Isolated extremity perfusion

Pharmacokinetic Principles 33 Dose-Response Relationship 34 Intraperitoneal Application 34 Intra-arterial Application 34 Isolated Perfusion Techniques Application Techniques 35 Intracavitary Application 35 Intra-arterial Infusion 36 Regional Perfusion Techniques Stop-Flow Perfusions 36 Isolated Extremity Perfusion (ILP) 37 Hyperthermic Peritoneal Perfusion (HIPEC) 38 Clinical Indications 38 Pancreas Carcinoma 38 Bronchial Carcinoma 39 Extremity Sarcoma 40 Peritoneum 41 Surgical Technique 41 Rationale 42 Clinical Results 43 References 44 Further Reading 45... 

The technique of isolated extremity perfusion (ILP) was established by Creech and Krementz in 1958 (Creech et al. 1958). Isolation of extremity is achieved hy cross-clamping major vessels, cannulation of artery and vein and connection to an extracorporeal circuit (Fig. 2.4.5). To minimize... 

The exclusive role of the liver in the biosynthesis of fibrinogen, questioned by some, has been reaffirmed in isolated liver perfusion experiments in which maximal net biosynthesis of fibrinogen of 0.6 mg. per hour per gram wet weight of liver occurs. This approximates three to four times the normal rate of fibrinogen biosynthesis in turnover in the intact normal rat and occurs only in liver perfusions in which the stimulus of extreme hypofibrinogenemia associated with the use of completely defibrinated blood is present. 

Hoekstra HJ, Meller I, Nieweg OE, Kettelhack C, Ben-Ari G, Pector JC, Lejeune FJ. Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience. Ann Surg 1996 224(6) 756- 5. 

Drouet A, Le Moigne F, Have L, Blondet R, Jacquin O, Chauvin F. Common peroneal nerve palsy following TNF-based isolated limb perfusion for irresect-able extremity desmoid tumor. Orthop Traumatol Surg Res 2009 95(8) 639-44. 

Nitric oxide release from blood vessels was first detected by chemiluminescence (Palmer et ai, 1987). In the original adaptations of the nitric oxide detector, perfusates from isolated vessels were directly mixed in a reflux chamber containing acetic acid and iodine. The iodine in the reflux chamber served to reduce any nitrites or nitroso-containing groups to nitric oxide, which was stripped from the chamber by a continuous stream of nitrogen or helium that flowed to the chemiluminescent detector. Replacement of the acetic acid with the less volatile trichloroacetic acid reduces problems with contamination of the nitric oxide detector (Dr. D. Harrison, Emory University, Atlanta, Georgia, personal communication, 1991). While extremely sensitive, the use of the acid reflux chamber also reduces the specificity of the assay, raising questions as to whether nitric oxide or a nitrosothiol is EDRF (Myers et ai, 1990). 

About 100 ml of perfusion medium is re-used over a period of 2 days before it and the extracapillary medium are changed. The cells remain healthy for a month or more and three small capillary beds in parallel will produce over 2 x 108 cells. This method is extremely useful for the production or metabolic conversion of metabolites. Thus human chorionic gonadotropin may be isolated from the perfusate of human choriocarcinoma cells (Odell at al., 1967 Knazek and Gullino, 1973 Knazek et al., 1974). 

Figure 2. Effects of the enterotoxin on perfusates from isolated organs. Symbols used are O, lower extremities liver A, lung.

The question arose next was which organ or tissue is responsible for potassium liberation into the blood in intoxicated animals. To answer the question, we perfused the enterotoxin into isolated organs or tissue. As shown in Fig. 2, concentration of potassium in perfusates from isolated lungs and lower extremities showed no obvious change after the perfusion of the enterotoxin. However, the concentration of potassium in perfusate from isolated liver showed a remarkable increase after the perfusion of the enterotoxin. The leakage of potassium from the liver occurred within a minute and finished 5 min after the perfusion of the toxin (Fig. 3). The amount of the potassium liberated from the liver was estimated to be about 133 pmol, which is enough to raise plasma level of potassium to more than lethal level. In addition, activities of transaminases in the perfusate from the enterotoxin-treated liver increased following to the elevation of potassium concentration (Fig. 3). The results indicated that potassium is liberated from hepatocytes, and that the enterotoxin makes a small pore ... 

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