Advisor

Hayward, Reid

Committee Member

Hydock, David S. (David Scott)

Committee Member

Schneider, Carole M.

Department

Sport and Exercise Science

Institution

University of Northern Colorado

Type of Resources

Text

Place of Publication

Greeley (Colo.)

Publisher

University of Northern Colorado

Date Created

8-1-2013

Genre

Thesis

Extent

90 pages

Digital Origin

Born digital

Description

Diabetes is a metabolic disorder that affects over 25 million Americans. Large epidemiological studies have shown that individuals with diabetes are at increased risk of many types of cancer, including those often treated with the cardiotoxic anticancer drug doxorubicin (DOX). The combination of diabetes and DOX can cause severe cardiac dysfunction, possibly from the adverse effects on cardiac metabolism. Diabetes leads to a shift away from glucose metabolism, while DOX shifts to predominately anaerobic glycolysis. The combination could lead to extremely low levels of ATP. Exercise has the potential to attenuate these adverse metabolic effects by increasing ATP synthesis. The purpose of this study was to examine the effect of endurance exercise on the combined effects of streptozotocin (STZ) -induced diabetes and DOX on cardiac function. METHODS: Six week old male Sprague Dawley rats were assigned to either STZ or placebo injection. After confirmed diabetes, animals were assigned to either treadmill training (TM) or sedentary (SED) groups. Following the 8 week activity period, animals were treated with either 12.5 mg/kg DOX or saline (SAL) injection. Cardiac function was measured five days post DOX/SAL injections, using both in vivo and ex vivo assessments. High performance liquid chromatography (HPLC) was used to quantify the amount of phosphometabolites (ATP, ADP, AMP, creatine, and phosphocreatine) in the left ventricular tissue to access metabolic dysfunction. RESULTS: The STZ groups had significant declines in fractional shortening (FS) and relative wall thickness (RWT), -9% and -31%, respectively, compared to non-diabetic groups (p < .05). Left ventricular developed pressure (LVDP) was significantly increased with STZ treatment (16%) and decreased with DOX treatment (-18%). Exercise improved LVDP compared to sedentary animals, although not significantly. Exercise training increased ATP content in STZ treated animals by 27% and 20% in those treated with DOX, p < .05. In addition, exercise training increased Cr levels in STZ and DOX treated groups by 62% and 47%, respectively, p<.05. CONCLUSIONS: Exercise training provides a protective effect against STZ and DOX-induced cardiac dysfunction. In addition, exercise training significantly increased the availability of phosphometabolites in the left ventricle.

Degree type

PhD

Degree Name

Doctoral

Language

English

Local Identifiers

Greufe_unco_0161D_10296

Rights Statement

Copyright is held by author.

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