Abstract
Paraquat (PQ) is a highly lethal herbicide. Ingestion of large quantities of PQ usually results in cardiovascular collapse and eventual mortality. Recent pieces of evidence indicate possible involvement of oxidative stress- and inflammation-related factors in PQ-induced cardiac toxicity. However, little information exists on the relationship between hemodynamic and cardiac electromechanical effects involved in acute PQ poisoning. The present study investigated the effects of acute PQ exposure on hemodynamics and electrocardiogram (ECG) in vivo, left ventricular (LV) pressure in isolated hearts, as well as contractile and intracellular Ca2+ properties and ionic currents in ventricular myocytes in a rat model. In anesthetized rats, intravenous PQ administration (100 or 180 mg/kg) induced dose-dependent decreases in heart rate, blood pressure, and cardiac contractility (LV +dP/dtmax). Furthermore, PQ administration prolonged the PR, QRS, QT, and rate-corrected QT (QTc) intervals. In Langendorff-perfused isolated hearts, PQ (33 or 60 μM) decreased LV pressure and contractility (LV +dP/dtmax). PQ (10-60 μM) reduced the amplitudes of Ca2+ transients and fractional cell shortening in a concentration-dependent manner in isolated ventricular myocytes. Moreover, whole-cell patch-clamp experiments demonstrated that PQ decreased the current 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 in cardiomyocytes, which lead to LV contractile force suppression and QTc interval prolongation. These findings should provide novel cues to understand PQ-induced cardiac suppression and electrical disturbances and may aid in the development of new treatment modalities.
Highlights
Paraquat (PQ) is a highly toxic herbicide that causes significant mortality when ingested
The major findings of this study are as follows: (1) PQ decreased heart rate, arterial blood pressure, and cardiac contractility, as well as prolonged the PR, QRS, QT, and QTc intervals in a dose-dependent manner in anesthetized rats; (2) PQ decreased left ventricular (LV) developed pressure and contractility in the Langendorff-perfused rat hearts; (3) PQ decreased both the amplitude of Ca2+ transients and fractional cell shortening in a concentration-dependent manner in rat ventricular myocytes; and (4) PQ suppressed Ito and Iss channels and reduced the availability and altered the gating kinetics of Ito channels
This study demonstrated that acute paraquat exposure produces negative hemodynamic and electromechanical effects in rat hearts
Summary
Paraquat (PQ) is a highly toxic herbicide that causes significant mortality when ingested. It is a widely used herbicide because of its excellent ability to eliminate weeds [1]. Intentionally ingesting PQ to commit suicide is a common problem in some Asian countries 381571-3) to C.C. Lin. The funders had no role in study design, data collection, analysis, decision to publish, or manuscript preparation
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