Rat Skin Flap Model Research Articles

Evaluation of pedicled skin flap viability by pH, temperature and fluorescein: an experimental study

In order to test methods of predicting skin flap viability, a skin flap model in Sprague-Dawley rats was established. As criteria for studying skin flap survival, we compared measurement of skin pH, temperature, as well as fluorescence photography and computer aided digital morphometry (CADM). Ninety male Sprague-Dawley rats were divided into three groups in which pedicles were clamped for 10, 15, or 20 h. A standardized bipedicled skin flap was prepared, maintained by the epigastric artery, vein and nerve. All flaps were sutured back in place immediately after clamping. We found that postoperative prediction of flap survival based solely upon external appearance was impossible until the 2nd postoperative day. Changes in pH were not statistically significant in the prediction of vital or necrotic flaps. The temperature measurements showed, that in the event of viability the decrease in flap temperature versus the reference temperature (rectal temperature) was significant (P < 0.0094 in Group II, 15 h of ischaemia) or at least a tendency to significance (P < 0.059 in Group III, 10 h of ischaemia) bigger than in the event of partial or total flap necrosis. The photographic documentation using fluorescein showed that all coloured areas survived. Group I (20 h) showed predominantly total flap necrosis. Most flaps in Group III (10 h) exhibited a small necrotic area at the tip. In Group II (15 h) no typical staining pattern could be observed. Furthermore, computer aided digital morphometry demonstrated a decrease of the necrotic area by 7% between the 2nd and 4th postoperative day in Groups II and III. The method which gave the most exact prediction about viability was the fluorescein staining of the flaps via the tail vein.

Evaluation of a continuous systemic infusion of iloprost, a stable PGI-2 analog, on the survival of experimental skin flaps.

Numerous investigators have attempted to enhance the survival of ischemic experimental skin flaps using various pharmacologic manipulations. Recently, the authors' laboratory demonstrated the beneficial effect of iloprost, a stable PGI2 analogue, as a post-ischemic perfusion washout, in improving the survival of ischemic skin flaps. The rat unilateral abdominal skin flap, based on the superficial epigastric vessels, was utilized in this study involving 30 animals. The animals were divided into three different treatment groups, with ischemic periods of 16 and 18 hr. Perfusion washouts were performed at the completion of the various ischemic periods. Alzet osmotic pumps were used to deliver a continuous systemic infusion of iloprost for 7 days postoperatively. The groups consisted of the following: Group 1 (single ILO)--perfusion washout with iloprost only; Group 2 (continuous LD ILO)--low-dose systemic iloprost infusion (0.066 mcg/kg/min) and perfusion washout with iloprost; and Group 3 (continuous HD ILO)--high-dose systemic iloprost infusion (0.1 mcg/kg/min) and perfusion washout with iloprost. The percentage of flap survival was assessed on postoperative day 7. Skin flaps of the animals receiving the continuous systemic infusion of iloprost were noted to have varying percentages of survival, while skin flaps undergoing perfusion washout only were found to have either complete survival using a continuous systemic infusion of iloprost, compared to iloprost perfusion washout alone. In addition, the hypotensive side effects of systemic iloprost infusion limit its use in the rat skin-flap model.

Platelet-derived growth factor BB induces functional vascular anastomoses in vivo.

Neovascularization that generates collateral blood flow can limit the extent of tissue damage after acute ischemia caused by occlusion of the primary blood supply. The neovascular response stimulated by the BB homodimeric form of recombinant platelet-derived growth factor (PDGF-BB) was evaluated for its capacity to protect tissue from necrosis in a rat skin flap model of acutely induced ischemia. Complete survival of the tissue ensued, when the original nutritive blood supply was occluded, as early as 5 days after local PDGF-BB application, and the presence of a patent vasculature was evident compared to control flaps. To further evaluate the vascular regenerative response, PDGF-BB was injected into the muscle/connective tissue bed between the separated ends of a divided femoral artery in rats. A patent new vessel that functionally reconnected the ends of the divided artery within the original 3- to 4-mm gap was regenerated 3 weeks later in all PDGF-BB-treated limbs. In contrast, none of the paired control limbs, which received vehicle with an inactive variant of PDGF-BB, had vessel regrowth (P < 0.001). The absence of a sustained inflammatory response and granulation tissue suggests locally delivered PDGF-BB may directly stimulate the angiogenic phenotype in endothelial cells. These findings indicate that PDGF-BB can generate functional new blood vessels and nonsurgically anastomose severed vessels in vivo. This study supports the possibility of a therapeutic modality for the salvage of ischemic tissue through exogenous cytokine-induced vascular reconnection.

Role of Vitamin E in Ischaemic Skin Flap Survival in Rats

SummaryThe efficacy of free radical scavenger – Vitamin E (VE) in salvage of ischaemic skin flaps was studied in an experimental rat skin flap model. The animals were divided into two groups – a control group (N=15) who did of receive VE and a test group (N=15) who received VE starting one week preoperatively. No significant difference was found in flap necrosis between the control group (38.365% ± 1.398% SEM) and the test group (35.288% ± 0.635% SEM), which received therapeutic dose of VE (100 mg/kg/day. 1 mg = 1.49 I.U). Further research is needed to establish the role of vitamin E as an agent of ischaemic skin flap salvage.

A randomised controlled study to evaluate the effect of Naftidrofuryl in a rat ischaemic skin flap model

The theoretical benefit of Naftidrofuryl in improving survival of ischaemic skin flaps was tested in a randomised controlled study using oral, intraperitoneal and local administration of the drug in three groups of Wistar rats. The vasodilator Naftidrofuryl was shown to be of no value in preventing distal necrosis in a rat skin flap model which has previously responded to pharmacological manipulation.

Percutaneous and systemic disposition of hexamethylene lauramide and its penetration enhancement effect on hydrocortisone in a rat sandwich skin-flap model.

The percutaneous absorption and distribution profile of hexamethylene lauramide (hexahydro-1-lauroyl-1H-azepine) were examined using a rat skin-flap model. After a topical dose to the skin flap, the drug concentrations in the vasculature at the site of drug application and in the systemic blood were monitored simultaneously. Hexamethylene lauramide penetrated the skin and reached a steady state in stratum corneum, viable epidermis, dermis, and cutaneous blood in 3 hr. Its concentration in the skin was much higher than that in the blood. Its apparent concentration in the epidermis was 19 times that in the dermis and about 3000 times that in the cutaneous blood. The percutaneous absorption of 14C-hexamethylene lauramide resulted in ascending systemic blood concentrations throughout the experimental period, whereas the cutaneous blood levels remained steady. The topically absorbed hexamethylene lauramide was quantitatively recovered in urine (85%) and feces (13%). The half-lives of urinary and fecal excretion of 14C-hexamethylene lauramide were 17 and 30 hr, respectively. Hexamethylene lauramide, when topically coadministered in an experimental formulation, enhanced the skin penetration of hydrocortisone with increased drug contents in the stratum corneum (2-fold) and with increased hydrocortisone concentrations in the cutaneous blood (3.4-fold) and the systemic blood (3.5-fold). The results indicated that the high concentration and retention of hexamethylene lauramide in stratum corneum and viable epidermis may contribute to its penetration enhancement effect in the skin. A steady state in percutaneous tissues was observed before the drug reached distribution equilibrium systemically. The systemic blood concentration of a topically applied agent therefore may not reflect its percutaneous kinetic processes before a systemic distribution equilibrium is reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical delay and arachidonic acid metabolites: evidence for an inflammatory mechanism: an experimental study in rats

In a rat skin flap model, surgical delay produced an increase in the production of arachidonic acid metabolites, with a derangement of the normal equilibrium between PGE2 and PGF2α and a marked increase in the vasoconstrictive substance, thromboxane. During the delay period, there is a gradual decrease in tissue levels toward normal. Subsequent elevation of the delayed flap produces a blunted response in thromboxane production, an increase in PGE2 levels and increased flap survival. Acute elevation of an undelayed flap produced more marked elevation of all metabolites, with prolonged elevation of the vasoconstrictive PGF2α and thromboxane, progressive ischemia and decreased flap survival. A key role in inflammation, mediated by these inflammatory mediators, is postulated in the mechanism of delay.