Preoperative dietary restriction reduces intimal hyperplasia and protects from ischemia-reperfusion injury.

ABSTRACT

OBJECTIVE: Whereas chronic overnutrition is a risk factor for surgical complications, long-term dietary restriction (reduced food intake without malnutrition) protects in preclinical models of surgical stress. Building on the emerging concept that acute preoperative dietary perturbations can affect the body's response to surgical stress, we hypothesized that short-term high-fat diet (HFD) feeding before surgery is detrimental, whereas short-term nutrient/energy restriction before surgery can reverse negative outcomes. We tested this hypothesis in two distinct murine models of vascular surgical injury, ischemia-reperfusion (IR) and intimal hyperplasia (IH). METHODS: Short-term overnutrition was achieved by feeding mice a HFD consisting of 60% calories from fat for 2 weeks. Short-term dietary restriction consisted of either 1 week of restricted access to a protein-free diet (protein/energy restriction) or 3 days of water-only fasting immediately before surgery; after surgery, all mice were given ad libitum access to a complete diet. To assess the impact of preoperative nutrition on surgical outcome, mice were challenged in one of two fundamentally distinct surgical injury models IR injury to either kidney or liver, or a carotid focal stenosis model of IH. RESULTS: Three days of fasting or 1 week of preoperative protein/energy restriction attenuated IH development measured 28 days after focal carotid stenosis. One week of preoperative protein/energy restriction also reduced plasma urea, creatinine, and damage to the corticomedullary junction after renal IR and decreased aspartate transaminase, alanine transaminase, and hemorrhagic necrosis after hepatic IR. However, exposure to a HFD for 2 weeks before surgery had no significant impact on kidney or hepatic function after IR or IH after focal carotid stenosis. CONCLUSIONS: Short-term dietary restriction immediately before surgery significantly attenuated the vascular wall hyperplastic response and improved IR outcome. The findings suggest plasticity in the body's response to these vascular surgical injuries that can be manipulated by novel yet practical preoperative dietary interventions.