Abstract
SummaryObjectiveThe aim of this experimental study was to investigate whether hypertonic saline or sodium bicarbonate administration prevented the development of cardiotoxicity in rats that received toxic doses of amitriptyline.MethodThirty-six Sprague Dawley rats were used in the study. The animals were divided into six groups. Group 1 received toxic doses of i.p. amitriptyline. Groups 2 and 3 toxic doses of i.p. amitriptyline, plus i.v. sodium bicarbonate and i.v. hypertonic saline, respectively. Group 4 received only i.v. sodium bicarbonate, group 5 received only i.v. hypertonic saline, and group 6 was the control. Electrocardiography was recorded in all rats for a maximum of 60 minutes. Blood samples were obtained to measure the serum levels of sodium and ionised calcium.ResultsThe survival time was shorter in group 1. In this group, the animals’ heart rates also decreased over time, and their QRS and QTc intervals were significantly prolonged. Groups 2 and 3 showed less severe changes in their ECGs and the rats survived for a longer period. The effects of sodium bicarbonate or hypertonic saline treatments on reducing the development of cardiotoxicity were similar. The serum sodium levels decreased in all the amitriptyline-applied groups. Reduction of serum sodium level was most pronounced in group 1.ConclusionEmpirical treatment with sodium bicarbonate or hypertonic saline can reduce the development of cardiotoxicity during amitriptyline intoxication. As hypertonic saline has no adverse effects on drug elimination, it should be considered as an alternative to sodium bicarbonate therapy.
Highlights
Empirical treatment with sodium bicarbonate or hypertonic saline can reduce the development of cardiotoxicity during amitriptyline intoxication
As hypertonic saline has no adverse effects on drug elimination, it should be considered as an alternative to sodium bicarbonate therapy
Blockage of the rapid sodium channels is responsible for drug-induced cardiotoxicity, which clinically manifests as PR, QT and QRS prolongation, ventricular or supraventricular arrhythmias, hypotension and heart failure.[1,3]
Summary
The experiments were performed on adult female Sprague Dawley rats weighing 250 to 300 g that were obtained from the Ondokuz Mayis University vivarium. The rats were kept in a vivarium maintained at 22 ± 1°C with a 12-hour alternating light–dark cycle. All the experiments were approved by the Institutional Animal Care and Use Committee of Ondokuz Mayis University, and adhered to the guidelines of the Committee on Human/ Animal Experimentation (institutional or regional), and the Helsinki Declaration of 1975, as amended in 1983. Amitriptyline was obtained from Sigma-Aldrich Chemical Co (St Louis, Missouri, USA). It was dissolved in distilled water at a concentration of 50 mg/4 ml. HS solution (3% sodium chloride, sodium 512 mEq/l) and NaHCO3 8.4% (sodium 1 mEq/ml) were used
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