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Energy metabolism of healing tissue was studied in experimental wounds of rats chronically breathing 11% O2, air or 55% O2. Increasing oxygen supply elevated both PO2 and PCO2 in the wound tissue. At the early phases of healing hypoxic wounds contained less DNA than normoxic or hyperoxic tissues. In hypoxia the accumulation of wound collagen was clearly retarded. Furthermore, tissue taken from wounds healing in hypoxic environments and tested ex vivo in air showed decreased capacity for glucose utilization, lactate production and oxygen consumption. Concentrations of AMP, ADP and ATP in repair tissue increased as healing progressed. The more oxygen available the higher the amounts of ADP and ATP. The AMP content was not affected by changes in local oxygen tension. These results support the earlier concept that the supply of oxygen in healing tissue may be rate-limitimg. Reduction of available oxygen either by systemic hypoxia or by increased diffusion distance impedes healing.

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Subcutaneous tumors of a patient with v. Recklinghausen's neurofibromatosis contained about 31% collagen calculated on the basis of lipid-free dry weight. Slices of the tumors synthesized collagen at a rate (4.7-8.5% from total protein) which was higher than that of the skin slices (2.8-5.9%). Neurofibromatosis cells were cultured from tumors of two patients. They synthesized relatively much more collagen than cultures of skin fibroblasts of the same patient or of healthy age-matched control persons. The second patient's cultures were studied in detail. The cell densities of these cultures were higher and expressed more variation than the densities of control skin fibroblasts. Ion exchange cellulose chromatograms, SDS-polyacrylamide gel electrophoresis and 3-hydroxyproline analysis of the radioactive proteins made by the cultures indicate that most of the collagenous proteins resembled type I collagen. High proliferative capacity and high collagen synthesis of selected neurofibromatosis cells explains the growth of solid tumors.

This work was prompted by earlier findings of the beneficial effect of increased oxygen supply on wound healing. Enzyme activities in the limiting step of glycolysis, citric acid cycle and pentose phosphate cycle were determined in cellulose sponge implants of rats chronically, breathing 12% O(2), air or 55% O(2.) Respiratory gas tensions and concentrations of pyruvate and lactate were measured in wound fluid aspirated from the implants. Significant portions of repair tissue exist in conditions of extremely low oxygen tension. Probably because all added oxygen is readily consumed, the wound fluid PO(2) increased only slightly in hyperoxic environment. The wound PCO(2) increased in parallel with the inspired PO(2), probably due to enhanced production of carbon dioxide. Hyperoxia shifted the wound metabolism from anaerobic towards aerobic glycolysis. This occurred concurrently with activation of citric acid cycle. Succinic dehydrogenase, a linking enzyme between citric acid cycle and electron transfer chain, also increased with increasing oxygen tension. This oxygen-induced metabolical change has been previously observed in many other tissues.