Fig. 30.   Curve showing the rate at which hypochlorite of sodium is destroyed in contact with living tissues.

Fig. 30. - Curve showing the rate at which hypochlorite of sodium is destroyed in contact with living tissues.

A 0.4 per cent. solution placed in an almost aseptic wound was reduced to 0.24 per cent. at the end of 2 minutes, and 0.16 per cent. at the end of 9 minutes.

The decrease in the strength of the solution of hypochlorite occurs at a variable rate, according to the nature of the tissues, the volume of the secretions, the form of the wound, and many other conditions, which do not permit us to forecast, in the case of a given wound, what will be the rate of destruction of the bactericidal substance. But these experiments show that the tissues exert a manifest action upon the hypochlorite, that the strength of the solution is rapidly modified, and that in order to maintain it at a constant figure fresh quantities must incessantly be supplied to the wound. Hence the necessity of a large quantity of antiseptic solution if we wish to sterilise a wound.

6. Mode of Action of Hypochlorite. - Dakin attributes the bactericidal action of the hypochlorites to a chemical reaction similar to that which takes place between ammonia and a hypochlorite, and results in the simplest of the chloramines, as Raschig demonstrated long ago. The destruction of micro-organisms by an antiseptic is due probably to chemical modifications produced in the substances constituting living cells, either by the direct action of the antiseptic, or by the action of products resulting from the combination of the antiseptic with the substances in the midst of which the micro-organisms are found. Amongst the substances contained in living cells and capable of reacting with hypochlorites, proteins play probably the chief role. The action of hypochlorites on proteid matters consists, at least in part, in the substitution of chlorine for hydrogen in some of the NH groups, and, afterwards, in the formation of substances belonging to the group of chloramines. Dakin1 believes that the property possessed by hypochlorites of attacking proteid matters, forming compounds in which the halogen element is directly attached to the nitrogen, is closely bound up with their bactericidal action.

This hypothesis is supported by the following observations. Free chlorine, bromine, and iodine vary only slightly in their germicidal power. But if the halogen element is converted into the hypochlorite or the hypo-bromite, a strongly marked difference appears. The bactericidal action of hypochlorites on staphylococci suspended in water, is almost equal to that of free chlorine, whilst that of hypobromites is only equivalent to about one-hundredth of that of free bromine. The bactericidal action of hypoiodite is almost nil. The insignificant bactericidal power of hypobromites and hypoiodites coincides with their feeble capacity for reaction with proteins and amino-acids.

It is also interesting to consider why hypochlorites, which destroy the skin in vitro, leave unharmed living tissues and do not interfere with the healing of wounds.

Soda, it is well known, produces immediate dissolution of the tissues. Fiessinger's experiments, upon the rapidity of dissolution of leucocytes, confirms the fact that the solvent action of the hyposulphites is a function of their soda content. Fiessinger also ascertained that this action diminishes according as hypochlorites containing quantities greater or less of soda are used.

1 Dakin, Cohen, Daufresne, and Kenyon, Proceedings of the Royal Society, 1916.

Daufresne's experiments, which we have already quoted, demonstrate plainly that Labarraque's solution, which contains free alkali, causes dissolution of skin at a moment when Dakin's solution has not yet produced any perceptible lesion.

Tissues provided with a normal circulation resist perfectly the action of Dakin's solution under the conditions of our experiments. Guillaumin and Vienne attribute 1 this resistance to the following phenomenon. Take an alkaline solution of such concentration that it hydrolyses and dissolves the fragment of tissue placed in it. If a certain quantity of neutral salt be added, it is known that the tissue can be immersed in the solution thus modified, without its structure becoming altered. Guillaumin and Vienne made the following experiment. Fragments of skin were placed in a 3 per cent. solution of soda, to which had been added 12 per cent. sodium chloride. Other portions of skin were placed in a 3 per cent. solution of soda to serve as controls. The skin immersed in the solution containing chloride remained intact, while the control fragments swelled up and became transparent. However, analysis showed that the same quantity of alkali had been absorbed by the skin in each case. This important process is known in tanneries as "pickling." Guillaumin and Vienne consider it the reason why tissues are not injured by hypochlorite.

Whatever may be the explanation of the resistance of living tissues to hypochlorite, this phenomenon provides a working hypothesis for the chemiotherapy of wounds in spite of the destructive action of hypochlorite on proteins.

1 Guillaumin et Vienne, Archives de Medecine et de Pharmacie militaire, 1916.