Fructose-fed rats are protected against ischemia/reperfusion injury

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.