Max Taffel

Effect of Absolute and Partial Vitamin C Deficiency on Healing of Wounds.

It is now well established that the intercellular substances in general, and the collagen of all fibrous tissue structures in particular require ascorbic acid for their production and maintenance. Aschoff and Koch 1 made thorough postmortem studies of World War soldiers who had died of scurvy, and demonstrated constant pathological changes in the supporting tissues of the body. Höjer 2 found a general atrophy of the connective tissue in scorbutic guinea pigs, and pointed out for the first time a general deficiency in the formation of collagen. In a series of more recent communications Wolbach 3 4 5 and his collaborators confirmed the observations of Höjer, and conclusively showed that ascorbic acid is intimately concerned with the synthesis and maintenance of intercellular supporting materials. Jeney and Törö, 6 when they added ascorbic acid to the nutrient medium of a culture of fibroblasts in vitro, found a marked increase in the number of collagen fibrils that were produced. Since the repair and tensile strength of soft tissue wounds are direct functions of fibroblastic proliferation and collagen formation, it is at once apparent that Vitamin C may play a prominent rôle in the phenomenon of wound healing. Saitta 7 reported a delayed healing of exposed surface wounds in guinea pigs that had been kept on a Vitamin C deficient diet for more than 15 days. On the other hand, when a Vitamin C containing extract was applied directly to the wound, the healing time was appreciably diminished, regardless of whether the animals were maintained on a normal or a scorbutic dietary regime. He determined the rate of healing by actual daily measurements of the length and breadth of the wound.

Effect of Sulfanilamide on Wound Healing.

Bricker and Graham 1 reported that sulfanilamide had an inhibitory effect upon the healing of stomach wounds in dogs. Their determinations were made on the 3rd, 5th and 7th postoperative days. In view of the widespread and growing use of sulfanilamide and its related compounds, it seemed important to repeat these studies and to carry the determinations through all the normal phases of healing. The experiments were performed on adult white rats weighing about 250 g. The tensile strength of the wound was used as an index of healing. In addition comparative histological studies were made of the wounds. I. Control Group—51 animals. This group was maintained throughout the duration of the experiment on a diet of Purina dog chow. On the 3rd day of the diet a longitudinal wound measuring about one cm in length was made under ether anesthesia through the anterior wall of the stomach at its cardiac end. The wound edges were immediately re-approximated in one layer with a running continuous Connell suture of No. 000 plain catgut which, as has been previously shown, loses its tensile strength well within the 4th day. The abdominal wall was closed with 2 layers of fine No. A silk. On each of the 4th, 6th, 8th, 10th, 12th and 14th postoperative days 5 to 8 animals were sacrificed, and the strength of the wounds immediately determined by distending the stomach with air and noting its bursting point. The details of this method were described by Harvey and Howes. 2 Inasmuch as it has been shown that for approximately 4 days after the injury the wound has only the strength contributed by the holding power of the sutures, no studies were made during this first phase of healing.

Effect of Local Application of Sulfanilamide upon Wound Healing.

The efficacy of the sulfonamides in the systemic treatment of certain types of infection has been definitely established. During the past few years several communications 1 , 2 , 3 , 4 , 5 , 6 have described and recommended the application of these drugs directly into raw wounds as a prophylactic or therapeutic measure against infection. Most of these reports based their contentions upon qualitative impressions gathered from the observation of a small series of patients rather than upon controlled studies. Before indiscriminately depositing these drugs into a raw wound it is essential to determine first of all whether they have any noxious effect upon the tissues involved in the healing of the wound. Bricker and Graham 7 reported that the systemic administration of sulfanilamide had an inhibitory effect upon the healing of stomach wounds in dogs during the first 7 postoperative days. Taffel and Harvey 8 found that sulfanilamide did not affect the healing of stomach wounds in rats during all of the normal phases of healing. The drug was given orally in doses sufficient to maintain an adequate and sustained “therapeutic” blood level. This series of experiments was carried out to determine the effect of the local application of sulfanilamide upon the healing of a soft tissue wound. Adult white rats weighing about 250 g were used. The tensile strength of the wound served as an index of healing. In addition, histological studies were made of the wounds. I. Experimental Group. 57 animals. This group was maintained throughout the duration of the experiment on a diet of Purina Dog Chow. On the 3rd day of the diet the stomach was delivered through an incision in the anterior abdominal wall and 0.2 cc of a 3% suspension of sulfanilamide in normal saline were injected through a fine needle into the wall of the cardia.

Effect of Sulphur-Amino Acid Deficiency on Wound Healing.∗

From the results of his numerous plant and animal experiments, Hammett 1 2 3 arrived at the conclusion that the sulphydryl radicle, naturally present in all cells, was the essential and universal stimulus to growth by increase in the number of cells. This hypothesis did not long remain unchallenged. Others, 4 5 after carrying out similar investigations, have either not been able to reproduce Hammetts results, or have preferred to lend to them another interpretation. Reimann 6 7 8 translated Hammetts work into the clinic and reported instances of chronic indolent ulcers which healed with dramatic swiftness following the direct application of sulphydryl compounds. He described a rapid proliferation of both the fibroblastic and epithelial elements of the wound. In recent years Rose 9 10 has demonstrated methionine and not cystine to be the indispensable sulphur-containing amino-acid. Cystine stimulated growth only in the presence of methionine. In the absence of the latter from the ration, however, the animals rapidly lost weight and died, even though an abundant amount of cystine had been supplied. The purpose of these experiments was to determine whether a deprivation of cystine and methionine in a degree sufficient to abruptly arrest growth, had any effect on the healing of soft tissue wounds. The tensile strength of the wound was used as an index of healing. Young growing rats weighing between 90 and 100 g were divided into 2 groups: (1) normal control, (2) sulphur-ammo-acid deficient. The experimental diet used was that described by Dyer and du Vigneaud, 11 and consisted of: This is a full diet, adequate in all the essential constituents except the sulphur-bearing amino-acids. It contains cystine and methionine sufficient only for the maintenance of the animal but not for normal growth and increase in weight.