Perfused skin

J. E. Riviere. Perfused skin models. In J. E. Riviere (ed.), Dermal Absorption Models in Toxicology and Pharmacology, Taylor Francis Group, Boca Raton, 2006. 

For postmortem analysis, blood and bile are collected at the latest at the time of autopsy. Otherwise, as is true for plasma samples, the most informative results are obtained when blood samples are collected during acute illness or at least prior to a meal (see 3.2.4, subheading Specimen ). Blood should be obtained by capillary stick of well-perfused skin (heels in young infants or fingers) and free dripping of a few drops of blood directly on the filter paper card. Following complete drying at room temperature for at least 3 h, the sample can be sent ambient. Analysis should be... 

The next level of in vitro systems employed is the use of isolated perfused skin flap preparations that are surgically prepared vascularized skin flaps harvested from pigs and then transferred to an isolated organ perfusion chamber. This model allows absorption to be assessed in skin that is viable and anatomically intact and that has a functional microcirculation. Studies conducted to assess the percutaneous absorption of drugs and pesticides in this model compared to humans show a high correlation. Validation of these in vitro methods is a prerequisite for regulatory acceptance. 

King, J.R., Riviere, J.E., Monteiroriviere, N.A. (1992). Characterization of lewisite toxicity in isolated perfused skin. Toxicol. Appl. Pharmacol. 116 189-201. 

Zhang, Z., Montiero-Riviere, N.A. (1997). Comparison of integ-rins in human skin, pig skin, and perfused skin an in vitro skin toxicology model. J. Appl. Toxicol. 17 247-53. 

Monteiro-Riviere, N.A., Inman, A.O. (1995). Indirect immuno-histochemistry and immunoelectron microscopy distribution of eight epidermal-dermal junction epitopes in the pig and in isolated perfused skin treated with bis (2-chloroethyl) sulfide. 

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... 

Monteiro-Riviere NA. The use of isolated perfused skin in dermatotoxicology. In Vitro Toxicol 1993 5 219-33. 

There are several perfused skin preparations with an intact functional microvasculaturc. 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 (Pershing and Krueger, 1987), but each... 

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 ... 

The presentation here provides an overview of tlie uses of a perfused skin model such as the IPPSF in percutaneous absorption and dermatotoxieokinetie studies. One of its major advantages is that both absorption and toxicity may be assessed in the same preparation. The pharmaeokinetic models developed arc experimentally verifiable. The major limitations are centered on the cost of the preparation and the technical expertise required to successfully conduct the studies. The overall cost is significantly greater than in vitro diffusion cell studies or in vivo rodent experiments, comparable to human skin equivalent and larger mammal (dog, pig, primate) in vivo work and much less expensive than human trials. However, cost alone is not a sufficient criterion. These studies are humane more information may be gathered than is obtainable with either in vitro or in vivo work. Optimal benefit may be achieved if these studies serve as a bridge between in vitro human/animal and in... 

Riviere, J.E., Brooks, J.D., and Qiao, G.L., 2000, Methods for assessing the percutaneous absorption of volatile chemicals in isolated perfused skin studies with chloropen-tafluorobenzene (CRFB) and dichlorobenzene (EXIB), Toxicol. Methods, 10 265-281. 

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