PMID- 37764859 OWN - NLM STAT- MEDLINE DCOM- 20230929 LR - 20231003 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 15 IP - 18 DP - 2023 Sep 20 TI - Caloric Restriction: A Novel Conditioning Strategy to Improve the Survival of Ischemically Challenged Musculocutaneous Random Pattern Flaps. LID - 10.3390/nu15184076 [doi] LID - 4076 AB - Caloric restriction (CR) is a cost-effective and easy-to-perform approach to counteracting surgical stress. The present study therefore evaluates the tissue-protective effects of a 30% CR in musculocutaneous flaps undergoing ischemia. For this purpose, a well-established murine dorsal skinfold chamber model, in combination with random pattern musculocutaneous flaps, was used. C57BL/6N mice were divided at random into a CR group (n = 8) and a control group with unrestricted access to standard chow (n = 8). The CR animals were subjected to a 30% reduction in caloric intake for 10 days before flap elevation. Intravital fluorescence microscopy was carried out on days 1, 3, 5, 7 and 10 after flap elevation to assess the nutritive blood perfusion, angiogenesis and flap necrosis. Subsequently, the flap tissue was harvested for additional histological and immunohistochemical analyses. The CR-treated animals exhibited a significantly higher functional capillary density and more newly formed microvessels within the flap tissue when compared to the controls; this was associated with a significantly higher flap survival rate. Immunohistochemical analyses showed a decreased invasion of myeloperoxidase-positive neutrophilic granulocytes into the flap tissue of the CR-treated mice. Moreover, the detection of cleaved caspase-3 revealed fewer cells undergoing apoptosis in the transition zone between the vital and necrotic tissue in the flaps of the CR-treated mice. These results demonstrate that a CR of 30% effectively prevents flap necrosis by maintaining microperfusion on a capillary level and inhibiting inflammation under ischemic stress. Hence, CR represents a promising novel conditioning strategy for improving the survival of musculocutaneous flaps with random pattern perfusion. FAU - Weinzierl, Andrea AU - Weinzierl A AUID- ORCID: 0000-0003-2449-2698 AD - Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany. AD - Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland. FAU - Coerper, Maximilian AU - Coerper M AD - Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany. FAU - Harder, Yves AU - Harder Y AUID- ORCID: 0000-0002-2557-249X AD - Department of Plastic, Reconstructive and Aesthetic Surgery, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland. AD - Faculty of Biomedical Sciences, Universita della Svizzera Italiana, 6900 Lugano, Switzerland. FAU - Menger, Michael D AU - Menger MD AUID- ORCID: 0000-0002-9670-7961 AD - Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany. FAU - Laschke, Matthias W AU - Laschke MW AUID- ORCID: 0000-0002-7847-8456 AD - Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany. LA - eng PT - Journal Article DEP - 20230920 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 SB - IM MH - Animals MH - Mice MH - Mice, Inbred C57BL MH - *Caloric Restriction MH - *Energy Intake MH - Apoptosis MH - Necrosis PMC - PMC10536342 OTO - NOTNLM OT - angiogenesis OT - caloric restriction OT - dietary restriction OT - dorsal skinfold chamber OT - intravital fluorescence microscopy OT - microcirculation OT - necrosis OT - nutrition OT - random pattern flap COIS- The authors declare no conflict of interest. EDAT- 2023/09/28 06:42 MHDA- 2023/09/29 06:44 PMCR- 2023/09/20 CRDT- 2023/09/28 01:36 PHST- 2023/08/26 00:00 [received] PHST- 2023/09/14 00:00 [revised] PHST- 2023/09/19 00:00 [accepted] PHST- 2023/09/29 06:44 [medline] PHST- 2023/09/28 06:42 [pubmed] PHST- 2023/09/28 01:36 [entrez] PHST- 2023/09/20 00:00 [pmc-release] AID - nu15184076 [pii] AID - nutrients-15-04076 [pii] AID - 10.3390/nu15184076 [doi] PST - epublish SO - Nutrients. 2023 Sep 20;15(18):4076. doi: 10.3390/nu15184076.