A highly effective antineoplastic agent, Doxorubicin (DOX), is associated with dose-dependent cardiotoxicity. Some evidence indicates that exercise preconditioning can have cardioprotective effects against DOX-induced cardiac dysfunction. PURPOSE: The purpose of this investigation was to evaluate the effects of exercise preconditioning on DOX-induced cardiac dysfunction using discriminant analysis. With this statistical procedure, we used data from previously completed studies to determine group classification and determine which cardiac function variable is the best predictor of cardiac function. METHOD: Male Sprague-Dawley rats (10 week) were randomly assigned to one of three primary groups: sedentary (SED), wheel running (WR) or treadmill (TM). Following 10 weeks of exercise preconditioning, exercise groups received a bolus i.p. injection of 10 mg/kg of DOX (TM+DOX, WR+DOX). At the same time, the SED group received a bolus injection of either 10 mg/kg of DOX (SED+DOX) or an equivalent volume of saline (SED+SAL). Left ventricle function was assessed ex vivo using an isolated working heart model at 5 days, 10 days, or 28 days post injection. A multiple analysis of variance (MANOVA) was used to determine if a significant difference existed between the five cardiac function variables (ESP, DDP, LVDP, dP/dtmax, and dP/dtmin). Stepwise discriminant analysis was performed to determine which cardiac function variable was the best predictor of cardiac function. Descriptive discriminant analysis was used as a linear classification tool to categorize control and experimental groups. RESULTS: A significant difference existed across the 5 cardiac function variables F(12,344.24)=8.73, P＜0.001. Stepwise discriminant analysis revealed LVDP was the most indicative cardiac function variable remaining in the model (R2 =0.39, F=30.34, P＜0.0001). Five days post DOX treatment, 92% of TM+DOX and 70% of WR+DOX were categorized as SED+SAL. Ten days post DOX exposure, 91% of TM+DOX and 86% of WR+DOX were categorized as SED+SAL. Furthermore, 88% of TM+DOX and 93% of WR+DOX 28 days post DOX treatment were categorized as SED+SAL. CONCLUSION: LVDP appears to be the most indicative ex vivo parameter of cardiac function. The cardiac function of the majority of aerobically trained rats treated with DOX was categorized as SED+SAL up to 28 days post DOX treatment.
- Doxorubicin (DOX)