Abstract
Renal ischemia-reperfusion (IR) injury inflicts remote cardiac dysfunction. Studies on rats fed with a high-fat diet (HD) showed contradictory results: some demonstrated increased sensitivity of the heart and kidney to IR injury, while others reported resistance. In this study, we examined cardiac dysfunction and compromised cardiac tolerance associated with renal IR in HD and standard diet (SD) fed rats. Male Wistar rats fed with HD or SD diet for 16 weeks were subjected to either renal sham or IR protocol (bilateral clamping for 45 min and reperfusion for 24 h). The hearts isolated from these rats were further subjected to normal perfusion or IR procedure to study cardiac response. Renal IR surgery negatively affected cardiac function with substantial changes in the cardiac tissues, like mitochondrial dysfunction, elevated oxidative stress, and inflammation. HD-fed rat hearts exhibited hypertrophy at the end of 16 weeks, and the consequential impact on the heart was higher in the animals underwent renal IR surgery than with sham surgery. However, the IR induction in the isolated heart from renal sham or renal IR operation showed significant tissue injury resistance and better physiological recovery in HD-fed rats. However, in SD-fed rats, only hearts from renal IR-operated rats showed resistance to cardiac IR, whereas hearts from renal sham-operated rats were more susceptible to IR damage. The augmented IR resistance in the heart with prior renal surgery was due to preserved mitochondrial bioenergetics function, reduced oxidative stress, and activation of the PI3K/AKT signaling axis.