title: Piecewise nonlinear mixed-effects models for modeling cardiac function and assessing treatment effects.
abstract: Mixed-effects model is an efficient tool for analyzing longitudinal data. The random effects in a mixed-effects model can be used to capture the correlations among repeated measurements within a subject. Mixed effects model can be used to describe individual response profile as well as population response profile. In this manuscript, we apply mixed-effects models to the repeated measurements of cardiac function variables including heart rate, coronary flow, and left ventricle developed pressure (LVDP) in the isolated, Langendorff-perfused hearts of glutathione s-transferase P1/P2 (GSTP) gene knockout and wild-type mice. Cardiac function was measured before and during ischemia/reperfusion injury in these hearts. To describe the dynamics of each cardiac function variable during the entire experiment, we developed piecewise nonlinear mixed-effects models and a change point nonlinear mixed effect model. These models can be used to examine how cardiac function variables were altered by ischemia/reperfusion-induced injury and to compare the cardiac function variable between genetically engineered (null or transgenic) mice and wild-type mice. Hypothesis tests were constructed to evaluate the impact of deletion of GSTP gene for different cardiac function variables. These findings provide a new application for mixed-effects models in physiological and pharmacological studies of the isolated Langendorff-perfused heart.
authors.affiliation: Department of Bioinformatics and Biostatistics, SPHIS, University of Louisville, Louisville, KY, USA.
authors.forename: Hyejeong
authors.initials: H
authors.lastname: Jang
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Conklin
authors.forename: Maiying
authors.initials: M
authors.lastname: Kong
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation; D051549:Glutathione S-Transferase pi / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006339:Heart Rate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D017711:Nonlinear Dynamics; D016277:Ventricular Function, Left
chemical_list: D051549:Glutathione S-Transferase pi; C496557:Gstp1 protein, mouse