Local hyperalimentation of experimental granulation tissue.

The effect of local hyperalimentation on developing granulation tissue was studied in rats. Cylindrical hollow viscose cellulose sponge implants were used subcutaneously as an inductive matrix fro the growth of granulation tissue. In the first, control group the implants were kept untouched while the second, "sham" group was treated daily by withdrawing 1 ml of wound fluid from the central dead space of the implant and then injecting the fluid back. In the third, hyperalimentation group the aspirated wound fluid was substituted with a corresponding volume of sterile, nonpyrogenic solution containing a mixture of amino acids (Le-7402 A) and glucose, electrolytes and vitamins (Le-7402 B). Within the first week of tissue growth daily application of these nutritional substances caused a changeover of local tissue from predominantly anaerobic towards more oxidative metabolism. Measurement of nucleic acid and hydroxyproline contents indicated enhanced accumulation of cells and collagen in tissues receiving local hyperalimentation. The results combined with earlier data from our laboratory strongly suggest that several types of wounds, especially those containing a marked dead space or large regenerative area, exist in chronic lack of oxygen and other nutrients. Therefore, the healing process in these wounds can be stimulated, to a certain extent, by exposure to increased oxygen tension and/or by local hyperalimentation.

Oxygen tensions in healing anastomosis of rabbit aorta.

Tissue oxygen tensions in healing anastomoses of rabbit abdominal aortas were measured with ultramicro-oxygen cathodes with 1 to 3 mum tips. Two days after constructing the anastomosis, the over-all profile of intramural oxygen tension was different markedly from that of normal aortic wall, showing a progressive fall of Po2 from adventitia to media and no increasing gradient from media to intima. One week after operation to intimal Po2 increased and the oxygen gradient due to diffusion from the lumen was re-established. By the end of the second week adventitial and medial oxygen tensions reached their minimum. Six weeks after operation the oxygen tensions in the anastomosis resembled those of an intact aortic wall, suggesting that the availability of oxygen to the injured area had been re-established fully.

Energy metabolism of experimental wounds at various oxygen environments.

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.

Tissue oxygen and carbon dioxide tensions in healing rabbit tibias.

Tissue gas tensions were measured in healing rabbit tibias by means of an implanted Silastic tonometer. During the course of the healing, tissue oxygen tensions increased progressively and carbon dioxide tensions underwent a gradual decline. In all phases of repair, bone tissue gases responded to systemic hyperoxia and hypercarbia. Occlusion of local circulation resulted in tissue anoxia and accumulation of carbon dioxide. Acetazolamide, an inhibitor of carbonic anhydrase, elevated the carbon dioxide tension in the bone but not in the blood which supports earlier data indicating the presence of a functional carbonic anhydrase system in actively metabolizing bone tissue.

Effects of hyperbaric oxygenation and prolonged hypoxia on the healing of open wounds.

In a study on rats, long-tern intermittent hyperbaric oxygenation at 2 ATA had no effect on the healing rate of open wounds in which the circulation was left intact. When the wound edges were devascularized, however, hyperbaric oxygen enhanced the wound closure rate in the final stages of healing, thus counteracting the delay caused by disturbed blood supply. During the hyperbaric exposure, tissue pO-2 increased considerably in both normal and devascularized skin, whereas tissue pCO-2 increased only slightly. Combined systemic and local hypoxia--12% oxygen at 1 atm--retarded the closure rate of full-thickness skin wounds. This was noted both in acclimatized and in unacclimatized rats. Thirteen-day adaptation to hypoxia increased the healing rate and subcutaneous tissue pO-2 to normal levels, but when hypoxia was continued, tissue pO-2 and the wound closure rate decreased markedly. This was probably due to a decreased blood flow induced by secondary erythrocytosis and an elevated blood viscosity.

Oxygen and carbon dioxide tensions in healing tissue.

Oxygen and carbon dioxide tensions were studied in experimental granulation tissue growing into a thin sheet of cellulose sponge. Both the base-line PO2 and the response in oxygen tension to pure O2-breathing were highest in 7-day-old implants, displaying a slight decrease as the healing progressed. Lower tissue carbon dioxide tensions and oxygen consumption rates were noticed also in older implants. The oxygen tension gradient between the wound fluid and the edge of the granulation tissue in cylindrical cellulose sponge implants decreased as the healing progressed.

Effect of changes in inspired oxygen tension on wound metabolism.

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.