Table 3 Angiogenic therapies
From: Pharmacological and cell-based treatments to increase local skin flap viability in animal models
Pharmacologic therapy | MoA | RoA studied | Animal model | Treatment protocol | References |
|---|---|---|---|---|---|
The tetrapeptide acetyl-serine-aspartyl-lysine-proline | Regulation of hematopoiesis peptide | Subdermal injection | Rat dorsal and abdominal skin flaps | Post-operative injections, twice a day for 3Â days | Fromes et al. [30] |
VEGF | Stimulation of angiogenic growth factors, angiogenesis, vascular permeability. Inhibition of apoptosis in endothelial cells | Subdermal injection | Rat dorsal pedicled skin flaps | Pre-operative injections, once daily, 7Â days | Vourtsis et al. [31] |
Basic fibroblast growth factor | Stimulation of angiogenic growth factors, angiogenesis, and arteriogenesis | Gene transfer | Rat dorsal axial skin flap | Pre-operative injection of bFGF gene plasmid vector and electroporation 2Â days | Fujihara et al. [32] |
Epigallocatechin gallate | Enhancement of prostaglandin F2a–induced VEGF synthesis, and protein kinase/c-jun N-terminal kinase | Injection into the interspace between the dermal tissue and subcutaneous membrana carnosa or topical application | Rat dorsal skin flap |  + Local injection five times just before flap elevation  + Topical application to the flap just before flap elevation | Cheon et al. [33] |
Memantine | An N-methyl-D-aspartate (NMDA) receptor antagonist used primarily in the treatment of Alzheimer's disease Upregulation of VEGF | Intraperitoneal injection | Rat random skin flap | Daily post-operative injections for 7Â days | Fan et al. [2] |
Polydeoxyribonucleotide | Upregulation of VEGF | Subdermal or intraperitoneal injection | Rat dorsal skin flap | Subdermal injections distributed evenly in the 12 areas at proximal, middle, and distal areas of the flap 2 days before surgery and immediately after the flap elevation intraperitoneal administration POD 1–10, | Lee et al. [34] |
Calcitriol | An active form of vitamin D. Upregulation of VEGF and enhancement of endothelial cell proliferation and migration | Intraperitoneal injection | Rat McFarlane skin flaps | Daily post-operative injections for 7Â days | Zhou et al. [27] |
Atorvastatin | A statin medication Upregulation of VEGF, bFGF, interleukin-8, angiopoietin Ang-1, Ang-2, eNOS, and hemoxidase (HO)-1. Inhibition of endothelial cells apoptosis | Oral | Rat caudally based McFarlane dorsal skin flaps | Post-operative oral administration by feeding lavage for 7Â days | Chen et al. [35] |
Vinpocetine | Upregulation of VEGF | Celiac injection | Rat McFarlane flap | Daily post-operative injections for 7Â days | Xiao et al. [36] |