PT - JOURNAL ARTICLE AU - James E. Jordan AU - Steven A. Simandle AU - Christina D. Tulbert AU - David W. Busija AU - Allison W. Miller TI - Fructose-Fed Rats Are Protected against Ischemia/Reperfusion Injury AID - 10.1124/jpet.103.055970 DP - 2003 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1007--1011 VI - 307 IP - 3 4099 - http://jpet.aspetjournals.org/content/307/3/1007.short 4100 - http://jpet.aspetjournals.org/content/307/3/1007.full SO - J Pharmacol Exp Ther2003 Dec 01; 307 AB - This study examines the relationship between insulin resistance (IR) induced by fructose feeding (FF) and susceptibility to myocardial ischemia/reperfusion injury (MI/R). Six-week-old male Sprague-Dawley rats were randomized into control (CON; n = 59) or FF (n = 58) groups. After 4 weeks, rats were further randomized into one of the following groups: placebo, ischemic preconditioning (IPC), 5-hydroxydecanoic acid (5-HD) (10 mg/kg), or 5-HD + IPC. Moreover, to determine the role of fructose, a second model of IR (Zucker obese) and rats fed fructose diet for 3 days (FF-3) were also subjected to MI/R. In all experiments, rats were subjected to 30 min of myocardial ischemia and 4 h of reperfusion. In rats randomized to placebo, infarct size was significantly reduced by FF (24 ± 5%) compared with CON (54 ± 1%, p < 0.05). Pretreatment with 5-HD did not alter the infarct size in CON (45 ± 5%) but inhibited the protection afforded by FF (53 ± 7%). IPC reduced the infarct size to an equivalent level in both groups, whereas 5-HD administration prior to IPC blunted the IPC effect. In Zucker obese rats, infarct size was significantly larger (57 ± 4%) compared with lean controls (37 ± 4%, p < 0.05). In FF-3 rats, infarct size was also decreased (20 ± 2%, p < 0.01) compared with CON. This study suggests that fructose feeding affords protection against MI/R that is related to or mimics preconditioning. This protection is not consistent with other models of IR and is likely related to the fructose diet itself. The American Society for Pharmacology and Experimental Therapeutics