Salvaging the Zone of Stasis By Simvastatin: An Experimental Study in Rats

Abstract

Salvaging the zone of stasis is important for burn researchers because this can prevent an increase in the depth and width of the injured area. Statin analogues have many pleiotropic effects on the vessel walls and the coagulation and fibrinolytic systems. In this study, we investigated the effects of simvastatin, a statin analogue, administered to rats burned with a metal comb. No treatment was given to the control group (n = 10). Simvastatin was given at a dose of 5 mg/kg/d by intraperitoneal injection in treatment group (n = 10) for 7 days. Phosphate-buffered saline was given 1 mg/kg/d by intraperitoneal injection in sham group (n = 10). The groups were randomly divided into two subgroups (n = 5) for evaluation at 24 hours and 7 days. It was observed that there were necrotic areas and viable interspaces in both the experimental and control groups at 24 hours. The interspaces progressed to necrotic areas in the control and sham groups at 7 days. However, viable interspaces were separated from necrotic areas clearly in the treatment group at 7 days. In the samples taken from interspaces at 24 hours, positive staining for thrombomodulin (TM) for all groups was noted. In the samples taken from the control and phosphate-buffered saline groups at 7 days, there was negative staining for TM. However, in the samples taken from interspaces of the treatment group, positive staining for TM was observed. The conclusion of this study was that simvastatin potently increased endothelial TM expression in the zone of stasis and preserved the zone.

Validation of a Vertical Progression Porcine Burn Model

“…While deep partial thickness and full-thickness burns described by Cuttle and observed here with 90°C for 20 seconds may not be preventable, full-thickness burns that arise from conversion of mid-dermal partial thickness burns, such as those created with hot bars at 80°C for 20 seconds or 80°C for 30 seconds described here, are potentially preventable. In fact, we 5, 6 and others 24 have shown the ability of a number of therapeutic agents to reduce burn injury progression in the horizontal plane using the comb burn model. We are now planning to evaluate some of the same therapies in the vertical progression model in pigs that we believe more closely reflects what occurs in human burns.…”

A Review of the Local Pathophysiologic Bases of Burn Wound Progression

“…Because thrombomodulin expression was maintained in simvastatin-treated rats, it was concluded that simvastatin protects the zone of stasis from necrosis through its stimulation of thrombomodulin expression. 90 Instead of targeting the restoration of the body's intrinsic antithrombotic, profibrinolytic systems, such as thrombomodulin expression, Isik et al have focused on the administration of an exogenous fibrinolytic agent. They studied the ability of recombinant tissue-type plasminogen activator (r-tPA) to maintain the patency of vessels in the zone of stasis and prevent progressive tissue necrosis in a rat comb burn model.…”

Delayed Topical p38 MAPK Inhibition Attenuates Full-Thickness Burn Wound Inflammatory Signaling

“…The apoptotic cells in the zone of stasis that surround burn injuries usually die over a period of 2–3 days post injury with progressive increase in the wound depth (37). If the hair-cell follicles are well preserved without apoptosis, the burn wound is considered partial –thickness (38). To diagnose the depth of the wound, several methods have been advocated, and investigating the apoptotic status of the hair-cell follicles is one such method that is accepted in the experimental studies (39).…”