CICATRIZATION OF WOUNDS. IX. INFLUENCE ON THE HEALING ~]0 WOUNDS OF VARIATIONS IN THE OSMOTIC TENSION ~]O THE DP~ESSINO. YB M.D., P. ALEXIS CARREL, ETMOCEL DU ,YJtON )mA ANNE .LERRAC (From eht Laboratories of The Institute Rockefeller for Medical Researck, New York, and Hospital 21, France.) Compikgne, Do w n lo for publication, March (Received ,22 ).7191 ad e d fro m In previous articles it has been shown that the curve representing h ttp the process of dcatrization of an aseptic wound is geometric, t, ' ://ru and can be calculated by the formula of du Notiy. The compari- pre son of the calculated and observed curves alters the study of the ss.o rg effect upon cicatrization of a substance applied to the surface of the /jem /a wound. If the daily decrease of the area of a wound is known, and rticle if the wound is maintained in a condition of surgical asepsis, the -p d modifications in the rate of the healing process can be attributed to f/26 /2 the special action of the substance applied, and the extent of this /27 9 /1 action can be accurately measured. 1 7 4 Up to the present it has not been known to what degree the rate 48 1 /2 of cicatrization of a wound can be affected by the dressing. Surgeons 79 .p have studied the influence of so called healing substances when df b applied to wounds, but no precise conclusion has resulted from these y gu e observations. No method existed of measuring exactly the surface st o n of a wound and of calculating with any degree of accuracy the rate 06 Ja of the healing process. On the other hand, the bacteriological con- nu a dition of the wounds experimented upon was never taken into con- ry 2 0 2 sideration. Such modifications of the rate of healing as were noticed 3 might be equally attributable to the action of the substance employed upon the bacteria of the wound as to the tissues themselves. Carrel, 1 ,.A and Hartmann, A., J. Exp. Mad., ,6191 xxlv, .924 du Noiiy, P. L., J. Exp. Mad., ,6191 xxiv, .154 972 280 CICATP, XZATION OF WOUNDS. IX The following experiments were undertaken to ascertain whether modifications in the osmotic tension of the dressing exert an influ- ence on the rate of repair. EXPEI~.IMENTAL. Surface wounds already covered with granulating tissue were selected. The normal rate of cicatrization of the wound was first obtained by sterilization with Dakin's hypochlorite solution or Daufresne's chloramine paste. The experiment was started as soon D as the regular progress of the observed curve, as compared with the ow n curve calculated' according to du Noiiy's formula, was established. loa d e The measurements of the wound and the plotting of the curve were d fro made according to the technique previously described. Distilled m h water or hypertonic solution was applied to the surface of the wound ttp://ru by means of small perforated rubber tubes bound at the extremities pre and enveloped by a small cylindrical pad of Turkish toweling. The ss.o rg length of the pad varied from 4 to 8 era., according to the size of the /je m woovuenrd . the Fowuourn d threads and were placed attached transversely to the acrosss kin by the means pad extenodf ed small /article-p d adhesive patches in such a manner as to keep the flushing tube in a f/26 /2 fixed position over the granulations. The sterile liquid was contained /27 9 in a flask placed about 1 meter above the patient's mattress, and /11 7 4 reached the flushing tube by means of a Murphy drop tube. As a 48 1 /2 rule, in these experiments about 125 gin. of fluid flowed out per hour. 7 9 .p Another technique was also used to bring into contact the surface df b of the wound and the distilled water or hypertonic solution. Agar y g u e cakes containing distilled water or hypertonic sodium chloride solu- st o n tion were applied to the surface of the wound. These constantly 06 gave up their fluid contents, and were left at the surface of the wound, Jan u a according to the nature of the experiment, from 6 to 21 hours and even ry 2 0 24 hours per day. In order to prevent immediate reinfection, the 23 wound was flushed from four to six times in 24 hours with Dakin's solution. Another method consisted in applying for several" hours every day a dressing corhposed of sodium stearate and chloramine paste. Chloramine paste, 01 parts per 1,000 was generally used, because reinfection takes place under 4 parts per 1,000. The wound ALEXIS CARREL, .P .L IID NOUY, AND ANNE CARREL 281 was examined bacteriologically every day. As soon as reinfection occurred the experiment was interrupted and the wound thoroughly sterilized. Every 4 days the surface of the wound was measured and the curve was plotted and compared with the calculated curve. The patients were kept in bed during the experiment and were under the supervision of a nurse day and night. Influence of Distilled Water on the Rate of Healing of a Sterile Wound. In the following experiments the wounds were flushed with dis- tilled water from 2 to 4 hours every day. D o w n lo a d e d fro m h ttp ://ru p re ss.o rg /je m /a rticle -p d f/2 6 /2 /2 7 9 /1 1 7 4 4 8 1 /2 7 9 .p d f b y g u e st o n 0 6 Ja n u a ry 2 0 2 3 282 CICATRIZATION O1 ~ WOUNDS. IX g/tea k ~0~ \\ I \\ 1J 10 \ D k ow n lo a 4, " de d fro 1 m h .:PoVv9 /7 21 25 Dc~3 7 H ~ ttp://rup re observed curve. ss.o - - calculated curve. rg /je Cicatrization curve. m/a rticle ~OY. -pd f/2 6 80 /2 /2 7 9 /1 G0 17 ! ,I[ 44 8 1 /2 7 9 .p d f b y g u e st o n 0 6 Ja " / nu b ary 2 0 1 ! 23 . 1 Bacteriological curve. TExT-FIG. 1. Experiment 1. Case 646. ALEXIS )LER~,PAC P. L. DU NOOY~ AND ANNE CARREL 283 Experiment I (Text-fig. /).--Case 646, age 25 years. Nov. 17, 1916. Sterile wound in the calf, 21 sq. era. in area. The wound is surgically aseptic. Flushing with distilled water for 2 hours. Then flushing with 30 per cent hypertonic solution for 2 hours. The dressing was kept in place until the following morning. Nov. 18. The appearance of the wound has not changed. Surface area 12.1 sq. era. 30 to 50 bacteria per field. Same dressing. Flushing with distilled water for 2 hours. Flushing with a hypertonic solution for 2 hours. Nov. 19. The appearance of the wound l~s remained the same. Surface area 12.6 sq. cm. 50 to 100 bacteria per field. Dressing with chloramine paste, 10 parts per 1,000. Nov. 20. Same dressing. Surface area 11.1 sq. era. D o Nov. 21. Chloramine dressing, 4 parts per 1,000. Surface area 10.5 sq. cm. wn lo 4 bacteria per field. ad e Nov. 22. Flushing with distilled water for 4 hours. Chloramine dressing, d fro 4 parts per 1,000 for 20 hours, m h Nov. 23. Granulations smaller. Surface area 9.2 sq. era. Flushing with ttp distilled water for 4 hours. Chloramine dressing, 4 parts per 1,000. ://ru p field. Nov. Numerous2 4. Same cocci. appearance. Flushing Surface with distilleda rea 8.4 water sq. era. for 8 18 hours. to 20 bactCehrlioara mlne per ress.org dressing, 10 parts per 1,000. /jem Nov. 25. 1 bacterium in 51 fields. /article -p d f/2 6 /2 /2 7 9 /1 1 7 4 4 8 1 /2 7 9 .p d f b y g u e st o n 0 6 Ja n u a ry 2 0 2 3 284 CICATRIZATION OF WOUNDS. IX \ 4a 40 \ 3a \ ~o za \ 20 9,1 1o D o w n lo a d e d 1~ 17 21 29 ~ 7 11 15 ~_I fro ..YoVo .Dee. m h Cicatrization curve. ttp://ru p re ss.o rg /je V dVO m /a 80 I )m~ rticle -p d f/2 60 6 ! /2 /2 7 9 ~ O4 \ 1 /1174 4 8 \ 1 20 /27 T f 9.p \ / df by g u \ / est o n 0 6 Ja 1 n ~Y ua J__-y,~~ l \ / ry 2 k / 02 3 Bacteriological curve. TExT-FIG. 2. Experiment 2. Case 694. ALEXIS CARREL, .P .L DU NOTJY, AND ANNE CARREL 285 Experiment 2 (Text-fig. 2).--Case 694, age 20 years. Sterile wound 33.3 sq. cm. in area. Nov. 17, 1916. Flushing with distilled water for 2 hours, followed by 2 hours' flushing with 30 per cent hypertonic sodium chloride solution. The dressing was not renewed until the following morning. Nov. .81 The wound appears the same. Surface area 30.4 sq. cm. 20 to 30 bacteria per field. Flushing. with distilled water for 2 hours and hypertonic solution for 2 hours. Nov. .91 Same appearance. Owing to the infection, the rate of cicatrization has diminished. The surface area is 29.6 sq. cm. 55 bacteria per field. Chlora- mine dressing, 01 parts per 1,000. Nov. 20. Same appearance. The curve has caught up with the normal curve. D o Surface area 26 sq. era. 20 bacteria per field. Chloramine paste, 01 parts per wn lo 1,000. a d e Nov. 21. Same appearance. Surface area 23.6 sq. era. 4 bacteria per field. d fro Chloramine dressing, 4 parts per 1,000. m h Nov. 22. Chloramine dressing, 4 parts per 1,000. 1 bactl~rium per 8 or 10 ttp fields. ://ru p and Nov. the e23. xperiment Same trweiatthm ent. distilled Surface water alone area ca1n7 .3 be sq. resumed. cm. The wound is sterile ress.org Nov. 24. Flushing with distilled water for 8 hours. Dressing with chloramine /jem paste, Nov. 4 p25. arts Fluspheirn g 1,000. with ' 1 badcitsteirlileudm water in 01 for to 8 51 hours. fields. /article-p Nov. 26. Flushing with distilled water for 24 hours. In order to keep the df/2 6 wound sterile, an injection of Dakin's solution is made every 6 hours. Surface /2 /2 area 14.6 sq. cm.; calculated area 41 sq. cm. 1 bacterium per field. 79 /1 Nov. 27. Flushing with distilled water for 24 hours. 1 bacterium in 3 fields. 17 4 Nov. 28. Flushing with distilled water for 24 hours. Observed area 21 sq. 48 1 era. No apparent change, Calculated area 11.8 sq. cm. 10 to 51 bacteria per /27 9 field. .pd Nov. 29. Flushing with distilled water for 24 hours. f by g Nov. 30. Retardation of the healing process. Observed area 11 sq. cm.; ue calculated area 9 sq. cm. 51 to 20 bacteria per field. Flushing with distilled st o n water for 24 hours. 06 Dec. .1 Experiment interrupted on account of infection. Application of Jan u a compresses soaked in Dakin's solution; renewed six times in 24 hours. ry 2 Dec. 2. S~me dressing. Inriumerable small bacilli. 02 3 286 CICATRIZATION OF WOUNDS. IX Jie~ 8 N 7 6 5 4 J 2 D o w n lo a 2/ 2~ 20 de d ~Vov, fro m Cicatrization curve. h ttp ://ru p re ss.o NO./( rg/je ~J 23 ~5 £7 m /a rticle -p d f/2 6 /2 /2 7 9 /1 i 17 4 4 8 1 /2 7 9 .p d f b / y gu e st o n 0 6 Ja n u /A~. / ary 2 "~..~ ~J 02 3 curve. Bacteriological .GIF-TxET .3 Experiment .3 Case .496 ALEXIS CARREL~ .P .L DU NOOY, AND ANNE CARREL 287 Experiment 3 .gif-txeT( 3).--Case 694, age 20 years. Nov. 21, 1916. Sterile wound of the wrist, measuring 1.8 sq. cm. Since Nov. 31 the process of repair has been regular. Flushing with distilled water for 2 hours, followed as in the previous experiment by application of chloramine paste, 4 parts per 1,000, in order to prevent infection. Nov. 22. Flushing with distilled water for 4 hours, followed by chloramine dressing. Observed surface 5.1 sq. cm.; calculated surface 1.8 sq. cm. 1 bac- terium in 4 fields. Nov. 23. Flushing with distilled water for 6 hours. Dressing with chloramine paste. Nov. 24. Flushing with distilled water for 8 hours. Dressing with chloramine paste. 1 bacterium in 51 to 20 fields. D o Nov. 25. Scale formed on the wound. Dry dressing. w n Nov. 26. Scale is removed. Area of the wound is 0.37 sq. cm.; calculated loa d e surface 0.7 sq. cm. 51 to 20 bacteria per field. Dressing with chloramine paste. d fro m h Influence of Hypertonic Sodium Chloride Solution on the Rate of Healing ttp of a Sterile Wound. ://rup re ss.o In the following experiments the wounds were flushed with hyper- rg /je touic sodium chloride solutiou. m /a rticle -p d f/2 6 /2 /2 7 9 /1 1 7 4 4 8 1 /2 7 9 .p d f b y g u e st o n 0 6 Ja n u a ry 2 0 2 3 288 CICATRIZATION OF WOUNDS. IX *(cid:127)t CZm. dO O7 6O ~0 0 5O 2O D 10 ow n lo a d '~ 50 4, ~ }~ 2.1 16 2.0 ~4 28 1 5 0 IJ, 172I 25 9.2 2 6 I0 ~1 16 ed ..v Dec. J,~o. Feb. fro m Cicatrization curve. http ://ru p re ss.o rg .CED JAN /je m 2 4 6 810 141618)-022. 26 30 7 /a 80 rticle -p d 60 f/2 6 /2 /2 o~ 40 79/1 1 7 4 4 8 1 /2 7 9 .p d t/'x f by g u i est o n 0 6 Ja n : /I ' " ua ry 2 0 2 3 Bacteriological curve. TExT-FIG. 4. Experiment 4. Case 639.
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