Guinea Pig ECG Changes under the Effect of New Drug Candidate TP28b

Abstract

Anesthetized guinea pig represents a valuable model for evaluation of arrhythmogenic potential of various drugs. Aim of this study was to evaluate arrhythmogenic potential of the TP28b, a new drug candidate with possible beta-adrenergic action. Guinea pigs were anesthetized by isoflurane and jugular vein was cannulated. ECG was recorded by needle electrodes fixed subcutaneously on the chest. Rectal probe was used for continual monitoring of body temperature. Animals were divided into positive control, negative control and test group. The experiment consisted of stabilization, 3 phases of tested drug or vehiculum administration by continual i. v. infusion and recovery. The ECG was recorded and analysed using LabChart 8 Pro software. The heart rate, PR intervals, QRS duration, and QT intervals were measured. QT was corrected according to Framingham study. Our experimental model proved to be stable during the whole experiment since the HR, PR interval, QRS interval, and QTc do not change in negative control in all phases. Esmolol administration led to HR decrease, PQ interval and QRS duration prolongation, whereas only small variations of QTc were detected. Our model proved to be valuable and suitable for testing of newly synthetized drugs with cardiovascular effects.