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bioRxiv · 10.1101/2020.06.01.127464

Hemodynamic and electromechanical effects of paraquat in rat heart

Lin, C.-C.·Hsu, K.-H.·Chang, G.-J.
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Abstract

Paraquat (PQ) is a highly lethal herbicide. Ingestion of large quantities of PQ usually results in cardiovascular collapse and eventually death. However, the mechanism of acute PQ poisoning induced cardiotoxicity is poorly understood. Therefore, the purpose of the present study was to aim to investigate the mechanisms of PQ induced cardiotoxicity by examining the effects of PQ on hemodynamics in vivo, as well as in vitro on isolated hearts and ventricular myocytes in rats. Intravenous administration of PQ (100 or 180 mg/kg) in anesthetized rats induced dose-dependent decreases in heart rate, blood pressure, and cardiac contractility (left ventricular [LV] dP/dtmax). Furthermore, it prolonged the rate-corrected QT (QTc) interval. In Langendorff-perfused isolated hearts, PQ (33 or 60 μM) decreased LV pressure and contractility (LV dP/dtmax in isolated ventricular myocytes), PQ (10–60 μM) decreased the amplitude of Ca2+ transients and cell shortening in a concentration-dependent manner. Patch-clamp experiments demonstrated that PQ decreased the amplitude and availability of the transient outward K+ channel (Ito) and altered its gating kinetics. These results suggest that PQ-induced cardiotoxicity results mainly from diminished Ca2+ transients and inhibited K+ channels, which lead to the suppression of LV contractile force and prolongation of the QTc interval.View Full Text

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Lin, C.-C., Hsu, K.-H., Chang, G.-J.. 2020-06-01. Hemodynamic and electromechanical effects of paraquat in rat heart. https://doi.org/10.1101/2020.06.01.127464

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