Electropharmacological Characterization of Aciclovir in the Halothane-Anesthetized Dogs: A Proposal of Evaluation Method for Cardiovascular Safety Pharmacology of Anti-virus Drugs.

Electropharmacological Characterization of Aciclovir in the Halothane-Anesthetized Dogs: A Proposal of Evaluation Method for Cardiovascular Safety Pharmacology of Anti-virus Drugs. Cardiovasc Toxicol. 2020 Mar 19;: Authors: Kondo Y, Hagiwara-Nagasawa M, Kambayashi R, Goto A, Chiba K, Nunoi Y, Izumi-Nakaseko H, Matsumoto A, Sugiyama A Abstract Given limited information regarding the pathophysiology underlying aciclovir-associated, clinically observed cardiovascular adverse events including chest pain, tachycardia, bradycardia, palpitation, arrhythmia, hypertension and hypotension, we investigated its electropharmacological effects using the halothane-anesthetized beagle dogs. Aciclovir in doses of 2 and 20 mg/kg was sequentially infused over 10 min with an interval of 20 min (n = 4), which would achieve sub-therapeutic to supra-therapeutic levels of plasma concentrations. Aciclovir decreased the total peripheral vascular resistance along with the blood pressure in a dose-related manner, which increased the heart rate, ventricular contraction and atrioventricular nodal conduction speed probably via a reflex-mediated increase of sympathetic tone. No significant change was detected in the intra-atrial or intra-ventricular conduction, indicating that aciclovir may not inhibit atrial or ventricular INa. Aciclovir prolonged the repolarization period in a dose-related as well as in a reverse frequency-dependent manners, indicating tha...
Source: Cardiovascular Toxicology - Category: Cardiology Authors: Tags: Cardiovasc Toxicol Source Type: research