Hemodynamic and electromechanical effects of paraquat in rat heart

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.

Rat Electrocardiography and General Anesthesia

“…A moderate prolongation was also found under chloralose anesthesia [77] and similar prolongations under ether anesthesia [99-101, 103, 104]. The shorter QT interval duration was under urethane [45,52,55,56,60,135,137,138] and tribromoethanol [106] anesthesia compared with telemetry studies. Isoflurane [72, 74,75,120,121] and desflurane anesthesia [72] did not affect QT interval duration.…”

“…If we consider that the average HR value with the range reported in telemetry studies involving male rats is our desired reference value, then a slightly increased average HR in pentobarbital (approximately 28 beats/min.) [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], and urethane anesthesia (approximately 32 beats/min) [52][53][54][55][56][57][58][59][60]. In female rats under pentobarbital anesthesia, baseline HR values were reported in only one study, depending on the LD Table 1.…”

“…Duration of the PR (PQ ) interval from telemetry studies [21, 23-25, 30, 117-119], inhalation (isoflurane) [72, 74,75,120,121] pentobarbital [32, 34, 36, 37, 40, 43-47, 49, 122-126], thiopental [63-65, 68, 71], urethane [45,52,53,56,60,128], and ether anesthesia [99][100][101]104] did not differ significantly from one another. The shortened duration of the PR (PQ ) interval was under ketamine/xylazine anesthesia [45,78,79,84,85,89,91,92,[127][128][129].…”

“…When comparing the duration of the QTc interval with the mean value from telemetry studies [26,30,31,117,118], significant prolongation occurred under pentobarbital [32, 38, 41-43, 47, 51] ketamine/xylazine [87, 90-92, 129, 136, 152, 153], and urethane [52,57,60] anesthesia, with moderate prolongation under thiopental [31,62,63,66,68,71] anesthesia. The shortened QTc interval duration compared with the mean value from telemetry studies was under isoflurane anesthesia [72, 74,75,121].…”

Unraveling the link between severe bradycardia and paraquat poisoning

“…Paraquat-induced pulmonary fibrosis has been abundantly reported in the literature, with evidence of its mechanism, clinical manifestation, and treatment strategies [6]. However, little to no evidence exists on the hemodynamic and cardiac electromechanical effects of acute paraquat poisoning [7]. Cases of extreme bradycardia following paraquat poisoning are particularly rare [8].…”