Improved Free Musculocutaneous Flap Survival with Induction of Heat Shock Protein

Abstract

The cellular response to a wide variety of stresses results in the synthesis of a family of stress response proteins termed heat shock proteins. Recent studies have demonstrated that heat shock proteins produced in response to an initial stress seem to protect against subsequent unrelated stresses. Importantly, hyperthermia-induced heat shock proteins provided protection from ischemia/reperfusion injury in several organ transplantation models. We hypothesized that free musculocutaneous flap survival could be improved by enhancing the flap's tolerance to relative ischemia by the prior induction of heat shock proteins. Accordingly, we determined the heat shock protein response in skin and muscle after systemic or local heating and examined the effect on free musculocutaneous flap survival in a rat model. Free musculocutaneous flaps incorporating thigh adductor muscles and a 2 x 6-cm2 skin paddle were transplanted to the ipsilateral groin in three groups of male Wistar rats. Systemically heated rats (n = 6) were anesthetized and incubated for 30 minutes at 42 degrees C 6 hours before free musculocutaneous tissue transfer. Locally heated rats (n = 6) were anesthetized, and their donor site anterior thigh was placed for 30 minutes on a heating block set at 44 degrees C 6 hours before free tissue transfer. Control rats (n = 5) did not have heating pretreatment but underwent identical anesthesia. Animals were sacrificed on postoperative day 3, at which time skin loss (cm2) and muscle viability, quantified by nitroblue tetrazolium staining time, were assessed in a blinded fashion. The skin and muscle from the free flap were analyzed for HSP72 mRNA and protein using quantitative Northern and Western blot techniques. All free musculocutaneous flaps were viable. However, the locally and systemically heated rats demonstrated a marked improvement of skin survival, which correlated with increased skin levels of HSP72. There were no differences in nitroblue tetrazolium muscle staining times or muscle levels of HSP72 among the three groups. These findings suggest that prior heat-induced heat shock proteins result in improvement in musculocutaneous flap survival, which may have direct clinical applications, especially in high-risk patients.

Pharmacologic Preconditioning of Random-Pattern Skin Flap in Rats Using Local Cyclosporine and FK-506

“…[1][2][3][4][5][6] The IPC phenomenon was first described in heart by Murry et al 2 Similar results were reported for other organ systems, for example liver 23 and kidney. 24 Various factors such as heat-shock proteins, 25,26 adenosine, 27,28 cyclooxygenase, 29 bradykinin, 30 and endogenous opioid system 3 seem to be involved in the IPC mechanism. NO, 28,31,32 ATP-sensitive K ϩ channels, 22,[33][34][35]15 are probably the more emphasized players in the scenario.…”

Die Apoptose und ihre Bedeutung in der Plastischen Chirurgie

“…Eine positive Korrelation mit dem Überleben von Lappenplastiken konnte ebenso für die Expression von Hitze-Schock-Proteinen, sog. "heat-shock proteins" (HSPs), beobachtet werden, die bei der hyperthermischen Präkonditionierung von Lappenplastiken induziert wird [62]. Für HSP72 beispielsweise konnte eine Inhibition von Apoptose nachgewiesen werden [7].…”

Stress response of systemic organs to ischemia-reperfusion of rat hind limb – study of induction of 72-kD stress protein (HSP72)

“…There have also been several studies on HSP72 induction relating to the ischemic condition of various organs including the skeletal muscle [7,16] and skin [17,31] that are among the ischemic organs in ischemia of the lower leg.…”