Introduction: Currently, standardmethods formeasuring cardiac output are either invasive (i.e. flowprobe) or are limited in terms of short measurement intervals and measurement variability (i.e. echocardiography). The ability to reliably measure cardiac output in a non-invasive manner in large animals would provide a valuable tool to expand functional cardiovascular endpoints in preclinical safety studies. PhysioFlow (R) is a novel method that uses waveform analysis of an impedance signal to measure cardiac output non-invasively. Unlike cardiac impedance techniques in the past, PhysioFlow (R) is not dependant on thoracic structure or basal thoracic impedance (Z(0)) and therefore this methodology is transferrable from human to animal models.Methods: Three tool compounds with known effects on cardiac output were administered to conscious beagle dogs to determine if the non-invasive PhysioFlow (R) system could detect the expected changes in stroke volume and cardiac output as determined by literature references using the current standard methodologies (e.g. aortic blood flow and thermodilution).Results: The PhysioFlow (R) system was able to detect increases in cardiac output when dosed with 20 mu g/kg of Dobutamine, a decrease in cardiac output when dosed with 0.1 mg/kg of Acepromazine, and no significant change in cardiac output when dosed with 2 mg/kg of Minoxidil. These results are within expected ranges based on published literature (Stepien et al., 1995; Taylor et al., 2007).Discussion: PhysioFlow (R), a signal morphology-based impedance cardiography, can be utilized to reliably and non-invasively measure cardiac output in beagle dogs. (C) 2016 Elsevier Inc. All rights reserved.

Introduction Assessing the effects of new chemical entities on cardiovascular function is an essential component of nonclinical safety evaluation. Regulatory guidelines advocate the use of telemetry to evaluate drug effects on the cardiovascular system of animal including electrocardiogram (ECG) waveforms. Currently, standard method is to place ECG electrodes subcutaneously and the ECG signals have a suboptimal signal mainly due to movement artifacts. In order to improve and optimize the ECG signal and minimize movement artifacts, a model for continuous monitoring of the ECG in conscious, unrestrained animals by placing ECG electrodes on the pericardium was evaluated.