Kaspar Trocha1, Peter Kip1, Michael R MacArthur2, Sarah J Mitchell2, Alban Longchamp3, Jose Humberto Treviño-Villarreal2, Ming Tao3, Miriam A Bredella4, Karen De Amorim Bernstein5, James R Mitchell2, Charles Keith Ozaki6. 1. Division of Vascular and Endovascular Surgery, Brigham & Women's Hospital, Boston, MA; Harvard T.H. Chan School of Public Health, Department of Genetics and Complex Diseases, Boston, Massachusetts. 2. Harvard T.H. Chan School of Public Health, Department of Genetics and Complex Diseases, Boston, Massachusetts. 3. Division of Vascular and Endovascular Surgery, Brigham & Women's Hospital, Boston, MA. 4. Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. 5. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. 6. Division of Vascular and Endovascular Surgery, Brigham & Women's Hospital, Boston, MA. Electronic address: CKOzaki@partners.org.
Abstract
BACKGROUND: Dietary restriction (DR), defined as reduced nutrient intake without malnutrition, is associated with longevity extension, improved glucose metabolism, and increased stress resistance, but also poor wound healing. Short-term preoperative DR followed by a return to normal feeding after surgery results in improved surgical outcomes in preclinical models. However, the effect of preoperative DR on wound healing and perioperative glucose homeostasis is currently unknown. Here, we tested the effects of two different preoperative DR regimens-protein restriction (PR) and methionine restriction (MR)-on wound healing and perioperative glucose homeostasis using an established murine model of wound healing in both nondiabetic and diabetic mice. MATERIALS AND METHODS: Surgical outcomes were tested using the McFarlane flap in nondiabetic and streptozotocin-induced diabetic mice. Short-term dietary preconditioning included 1 wk of PR or MR diet (1-2 wk) versus an isocaloric complete diet before surgery; all mice were returned to a complete diet postoperatively. Outcome measures of flap wound recovery included skin viability and laser Doppler imaging of flap perfusion and assessment of CD45+ cell infiltration. Glucose homeostasis was assessed by glucose tolerance testing and by perioperative glucose levels in the diabetic cohort. RESULTS: No significant differences were observed in percentage of viable skin, perfusion, or immune cell infiltration at 7-10 d after surgery in PR or MR mice compared with controls in healthy or diabetic mice. Preoperative glucose tolerance and postoperative glucose levels were however significantly improved by both PR and MR in diabetic mice. CONCLUSIONS: Short-term dietary preconditioning with PR or MR did not impair wound healing in nondiabetic or diabetic mice. However, both regimens reduced preoperative hyperglycemia in diabetic mice. Thus, brief preoperative dietary manipulations stand as strategies to potentially improve perioperative hyperglycemia with no deleterious effects on wound healing in mice.
BACKGROUND: Dietary restriction (DR), defined as reduced nutrient intake without malnutrition, is associated with longevity extension, improved glucose metabolism, and increased stress resistance, but also poor wound healing. Short-term preoperative DR followed by a return to normal feeding after surgery results in improved surgical outcomes in preclinical models. However, the effect of preoperative DR on wound healing and perioperative glucose homeostasis is currently unknown. Here, we tested the effects of two different preoperative DR regimens-protein restriction (PR) and methionine restriction (MR)-on wound healing and perioperative glucose homeostasis using an established murine model of wound healing in both nondiabetic and diabeticmice. MATERIALS AND METHODS: Surgical outcomes were tested using the McFarlane flap in nondiabetic and streptozotocin-induced diabeticmice. Short-term dietary preconditioning included 1 wk of PR or MR diet (1-2 wk) versus an isocaloric complete diet before surgery; all mice were returned to a complete diet postoperatively. Outcome measures of flap wound recovery included skin viability and laser Doppler imaging of flap perfusion and assessment of CD45+ cell infiltration. Glucose homeostasis was assessed by glucose tolerance testing and by perioperative glucose levels in the diabetic cohort. RESULTS: No significant differences were observed in percentage of viable skin, perfusion, or immune cell infiltration at 7-10 d after surgery in PR or MR mice compared with controls in healthy or diabeticmice. Preoperative glucose tolerance and postoperative glucose levels were however significantly improved by both PR and MR in diabeticmice. CONCLUSIONS: Short-term dietary preconditioning with PR or MR did not impair wound healing in nondiabetic or diabeticmice. However, both regimens reduced preoperative hyperglycemia in diabeticmice. Thus, brief preoperative dietary manipulations stand as strategies to potentially improve perioperative hyperglycemia with no deleterious effects on wound healing in mice.
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