Other substances - for example, Browning's flavine-exert a direct action on the process of cicatrisation, as is shown by the curves of cicatrisation and sterilisation. In the case of a patient whose wound was sterile, and undergoing cicatrisation in a normal manner, installations of flavine were twice applied, the solution being 1 in 1000 on the first occasion and 1 in 5000 on the second.
Fig. 25. - Sterilisation curve of the foregoing wound.
The wound remains aseptic during the first application of flavine. The retardation of cicatrisation observed is due to the peculiar action of flavine upon the wound.
Fig. 26. - Cicatrisation'curve of a wound treated with Dakin's solution. The observed curve coincidesr throughout with the calculated curve. The observed curve is the unbroken line; the calculated curve, the dotted line.
Immediately the curve became horizontal and even proceeded to rise, for cicatrisation was not only arrested; it actually retrogressed, and the dimensions of the wound increased (Fig. 24). At the same time the bacterial curve showed that the wound had remained aseptic (Fig 25). It was therefore obvious that the retrogression of cicatrisation, not being due to infection, was to be attributed to a deleterious action of the substance itself.
When we compare the curves of wounds treated with the aforesaid substances with the curves of wounds treated with hypocholorite or chloramine, we notice an obvious difference. The wounds treated with hypochlorite (Figs. 26 and 27) or with chloramine (Figs. 28 and 29) become cicatrised according to the cicatrisation curve calculated by du Nouy's formula, with the normal rapidity of aseptic wounds.
In short, in the healing of an infected wound the acceleration produced by hypochlorite is due to its antiseptic power. Hypochlorite does not appear to have any marked action on the tissues in the direction of cicatrisation, when it is used under the conditions of our experiments. Probably it has a slightly retarding effect on the healing of aseptic wounds. But in practice this influence is negligible.
Fig. 27. - Sterilisation curve of the foregoing wound. The wound remains sterile throughout the treatment.
Dakin's solution, therefore, we may conclude, when applied under suitable conditions, does not in any appreciable manner, harm tissues under repair, which is contrary to the belief of most surgeons.
Fig. 28. - Cicatrisation curve of a wound dressed with chloramine (case No* 706). The observed curve coincides exactly with the calculated curve.
Fig. 29. - Sterilisation curve of a wound treated with chloramine. The wound remains constantly sterile.
5. Action of the Tissues on Hypochlorite of Soda. - The dead or living tissues exert a marked action on the concentration of a solution of hypochlorite. In M. Daufresne's experiment, which we have already described, wherein fragments of skin were placed in an excess of Dakin's hypochlorite, it was found, after the lapse of some twenty-four hours, that the concentration of the solution was very greatly diminished. In the experiments conducted by Carrel on wounds of the brain after the death of the animal, it was found that hypochlorite of soda decomposed with very great rapidity. The wound was filled with a solution containing 0.5 per 100 of hypochlorite. At the end of six minutes the solution was withdrawn, and the degree of concentration was found to be only 0.16 per 100. A fresh portion of solution was injected, and withdrawn at the end of seven minutes; its degree of concentration was still 0.23 per 100. But if a third portion of Dakin's solution was injected into the same cavity, it was found that the degree of concentration had not diminished by more than half at the end of eight minutes. Similar experiments made upon other tissues show that the concentration of a solution of hypochlorite may diminish by 70 per 100 in five minutes.
This destruction of hypochlorite is still more active when the solution is in contact with living tissues. Experiments were made in the peritoneum of the cat or rabbit. A portion of Dakin's solution containing 0.45 per 100 of hypochlorite was poured into a small cup which contained a portion of the epiploon of a cat, which was provided with its normal circulation. At the end of seven minutes the strength of the solution was only 0.07 per 100. A large number of analogous experiments were carried out, and from these it was possible to prove that hypochlorite loses, in a few minutes, when in contact with tissues equipped with their normal circulation, more than four-fifths of its strength. Similar experiments were conducted with wounds in course of cicatrisation. Deep wounds were selected for the purpose, so that the solution could lie in them readily. The wounds whose action on hypochlorite was studied were completely aseptic, or still contained a few microbes. The hypochlorite, whose degree of concentration was known, was poured into the wound, and at intervals of two minutes a few cubic centimetres of the liquid were withdrawn and immediately analysed. The results of the experiments were expressed in the form of a curve. In aseptic fractures of the tibia, or fractures which were almost completely aseptic, the strength of the hypochlorite as a rule decreased from 0.4 to 0.15 in six minutes. At the end of half an hour only 0.05 to 006 of hypochlorite was left. In Fig. 30 the curve shows the progressive disappearance of hypochlorite from a solution poured into a wound accompanying a fracture of the tibia. The solution, which was 0.40 per 100 at the outset, was 0.27 per 100 two minutes later, and 0.16 per 100 at the end of four minutes. When six minutes had elapsed the strength was reduced to 0.13 per 100.