Development and Characterization of a Novel Small Animal Model of Heart Failure with Preserved Ejection Fraction

Location

Medical Education Building, LSUHSC-NO

Presentation Date

10-10-2019 10:00 AM

End Date

10-10-2019 12:00 PM

Description

Background: Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex heterogeneous syndrome that currently affects approximately 3 million in the US. HFpEF is a significant public health concern since this disease manifests very high morbidity and mortality combined with excessive healthcare expenditures. At present, there are no FDA approved therapies for to treat HFpEF patients. The lack of approved therapies is partially due to the absence of accepted preclinical models that features the multitude of HFpEF co-morbidities and closely mimics the clinical presentation of HFpEF. It is of the utmost importance to establish new animal models that appropriately recapitulate the pathophysiological features of HFpEF. Methods: We investigated 16-week old ZSF-1 rats, (obese and lean controls) with n= 5-6 per group. The obese ZSF-1 rat is genetically predisposed to the development of hypertension, obesity, dyslipidemia, and insulin insensitivity. The rats were studied for a period of 8 weeks. We measured several clinical parameters including cardiac structure and function (2-D echocardiogram), conscious blood pressure (radiotelemeters), exercise capacity (treadmill), and serum lipid and triglyceride levels (standard blood ELISA assays). Results: ZSF-1 obese rats exhibited an increase in the E/A ratio, systemic blood pressure, and cholesterol levels. We also observed impaired responses to glucose administration and decreased exercise capacity. All of these findings are consistent with the HFpEF phenotype observed in human HFpEF patients. This novel model allows for further research into the pathobiology of HFpEF. Conclusion: The establishment of this preclinical model of HFpEF, characterized by a clinically relevant pathological state will provide novel insights into the pathology of HFpEF. Future studies will identify new therapeutic interventions. Ultimately, this animal model will provide a critical therapies. testing platform for novel HFpEF

Comments

Mentor: Dr. David J. Lefer (Director of Cardiovascular Center of Excellence, Louis Levy Professor Department of Pharmacology)

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Oct 10th, 10:00 AM Oct 10th, 12:00 PM

Development and Characterization of a Novel Small Animal Model of Heart Failure with Preserved Ejection Fraction

Medical Education Building, LSUHSC-NO

Background: Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex heterogeneous syndrome that currently affects approximately 3 million in the US. HFpEF is a significant public health concern since this disease manifests very high morbidity and mortality combined with excessive healthcare expenditures. At present, there are no FDA approved therapies for to treat HFpEF patients. The lack of approved therapies is partially due to the absence of accepted preclinical models that features the multitude of HFpEF co-morbidities and closely mimics the clinical presentation of HFpEF. It is of the utmost importance to establish new animal models that appropriately recapitulate the pathophysiological features of HFpEF. Methods: We investigated 16-week old ZSF-1 rats, (obese and lean controls) with n= 5-6 per group. The obese ZSF-1 rat is genetically predisposed to the development of hypertension, obesity, dyslipidemia, and insulin insensitivity. The rats were studied for a period of 8 weeks. We measured several clinical parameters including cardiac structure and function (2-D echocardiogram), conscious blood pressure (radiotelemeters), exercise capacity (treadmill), and serum lipid and triglyceride levels (standard blood ELISA assays). Results: ZSF-1 obese rats exhibited an increase in the E/A ratio, systemic blood pressure, and cholesterol levels. We also observed impaired responses to glucose administration and decreased exercise capacity. All of these findings are consistent with the HFpEF phenotype observed in human HFpEF patients. This novel model allows for further research into the pathobiology of HFpEF. Conclusion: The establishment of this preclinical model of HFpEF, characterized by a clinically relevant pathological state will provide novel insights into the pathology of HFpEF. Future studies will identify new therapeutic interventions. Ultimately, this animal model will provide a critical therapies. testing platform for novel HFpEF