Introduction: Anesthetised guinea pig represents a model for evaluation of arrhythmogenic potential of drugs. It allows to evaluate complex reaction of cardiovascular system. Moreover, cardiac action potential of guinea pig is quite comparable to that of human and the results are thus well translatable to clinical medicine. Aim of this study was to evaluate arrhythmogenic potential of the TP-1, a new drug candidate with possible beta adrenergic action, in the model of anesthetised guinea pig.
Methods: 24 guinea pigs were divided into three groups: positive control (esmolol, cardioselective beta-1 receptor blocker), negative control (vehiculum) and test group (TP-1). Animals were anesthetised by isoflurane, fixed to the heated pad, their neck and chest shaved, and jugular vein cannulated. ECG was recorded by needle electrodes subcutaneously fixed on the chest. Animal was stabilized. Then 4 doses of a drug or vehiculum were administered by rapid i.v. infusion. ECG and body temperature was recorded continually during the whole experiment using PowerLab (AD Instruments Ltd., CO, USA). ECG record was analysed using LabChart 8 Pro (AD Instruments Ltd., CO, USA). RR intervals and QT intervals were measured. QT was corrected according to Bazzet’s and Fridericia’s formulas. Incidence of arrhythmias was evaluated. Statistical analyses were performed in GraphPad Prism 5 (GraphPad Software, CA, USA). The results were compared between the groups and between particular doses within each group.
Results: Dose-dependent changes of RR interval as well as QTc interval were observed in all groups. As expected according to in silico analyses, rapid onset of TP-1 effect and its short-term action on guinea pig ECG were observed in test group. Detailed results will be included in fulltext.
Conclusion: Since effects of TP-1 has not been tested up to now, further experiments are needed to obtain deeper insights into its action on cardiac electrical activity.