasma in the rat.

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