Piecewise nonlinear mixed-effects models for modeling cardiac function and assessing treatment effects

• Published in: Computer methods and programs in biomedicine Vol. 110; no. 3; pp. 240 - 252
• Main Authors: Jang, Hyejeong, Conklin, Daniel J., Kong, Maiying
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 01.06.2013; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Pressure; Cardiac function; Cardiology. Vascular system; Change point model; Coronary Circulation; Fundamental and applied biological sciences. Psychology; Genes; Glutathione S-Transferase pi - deficiency; Glutathione S-Transferase pi - genetics; Glutathione S-Transferase pi - physiology; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Rate; Injuries; Internal Medicine; Ischemia; Ischemia-reperfusion; Male; Mathematical analysis; Mathematical models; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mixed-effects model; Models, Cardiovascular; Myocardial Reperfusion Injury - enzymology; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - physiopathology; Nonlinear Dynamics; Nonlinearity; Other; Piecewise nonlinear mixed-effects model; Ventricular Function, Left; Vertebrates: cardiovascular system; Piecewise nonlinear mixed-effects model; Ischemia-reperfusion; Mixed-effects model; Change point model; Cardiac function; Heart; Correlation; Injury; Ischemia reperfusion; Change point; Experimental study; Modeling; Left ventricle; Heart rate; Hypothesis test; Mixed model; Non linear model; Repeated measurement; Random effect; Physiology; Cardiology
• ISSN: 0169-2607; 1872-7565; 1872-7565
• DOI: 10.1016/j.cmpb.2012.11.007

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.