Received for publication June 20, 2003.
Revised July 7, 2003.
Accepted for publication August 14, 2003.

Fructose-fed rats are protected against ischemia/reperfusion injury

Abstract

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) (10mg/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 minutes of myocardial ischemia and 4 hours of reperfusion. In rats randomized to placebo, infarct size was significantly reduced by FF (24±5%) as compared to CON (54 ±1%, p<0.05). 5-HD pretreatment 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, while 5-HD administration prior to IPC blunted the IPC effect. In Zucker obese rats infarct size was significantly larger (57±4%) compared to lean controls (37±4%, p<0.05). In FF-3 rats, infarct size was also decreased (20±2%, p<0.01) as compared to 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.

Key words: Zucker obese rat, fructose-fed rat, insulin resistance, ischemia/reperfusion, mitochondrial KATP channel, preconditioning

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