Evaluation of immunomodulatory biomarkers in a pressure overload model of heart failure

Study Objectives. To characterize the immunomodulatory response in a pressure overload model of heart failure, and to further validate this animal model of human heart failure. Design. Randomized, controlled, animal study. Setting. Large university research facility. Animals. Twenty-seven, male, Sprague-Dawley rats. Intervention. The rats underwent either aortic constriction or a sham procedure. Measurements and Main Results. Six months after the surgical procedure, echocardiographic measurements were obtained, the animals were sacrificed, and plasma samples were taken to measure concentrations of biomarkers. As six (40%) of the 15 rats in the aortic-constriction group died before the 6 months, only nine rats from this group underwent immunomodulatory evaluation. Compared with the sham procedure, aortic constriction increased the left ventricle:body weight ratio in the rats (p=0.0016) It also decreased the velocity of circumferential shortening (p=0.08) and increased myocardial expression of atrial natriuretic factor, beta-myosin heavy chain, and fibronectin (p < 0.05). Concentrations of the proinflammatory mediator interleukin (IL)-1 beta and the counterregulatory mediator IL-10 also significantly increased (p < 0.04) in the group that underwent aortic constriction compared with the group that underwent the sham procedure. Nonsignificant increases (mean change similar to 50-180%) were also observed for IL-2, IL-6, and leptin concentrations. Conclusions. In this classic animal model of heart failure, a systemic immunomodulatory response was evaluated after 6 months of pressure overload resulting in myocardial decompensation and, in some cases, mortality The findings are similar to the immunomodulatory response that may be observed in human heart failure. These novel results further define this model of heart failure and suggest another aspect of its relevance to human heart failure with regard to pressure overload and the immunomodulatory response.