Defense Date

2021

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Dr. Stefano Toldo

Second Advisor

Dr. Antonio Abbate

Third Advisor

Dr. Roland Pittman

Abstract

Heart failure (HF) is characterized by dyspnea, fatigue, and exercise intolerance. Clinical evidence points to increased interleukin-1β (IL-1β) activity in patients with HF, with an IL-1 blockade improving the exercise capacity in HF patients. In healthy mice, recombinant-mouse IL-1β (rmIL-1β) induces acute systolic dysfunction, peaking 4 hours after administration. However, the direct effects of rmIL-1β on exercise capacity are unknown. We hypothesized that rmIL-1β diminishes the exercise capacity in the mouse. Adult mice were trained to run on a treadmill and exercise capacity was assessed before, 4 hours, and 96 hours after intraperitoneal administration of rmIL-1β (3 μg/kg) or vehicle (0.9% NaCl) (N=7-10/group). In separate mice, left ventricular ejection fraction (LVEF) was assessed, at the same time points, after administration of rmIL-1β or vehicle using transthoracic echocardiography. The ultrasound operator was blinded to treatments. The cardiac reserve was measured by calculating the difference in LVEF before and after β-adrenergic stimulation using isoproterenol (10 ng/mouse) (N=5-11/group). Treatment with rmIL-1β significantly reduced exercise capacity after 4 hours and 96 hours (P

Rights

© Habeebah Z. Vohra

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-11-2021

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