Isolated perfused porcine skin flap

Further specimens in use are the perfused cow udder, the porcine forelimb, and the isolated perfused porcine skin flap (IPPSF) [55-57], While the first two require the sacrifice of the animal, the last one can be isolated surgically from the abdomen of the pigs, which afterwards can be returned to their prior disposition [49],... 

J. E. Riviere, K. F. Bowman, and N. A. Monteiro-Riviere. The isolated perfused porcine skin flap (IPPSF). I. A novel in vitro model for percutaneous absorption and cutaneous toxicology studies. Fundam. Appl. Toxicol. 7 444—453 (1986). 

Wester RC, Melendres J, SedikL, et al. 1998. Percutaneous absorption of salicylic acid, theophylline, 2,4-dimethylamine, diethyl hexyl phthalic acid, and />-aminobenzoic acid in the isolated perfused porcine skin flap compared to man in vivo. Toxicol Appl Pharmacol 151 159-165. 

Figure 35.5. Light micrograph of an isolated perfused porcine skin flap irradiated with 1260mJ/cm2 depicting sunburn cells in the stratum basale layer (arrows) (560x). (Source Modified from Monteiro-Riviere, N. A., et al., Photodermatol. Photoimmunol. Photomed. 10, 235-243,1994.)...

Riviere et al. (1999) used the isolated perfused porcine skin flap model to study absorption and disposition of JP-8. The percutaneous absorption and cutaneous disposition of topically applied neat Jet-A and JP-8 jet fuels were assessed by monitoring the absorptive flux of the marker components 14C naphthalene and 3H dodecane simultaneously. Absorption of 14C hexadecane was estimated from JP-8. Data were not reported in absolute amounts or concentrations. Instead, the objectives were to determine the relative absorption of the individual marker components from jet fuel, and the effect of a specific jet fuel s composition on the absorption of a specific marker. Having evaluated the absorption of only three of the 228 major nonadditive hydrocarbon constituents of the fuels, the authors stated that this is insufficient information to conduct risk assessments on jet fuels. However, the authors conclusions are informative. Naphthalene penetrated the skin more rapidly than dodecane or hexadecane, but the latter compounds had a larger fraction of the dose deposited in the skin. There were also differences in naphthalene and dodecane absorption and skin deposition between the fuels. These findings reinforce the difficulty of predicting risk for complex mixtures such as jet fuels. 

Monteiro-Riviere, N.A., King, J.R., Riviere, J.E. (1990). Cutaneous toxicity of mustard and lewisite on the isolated perfused porcine skin flap. Pentagon Reports. North Carolina State University at Raleigh, School of Veterinary Medicine, Raleigh, NC, 144 pp. 

Riviere, J.E. Monteiro-Riviere, N.A. Wilhams, P.L. The isolated perfused porcine skin flap as an in vitro model for predicting transdermal pharmacokinetics. Eur. J. Phar-mac. Biopharmac. 1995, 41, 152-162. 

There are several perfused skin preparations with an intact functional microvasculature. The major advantage of such a perfused system is that subsequent systemic influences on absorbed chemical are not present, yet the tissue is fully functional with an intact microcirculation unlike simpler in vitro models. The perfused rabbit ear model, perfused pig ear model, in situ sandwich skin flap in athymic rats, and the hybrid rat-human sandwich flap have been developed [8], but each intuitively has severe limitations. The isolated perfused porcine skin flap (IPPSF) developed in our laboratory is a unique ex vivo skin preparation that has an intact functional cutaneous microcirculation. Predictions from IPPSF studies have correlated well with in vivo absorption... 

Riviere JE, Williams PL, Hillman R, Mishky L. Quantitative prediction of transdermal iontophoretic delivery of arbutamine in humans using the in vitro isolated perfused porcine skin flap (IPPSF). J Pharm Sci 1992 81 504-7. 

Rogers, R. A., and J. E. Riviere. 1994. Pharmacological modulation of the cutaneous vasculature in the isolated perfused porcine skin flap./. Pharm. Sci. 83 1682-1689. 

Figure 2 Cutaneous efflux profile of topically applied carbaryl (40 mcg/cm ) in the isolated perfused porcine skin flap. Mean +. S.E., n=4...

Isolated perfused skin models, such as the isolated perfused porcine skin flap (IPPSF) developed in our laboratory, may be the missing link in the hierarchy of classic in vitro and in vivo models. Primary advantages of isolated perfused systrans include the following ... 

Figure 3.1 Two-stage surgical procedure used to create isolated perfused porcine skin flaps.

Bowman, K.F., Monteiro-Riviere, N.A., and Riviere, J.E., 1991, Development of surgical techniques for preparation of in vitro isolated perfused porcine skin flaps for percutaneous absorption studies. Am. J. Vet. Res., 25 75-82. 

Carver, M.P., Williams, PL., and Riviere, J.E., 1989, The isolated perfused porcine skin flap (IPPSF). 111. Percutaneous absorption pharmacokinetics of organophosphates, steroids, benzoic add and caffeine, Toxicol Appl Pharmacol, 97 324—337. 

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