Summary
It has been shown that pre- and postconditioning of ischemically challenged tissue
with erythropoietin (EPO) is able to reduce necrosis in a dose-dependent manner. The
aim of this study was to determine the tissue-protective effects of different EPO
dosages and administration regimes.
Three groups of six C57Bl/6-mice each were analyzed: (1) pre- and postconditioning
with initial high doses of EPO (starting at 2500 I.U./kg bw i.p.) followed by low
doses of EPO (125 I.U./kg bw i.p.) (EPO-high-dose); (2) pre- and postconditioning
with low doses of EPO (125 I.U./kg bw i.p.) (EPO-low-dose); and (3) untreated control
group. Randomly perfused musculocutaneous flaps were mounted on dorsal skinfold chambers
undergoing acute persistent ischemia and developing ∼50% necrosis without treatment.
Intravital epifluorescence microscopy was performed at days 1, 3, 5, 7, and 10 after
surgery, assessing flap necrosis, microcirculation, and angiogenesis. The hematocrit
was measured at days 0, 3, 7, and 10.
Only the EPO-low-dose regimen was associated with a significant reduction of necrosis
when compared to untreated controls. EPO-low-dose showed a higher increase in both
arteriolar diameter and velocity, thereby resulting in a significantly increased arteriolar
blood flow and a hence higher functional capillary density (FCD) of the critically
perfused zone. EPO-induced angiogenesis was significantly increased in EPO-low-dose
at days 7 and 10. Only EPO-high-dose reached a significant hematocrit increase by
day 10.
Tissue pre- and postconditioning with low doses of EPO protects the critically perfused
musculocutaneous tissue by maintaining capillary perfusion because of increased arteriolar
blood flow mediated by nitric oxide (NO) expression.
Keywords
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Article info
Publication history
Published online: January 09, 2019
Accepted:
January 6,
2019
Received in revised form:
November 12,
2018
Received:
February 11,
2018
Identification
Copyright
© 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
