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THE EFFECT OF INJECTION OF HYDROCORTISONE INTO RABBIT CALCANEAL

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THE EFFECT OF INJECTION OF HYDROCORTISONE INTO RABBIT CALCANEAL Powered By Docstoc
					THE

EFFECT

OF

INJECTION

OF

HYDROCORTISONE TENDONS
KUALA Pathology LUMPUR, of the MALAYA

INTO

RABBIT
P.
From the
BALASUBRAMANIAM

CALCANEAL
and K.
PRATHAP, and

Departments

of Orthopaedic

Surgery

University

of Malai’a

or for

Spontaneous local steroid rheumatoid

rupture therapy. arthritis, 1961,

of tendons has been reported in patients In most cases the patients were receiving systemic Smaill occurred lupus 1961, after erythematosus Melmed muscular 1965). activity or polyarteritis Most (Lee

receiving systemic nodosa tendon Ismail,

either steroid

systemic therapy and

(Cowan

Alexander 1961, Lee local steroid infiltration

of the 1957;

ruptures after Balakrishnan plays evidence of steroid to

and Rajakumar 1969; Bedi and Ellis 1970). It at least some part in the tendon rupture (Sweetnam to support this. The present study was undertaken into their the tendons rupture. of rabbits produces any damage

seems certain that 1969) but there to find out whether to the tendons

hydrocortisone is no direct infiltration may

which

contribute

MATERIALS

AND

METHODS

Thirty-one
used. They were

adult the level

white of the

rabbits,
with

each
open

weighing
ether. The

between
skin on

two
the

and
back

three
of each

kilograms,

were

anaesthetised

shaved

from

knee

to the

calcaneus.

The

tendo

calcaneus

hind limb was was made taut by

TABLE
INTERVALS BETWEEN INJECTION

I
AND EXAMINATION

Time

after

injection

of

Number rabbits

of

hydrocortisone

45 minutes 24 hours
48 hours

3 3
3

72 hours
Iweek

3 3
4 4 4 4

2 weeks 4weeks 6weeks 8weeks

dorsiflexing suspension the right

the were side, one

foot. injected

Five milligrams percutaneously above

of hydrocortisone with a 25-gauge its insertion. into and 02

acetate in O2 millilitre of needle into the tendo calcaneus millilitre of O#{149}9 per cent sterile

the on

centimetre

saline rabbits at the

solution was injected with a separate needle were fed with laboratory purina rabbit chow
site
VOL.

an identical site on the left side. The observed daily for evidence of infection
calcaneal tendon.

of injection
54 B,
NO.

and

for

obvious
1972

rupture

of the

4,

NOVEMBER

729

730

P. BALASUBRAMANIAM

AND

K. PRATHAP

Fio.
Forty-five minutes after
with

1

injection
disorganised

of hydrocortisone
collagen.

into
(Haematoxylin

tendon.
and

Normal
eosin,

collagen x 240.)

bundle

continuous

FIG.
Forty-eight hours after injection of hydrocortisone

2
into tendon. Necrosis of collagen

with

acute

inflammatory

response

in a section

close

to the

paratenon.

(Haematoxylin
THE

and
OF BONE

eosin,
AND

x 240.)
JOINT

JOURNAL

SURGERY

THE

EFFECT

OF INJECTION

OF HYDROCORTISONE

INTO

RABBIT

CALCANEAL

TENDONS

731 sodium

The

rabbits

were (Table and

killed I). In the entire

at

varying

intervals

with

intravenous

injections with its junction

of

phenobarbitone carefully dissected

each instance tendon from

the tendo calcaneus the musculo-tendinous

paratenon was to its insertion

at the calcaneus was excised and fixed in 10 per cent formol saline. The fixed tendon was bisected longitudinally and embedded in paraffin. Sections were cut at 5 microns and stained with haematoxylin and eosin, elastic van Gieson, Masson’s trichrome and Alcian blue. In selected cases, von Kossa’s stain was used as well.

RESULTS

Immediate
injected and were present

change
control in this

(forty-five
tendons space.

minutes
showed Adjoining

after
separation blood

injection)-Sections
of collagen vessels were

from bundles. engorged

both hydrocortisoneA few red blood cells with blood and a few injection, a definite parallel arrangement of pale staining collagen collagen bundles (Fig. 1).

polymorphs had emigrated change in the appearance of the collagen fibres was

into the tissue. At the site of hydrocortisone of the collagen bundles was seen. The normal lost and was replaced by a disorganised area

in which nuclei of fibrocytes showed fragmentation which had undergone this change showed a woolly,

and dissolution. The eosinophilic appearance

Acute
change increase

inflammatory
in the in appearance the

phase
number of areas

(twenty-four
of the collagen polymorphs of necrosis

to seventy-two
bundles at the areas site with

hours)-Control
of injection. consisted

tendons
Tendons of loose, In material.

showed
There injected structureless longitudinal was

or damage These

to the fibroblasts.

no no with

hydrocortisone eosinophilic

showed material

of collagen.

interspersed

in some

basophilic

sections the necrotic collagen was continuous fibroblasts were not identified in the necrotic areas. closer to the paratenon showed vasodilation and (Fig. 2). Lesions centrally placed in the tendon

with normal collagen fibres. Nuclei of The cellular response was varied. Lesions an acute polymorphonuclear cell response very little or no cellular response (Fig. 3).

showed

F--.w-v;..

.

T

-

:
.

-

S

#{149}

-

-

c

-‘-

..

-

.

..,.,

-.-,.

..

..

‘L.-

‘‘i:

#{149}4

-..-

..
‘1

$---‘ * . .:U,_.

--.

-

.

-

-

-

:#{231}
‘ .

-s,---

:---------

--------

----.-

-

,___._J_ _*-__ -tt._#{149}_’

-

..

----

S

4.. 1#{149}.

-

-

.

‘

-.,,.--

-

-

S_S#{149}S.#{149}__i,%

FIG.

3 injection. Necrosis of collagen without

Centrally
VOL. 54 B,

placed 4,

lesion

forty-eight

hours

after

hydrocortisone

significant
NO. NOVEMBER

inflammatory 1972

reaction.

(Haematoxylin

and

eosin,

x 240).

732 Stage
showed

P.

BALASUBRAMANIAM

AND

K.

PRATHAP

of demolition
an increase

(seventy-two
in basophilic

hours

to one week)-Necrotic

areas

in the experimental

tendons

staining. The majority of the polymorphonuclear cells in the exudate were necrotic and the cellular infiltrate was predominantly mononuclear in type (Fig. 4). Many foamy macrophages were present by seventy-two hours. In sections from two tendons there were microscopic foci of recent collagenous necrosis continuous with older basophilic
necrotic areas. Nuclei of fibrocytes at the junction between necrotic

and

normal

collagen

showed

karyorrhexis
Sections from

and
control

pyknosis.
tendons

did

not

show

any

abnormality.

-..

-

,

.,‘

I

S_.-#{149}..S,e U

FIG.

4

One-week-old

lesion,

showing necrotic (Haematoxylin

collagen infiltrated and eosin, x 500.)

by mononuclear

cells.

Stage
some

of repair-By
lesions in

the

four weeks, fibroblastic hydrocortisone-injected

proliferation tendons.

was prominent Control tendons

at the periphery did not show

of any

abnormality. Repair of the necrotic lesion was more evident by six to eight weeks. The spindleshaped outline of the lesion could be made out, although it had contracted in size. Proliferation of fibroblasts was usually present at the periphery of the lesion and this gradually extended for a variable distance towards its centre (Fig. 5). There were some lesions which did not show any recognisable attempt at repair, the spindle-shaped areas of necrosis being filled by an acellular, amorphous eosinophilic material. Calcification of necrotic areas of collagen, confirmed with the von Kossa’s stain, was seen at the end ofeight weeks in certain experimental tendons (Fig. 6).

DISCUSSION

The been tears

mechanism

of tendon

rupture defect where

after

local

infiltration

of steroid

is not

clear.

It has

ascribed to an inherent in degenerating tendons

in the tendon (Cowan normal healing was

and Alexander 1961) or to minute inhibited by steroid therapy (Smaill

1961). Bedi and Ellis (1970) suggested that because of the avascular nature of the tendon, the steroid probably remained in it for a long time. This resulted not only in delayed maturation of fibrous tissue but also probably reduced the tensile strength of the tendon causing it to rupture with minimal effort. Whereas some is no objective evidence to support them. of these explanations have theoretical merit, there

THE

JOURNAL

OF

BONE

AND

JOINT

SURGERY

THE

EFFECT

OF INJECTION

OF HYDROCORTISONE

INTO

RABBIT

CALCANEAL

TENDONS

733

FIG.

5

Six-week-old

lesion,

showing
towards

proliferation
the centre.

of fibroblasts
(Haematoxylin

at the periphery.
and eosin, x 240.)

Necrosed

collagen

is seen

i;W -V.-

.
-lL

-

-5--

-

.‘

-

-__#{149}1___S
-t__.
-

---- z__
S

T-

FIG.

6
the tendon. (Von Kossa’s stain, x 240.)

Calcification
VOL.

in an

eight-week-old

lesion

in

54 B,

NO.

4,

NOVEMBER

1972

734 The present tendons causes seen showed as early study necrosis as forty-five

p.

BALASUBRAMANIAM

AND

K.

PRATHAP

demonstrates of collagen minutes

that infiltration of hydrocortisone into at the site of infiltration. An effect on after the injection of hydrocortisone,

rabbit calcaneal the tendon was the collagen Changes and death fibres tendons at

when

were
of the

a woolly eosinophilic also seen in the fibroblasts cell. The necrosed collagen No of the lesion. saline solution.

appearance after losing its parallel arrangement. of the collagen which showed nuclear destruction was necrosis seen to be continuous was seen with normal of the collagen control of collagen in any

the periphery injected with

The mechanism enzyme-mediated releases a protease,

of the necrosis of collagen action by the hydrocortisone. active at pH 7. This enzyme

is not known. In the skin is believed

It may be due to a direct or an it has been found that cortisol to activate the skin collagenase

and trigger the process ofcollagen breakdown (Woessner may account for the breakdown of collagen in the present was seen as early as thirty to forty-five minutes after possible that the necrosis of collagen may be due

1968). Although a similar mechanism study, this is unlikely because the effect the injection of hydrocortisone. It is action by the hydrocortisone.

to a direct

The inflammatory response following the necrosis of collagen was varied. Lesions close to the paratenon showed an acute inflammatory response, whereas those centrally placed in the tendon showed little or no response. The process of repair also closely followed a similar pattern. Peripheral response paratenon. In centrally placed lesions there was lesions showed repair by proliferation and no repair of the lesion even offibroblasts. This difference after eight weeks. in inflammatory to the vascular calcification.

repair seems to be related to the proximity of the It is also of interest that repair was often associated

necrotic area with dystrophic

CONCLUSIONS

This

experiment

demonstrates

that

infiltration

of

hydrocortisone

into

rabbit

calcaneal

tendons
The
complicated spontaneous

has a direct effect on the tendon,
of the lesion so produced by dystrophic calcification. rupture of tendons in patients

repair

producing necrosis is incomplete even

of collagen at the site of injection. after eight weeks, and is often may account for

Similar morphological changes receiving steroid infiltration.
and the Department of Medical

We thank Professor J. Francis Silva of Medicine, University of Malaya,

for his encouragement, for the photographs.

Illustration,

Faculty

REFERENCES BEDI, COWAN, ISMAIL, A. S. S., and
ELLIS,

W.

(1970): Annals

Spontaneous of Rheumatic S. (1961): Journal, and

Rupture Diseases, Simultaneous i, 1658. M. K.

of

Calcaneal 29, 494. Bilateral (1969):

Tendon Rupture Rupture

in Rheumatoid of Achilles

Arthritis Tendons after Due

after to

Local

Steroid
M. M., A.,

Injection.
and British

ALEXANDER,

Triamcinolone.

Medical R.,

BALAKRISHNAN,

RAJAKUMAR,

of Patellar

Ligament

Steroid
British

Infiltration. Journal ofBone and Joint LEE, H. B. (1957): Avulsion and Rupture
Medical LEE, M. MELMED, Journal SMAILL,
SWEETNAM,

51-B, 503. of the Tendo Calcaneus
Surgery, Tendon. Rupture 104. Tendon. and Tendon British of British the

after

Injection

of Hydrocortisone. i, 1829.
during Steroid

Journal, (1961): P. ofBone B. (1961): R. 397. (1969) (1965): E.

ii, 395. Bilateral and Joint Rupture Surgery, Rupture ofAchilles Bilateral 47-B, of Achilles Arthropathy MedicalJournal, Tendon Spontaneous Bilateral Calcaneal Therapy.

L. H.

G.

MedicalJournal, Journal

i, 1657.
of Bone and Joint Surgery,

: Corticosteroid

Rupture.

51-B, WOESSNER, Biology

J. F., Jun.
of Collagen,

(1968):
Part

Biological
B, p. 301.

Mechanisms
Edited

ofCollagen
by B. S. Gould.

Resorption.
London

In Treatise
and New York

on Collagen, : Academic

Volume
Press.

2,

THE

JOURNAL

OF BONE

AND

JOINT

SURGERY


				
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