the effect of abdominal wounding on the rate of tissue regeneration
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66 Specialia EXPERIENTIA 26/1
Ansteigen der Werte um etwa 10% infolge des Holmes- Effektes, w iees bei einer Schnittdicke yon 20 ~z fiir zyl indrische Objekte vom Durchmesser der Plazentar- zotten (50-80 V) zu erwarten w/ire, wird damit wieder kompensiert und kommt im Messergebnis nicht zum Aus- druck. Entsprechende t)berlegungen gelten auch fiir die Messung der OberflS, che.
Summary. In stereological measurings of volume and surface of human placental villi systematic over- est imation due to section thickness (Holmes-effect) was
not observed, probably because it is compensated by overlapping of sections of villi.
R. BAUR 5 A bteilung Anatomic der Rhein.- West/. Technischen Hoshschule, Aachen, 51 Aachen (Deutschland), 1. Oktober 1969.
s Arbeit mit Unterstiitzung durch die Deutsche Forschungsgemein- schaft.
The Ef fect of Abdomina l Wound ing on the Rate of
I t has been demonstrated that the rate of tissue regeneration is higher in male rabbits than it is in females 1 and it has been proposed that the higher androgen level in males is concerned in producing this effect ~. The reduct ion of the androgen level in males by orchidectomy does 'not cause a simple lowering of their regeneration rate as might be expected. Instead a signif icant reduct ion in regeneration rate only occurs if there is a considerable delay between castrat ion and the excision of ear tissue. Where castrat ion is followed by immediate excision of ear tissue the amount of regenerative growth achieved by 49 days after excision (when measurements ceased) is similar to that found in control males. In all the groups of castrated males there is an initial acceleration of growth, inversely proport ional to the delay between castrat ion and the excision of ear tissue, followed by a reduction in the rate of regeneration a. One possible ex- p lanat ion for the initial increase is that the stress pro- duced by the castrat ion procedure temporar i ly st imulates regeneration so that the predicted inhibitory effect of decreased testicular androgen supply is masked. The present communicat ion describes some exper iments per- formed to investigate this possibil ity.
Method. Under i.v. pentobarb i tone anaesthesia a mid- line abdominal incision, 3 cm long and ending 3 cm above the symphysis pubis, through the whole thickness of the abdominal wall, was made in each of a series of rabbits, of
Tissue Regenerat ion
mixed stock and over 6 months old. The wound was sutured in 2 layers, one for the per i toneum and muscle and one for the skin, wi th continuous sutures of silk. In one group of males and one of females, 1 cm ~ of tissue was excised through the full thickness of the pinna of the ears immediately after abdominal wounding. In a further 2 groups of rabbits the ear tissue was excised 14 days after the abdominal operation. Wounds were made in both ears of each rabbit but the growth of the regenerate ~ was only measured, by a photographic procedure, in one. The growth of the ear regenerates of the 4 groups of ab- dominal ly wounded animals was compared with that of a series of controls wi thout abdominal wounds.
Results and discussion. The effect of abdominal wound- ing on the growth of the ear b lastemata is shown in Figures 1 and 2 and Tables I and II . The presence of an abdominal wound st imulated regeneration, for there was signif icantly more growth in the ear regenerates of all 4 groups of abdominal ly wounded rabbits by 14 days after ear tissue excision than there was in their respective controls (P < 0.005 in all cases). In females the regenera- t ion rate was mainta ined at a high level so that at 49 days,
1 J. JOSEPH and M. DYSON, Nature 208, 599 (1965). 2 j. JOSEPH and M. DvSON, Br. J. Surg. 53, 372 (1966).
M. DYsoN and J. JosEpH, J. Anat. 103, 491 (1968).
07 v Zl Z8 35 4Z ~9
Fig. 1. The effect of abdominal wounding on the rate of regeneration of ear tissue in males. A, Abdominal wound made at the time of ear tissue excision; [~, abdominal wound made 14 days before ear tissue excision; D, control males without abdominal wounds.
Fig. 2. The effect of abdominal wounding on the rate of regeneration of ear tissue in females. Ik, Abdominal wound made at the time of ear tissue excision; It, abdominal wound made 14 days before ear tissue excision; 0, control females without abdominal wounds.
15.1. 1970 Specialia 67
when the las t measurements were made, the mean areas of the ear regenerates in both abdomina l ly operated groups were s ign i f i cant ly h igher than the cont ro l s (_P < 0.010 in both cases). In ma les the growth ra te fell
Table I. Effect of abdoufinal wounding on regenerative growth in males
Group Treatment Days N Mean area of Standard after regenerate error of excision as%of mean
1 Abdominal wound 14 5 50.7 4- 5.3 made at the time of 21 5 66.4 4-t-6.1 ear tissue excision 28 5 70.3 4-4.3
35 5 78.6 42 5 79.2 4-5.9 49 5 88.3
2 Abdominal wound 14 6 50.5 4-3.7 made 14 days before 21 6 61.7 4-5.4 ear tissue excision 28 6 71.6 4-6.3
35 6 77.8 4-6.6 42 6 81.1 4-6.9 49 6 86.8 4-6.0
3 Control males with- 14 18 22.3 4-3.5 out abdominal 21 18 49.1 4-2.4 wounds 28 18 63.9 4-2.8
35 18 72.8 =t=2.6 42 18 77.0 4-2.8 49 18 85.2 4-2.6
Table II. Effect of abdominal wounding on regenerative growth in females
Group Treatment Days N Mean area of Standard after regenerate error of excision as % of mean
4 Abdominal wound 14 8 48.7 4-2.7 made at the time of 21 8 61.2 z~3.5 ear tissue excision 28 7 75.9
35 8 88.0 4-4.2 42 7 91.0 4-3.5 49 7 97.6
5 Abdominal wound 14 6 44.1 =t=2.9 made 14 days before 21 6 67.2 +4.4 ear tissue excision 28 6 72.4 i2 .9
35 6 78.9 42 6 88.5 49 6 89.6 4-3.8
6 Control females 14 11 21.6 i4 .1 without abdominal 21 11 38.9 wounds 28 12 45.3 4-5.6
35 12 57.1 4-5.6 42 12 63.2 i5 .5 49 12 67.2 4-4.9
progress ive ly a f te r the in i t ia l acce lerat ion. I t wou ld thus appear that surgery can a f fect the regenerat ion ra te a t a d i s tant site, and that the ef fect is g reater and las ts longer in females than in males .
The mechan ism by wh ich operat ive procedures a f fec t d i s tant regenerat ion has not been es tab l i shed . A l though the poss ib le re lease of a wound hormone f rom the ab- domina l wounds cannot be d i scounted , it may be that changes in the hormona l env i ronment in response to s t ress are concerned . Such changes do occur 4,5, par t i cu - la r ly in response to surg ica l s t ress ~. S ince the hormona l env i ronments of ma les and females are d i f ferent , it cou ld also account for the d i f fe rent responses in g rowth ra te found in ma les and females towards the end of the regenerat ive process . P rov ided that the nerve supp ly to the in ju red par t is in tac t 7 there is a p i tu i ta ry -adreno- cor t i ca l response to surg ica l s t ress resu l t ing in an in- c reased level of ACTH in the b lood and an inc reased output of g lucocor t i cos tero ids s. The la t te r may he lp to in i t ia te the regenerat ive process by in tens i fy ing pro te in metabo l i sm and mak ing amino ac ids and nuc leoprote in ava i lab le for use in the later , anabol ic , phase of repair . S ince ACTH s t imu la tes adrena l androgen product ion s and many androgens are anabo l i c agents , these may also s t imu la te regenerat ion . I t has been demonst ra ted that the adrena l g lands are larger, and the p lasma concent ra t ions of adrena l hormones h igher , in female ra ts than in ma les 18. Th is may exp la in , if it is also t rue for rabb i t s , why the s t imu la t ion of regenerat ive ra te was greater in females a f te r surg ica l s t ress than in males , and why it pers i s ted longer in females n,12.
Zusammen/assung. Verwundung induz ie r t Regenerat ion in ent fe rnten Ste l len bei m/ inn l i chen und we ib l i chen Kan inchen . Dies gi l t ffir f r i ihe Regenerat ionss tad ien bei m/ inn l i chen T ieren, w~hrend bei We ibchen die Regenera - t ionswi rkung mindestens 49 Tage anhAlt . Es w i rd ver- mutet , dass es s ich um hormona le E inwi rkungen in fo lge St ress hande l t .
J. JosEPH and MARY DYSON Anatomy Department, Guy's Hospital Medical School, London, SEJ (England), 14 July J969.
4 H. SELYE, Stress (Acta Inc., Montreal 1950). H. SELYE, Science 122, 625 (1955).
@ L. P. LE QUESNE, CIBA Foundation Study Group 27, 29 (1967). 7 D. M. HUME and R. H. EGDAHL, Ann. Surg. 150, 697 (1959). 8 C. E. COOPER and D. H. NELSON, J. elin. Invest. 4/, 1599 (1962). t) A. PRADER, CIBA Foundation Study Group 27, 29 (1967).
10 E. SAKIZ, C. r. hebd. S~anc. Acad. Sci. Paris 251, 2237 (1960). 11 This work was supported by a grant from the Medical Research
Council, London. 12 The authors wish to thank Miss MARY TYDD for technical assistance
during this investigation.
Lymphostatic Retinal Haemangiopathy
A pre lymphat ic - lymphat ic pathway has been de- scr ibed in the wal l of cerebra l b lood vessels , l ead ing pro- te in and t i ssue f lu id to the cerv ica l l ymphat ics . B lockage of th i s sys tem resu l t s in oedematous a l te ra t ions in cerebra l b lood vesse ls ; the te rm 'Lymphostat i c Cerebra l Haemang iopathy ' was co ined f