TY - JOUR T1 - Fructose-Fed Rats Are Protected against Ischemia/Reperfusion Injury JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1007 LP - 1011 DO - 10.1124/jpet.103.055970 VL - 307 IS - 3 AU - James E. Jordan AU - Steven A. Simandle AU - Christina D. Tulbert AU - David W. Busija AU - Allison W. Miller Y1 - 2003/12/01 UR - http://jpet.aspetjournals.org/content/307/3/1007.abstract N2 - 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 ER -