The isolated blood-perfused pig ear: an inexpensive and animal-saving model for skin penetration studies.
To overcome most of the disadvantages of current models to investigate percutaneous penetration of drugs or toxic substances, a model is proposed here based on the isolated pig ear, which is obtained at the slaughterhouse, and perfused with oxygenated blood from the same pig. To determine the viability of the preparations, we measured glucose consumption and lactate production as metabolic parameters, Na+ and K+ ions, as well as lactate dehydrogenase activity in blood as markers for cell damage, whereas vasomotor reactivity was assessed by administering noradrenaline and isoxsuprine. After 60 min of equilibration, only insignificant changes in these parameters were observed during the subsequent 3-hr test period (longer periods were not tested). A slight weight increase was noted during the total period 4 hr, presumably due to slight edema formation. On the basis of several types of measurements, such as in vivo blood flow and ear temperature and in vitro glucose metabolism, standard procedures were developed. It is concluded that this technique offers an easy to handle, cost-efficient, and animal-saving model for skin penetration studies that lacks most of the disadvantages of existing models.
de Lange
J
J
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
van Eck
P
P
Elliott
G R
GR
de Kort
W L
WL
Wolthuis
O L
OL
D000826:Animal Testing Alternatives; D000818:Animals; D001769:Blood; D001786:Blood Glucose / Q000378:metabolism; D003365:Costs and Cost Analysis; D004431:Ear, External / Q000098:blood supply / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008954:Models, Biological; D009994:Osmolar Concentration; D010477:Perfusion; D011188:Potassium / Q000097:blood; D012869:Skin Absorption; D012964:Sodium / Q000097:blood; D013552:Swine; D013997:Time Factors; D014116:Toxicology / Q000191:economics / Q000379:methods; D014661:Vasoconstriction
D001786:Blood Glucose; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D011188:Potassium