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Krauss et al. Plast Aesthet Res 2018;5:39 I http://dx.doi.org/10.20517/2347-9264.2018.41 Page 3 of 10

Table 1. Different ways of tissue conditioning
Tissue conditioning
Surgical delay
Ischemic preconditioning
Remote ischemic preconditioning
Thermic preconditioning
Growth factors
Extracorporeal shock waves
Stemm cells
Pharmaceutical preconditioning

Surgical delay
Surgical delay is the predecessor of modern preconditioning techniques. By raising the flap itself without
severing its pedicle, the vessels along the axis of the flap reorganize and increase in size, leading to a better
perfusion of the distal flap due to a dilation of linking and choke vessels, causing a connection of adjacent
vascular territories which could be demonstrated in animal models as well as in humans [31,32] . Direct linking
vessels have a large caliber and connect adjacent vascular territories by connecting perforators themselves,
while indirect linking vessels, also known as choke vessels, connect vascular territories via recurrent flow
through the subdermal plexus [33,34] . The mechanisms behind this are still not fully understood but there are
many animal studies that could show neovascularisation, vasodilation and reorganization of vessels due to
surgical delay [35-37] . Although surgical delay proved to increase flap perfusion and therefore increased the
survival of flaps in the clinical setting [38,39] , there are also major disadvantages to this strategy, especially the
need for additional surgery and its risks for the affected patients as well as increased health care costs due
to longer hospital stays. Especially in TRAM flaps surgical delay was used but due to the improvement of
microsurgical methods free flaps as the DIEP flap have become a safer and more often applied alternative with
less donor side morbidity [40-42] .

Ischemic preconditioning
[43]
Ischemic preconditioning was introduced by Mounsey et al. for conditioning of the myocardium, but has
since been applied to different fields of surgery including flap surgery. Murry et al. and Jennings et al. [45]
[44]
found that brief, intermittent cycles of ischemia have a protective effect on the myocardium resulting in a
delay or even protection of lethal injury to the myocardial cells due to metabolic changes in the affected
cells in a dog model. Various animal studies showed, that ischemic preconditioning leads to an increase
in capillary perfusion, the vascular response to changes in perfusion pressure, a decrease in leukocyte-
mediated reperfusion injury, an increase of critical ischemia time tolerated by the affected tissue, a decrease
of vasospasms as well as a decrease in the capillary no-reflow phenomenon [46-49] . All of these mechanisms lead
[48]
to a significant decrease in flap necrosis in skin flaps as well as in muscle flaps . Because of these positive
effects, the ideal application of ischemic preconditioning was examined as well. It was found that three cycles
of ischemic preconditioning of 10 min each are superior to the application of only one or two cycles. They also
found that a cycle of 10 min of ischemia is superior to 5 min of ischemia . It could also be shown that there is
[50]
no difference in the positive effect of ischemic preconditioning on reducing muscle flap necrosis whether it is
[51]
applied 24 h or immediately before flap elevation . Interestingly, ischemic preconditioning has immediate as
well as late protective effects: the immediate effect is an improvement of the blood flow hemodynamics and an
attenuation of the leukocyte-mediated reperfusion injury whereas after 24 h of reperfusion the improvement
[46]
of the hemodynamics has subsided while the protective effect against reperfusion injury was still present .
Although there are those numerous positive effects of ischemic preconditioning it hasn’t found its way into
clinical routine use. The main reason for this might be the additional time needed for preparing the pedicle
and applying ischemia prior to flap elevation as well as the spreading of new techniques like indocyanine