title: Hypoxic preconditioning increases skin oxygenation and viability but does not alter VEGF expression or vascular density.
abstract: Intermittent hypoxia is known to elicit adaptive changes that increase tissue oxygen delivery. We investigated the effects of intermittent hypoxic exposure (IHE) in normal skin (course study) and evaluated whether preoperative IHE-preconditioning alleviates acute ischemic injury in skin flaps (flap study). For 4 weeks, 55 rats were exposed to a daily IHE-session (6 hypoxic cycles, 9% O(2), 6 to 10 min) separated by 3 min of reoxygenation (20.9% O(2)). The time course of intracutaneous PO(2) was measured at weekly intervals. VEGF/VEGF-receptor-mRNA and vascular density were measured in normal skin before and after 1, 2, 3, and 4 weeks of the IHE course (20 rats). In 35 rats, skin flaps were elevated after IHE and similar studies were undertaken in samples from 3 flap areas at postoperative days 0.5, 2, and 4. Additionally, flap survival and cutaneous blood flow were quantitated. In normal skin, PO(2) was initially significantly decreased during the hypoxic cycles (PO(2) 4.1 +/- 1.5 mmHg). After 4 weeks of IHE, PO(2) (34.5 +/- 5.8 mmHg) was maintained even under hypoxic conditions. In flaps, IHE led to a 2.6-fold increase in PO(2), increased flap survival (+ 19.4%, day 7), and blood flow (+ 19.1%, day 10) (p < 0.01). In neither study did IHE-preconditioning increase VEGF/VEGF-receptor-mRNA expression or vascular density. We conclude that (1) IHE induces pronounced hypoxia in the skin, but progressive adaptation occurs within 4 weeks, (2) preoperative IHE-preconditioning leads to significantly higher PO(2), blood flow, and tissue survival in ischemic skin flaps, and (3) the transient hypoxia induced by IHE does not alter expression of VEGF or its receptors nor does it trigger angiogenesis.
authors.affiliation: Plastic & Reconstructive Surgery Unit, University Hospitals of Geneva, Switzerland.
authors.forename: Kai U
authors.initials: KU
authors.lastname: Schlaudraff
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
authors.forename: Elena N
authors.initials: EN
authors.lastname: Tkatchouk
authors.forename: Igor
authors.initials: I
authors.lastname: Ehrenburg
authors.forename: Navid
authors.initials: N
authors.lastname: Alizadeh
authors.forename: Denys
authors.initials: D
authors.lastname: Montandon
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pittet
mesh_terms: D000064:Acclimatization; D000818:Animals; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013524:Surgical Flaps / Q000098:blood supply; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
chemical_list: D042442:Vascular Endothelial Growth Factors