국소 마취제가 흰쥐 골격근에 미치는 영향에 관한 형태학적 연구

Abstract

[영문]

[한글]

영구적으로 motor신경의 공급을 끊으면 골격근육에 위축이 초래되는 것은 일찍이 Ricke

r와 Ellenbeck(1869) 및 de Buck와 de Moor(1903)에 의해서 알려진 바 있었고, 그후 수종

의 국소 마취제가 국소 주사 후 골격근에 손상을 일으키는 것을 Tait등(1958), Brun(1959

), Pizzolato와 Mannheimer(1961)가 발표하였다. 이러한 위축 증세는 일개월간이나 계속

되며 두달째에는 다리의 큰 근육에서 대부분의 근섬유외 직경이 1/2내지 1/3로 작아지는

것을 Adams등(1962)이 발표하였다.

장시간 효력이 있는 국소마취제 bupivacaine(Marcaine)사용시 수일내로 골격근에 심한

위축이 일어 나는 것을 Sokoll등(1968)을 위시해서 Libelius등(1970), Benoit(1971), Ben

oit와 Belt(1970), Hall-Craggs차 Singh-Seyen(1975)이 보고한 바 있다. Stygall등(1979)

은 mepivacaine(Carbocaine)이 in vitro 실험에서 myoblast fusion의 저해와 myotute구조

의 파괴를 일으키는 것을 보고하였고 Basson과 Carlson(1980), Foster와 Carlson(1980)은

mepivacaine이 흰쥐에서 근독성을 일으키는 것을 보고하였다.

골격근의 미세구조에 대해서 Allbrock(1962)가 발표한 후 methyl bupivacaine의 세포독

성에 관한 미세구조의 변화를 Jirmanova와 Thesleff(1972)가 발표하였고 lidocaine이 백

서교근(masseter muscle)에 미치는 전자현미경적 영항에 대하여 Seibel등(1978)이 발표하

였으나 골격근에서 주사장소에 일어나는 변화에 관하여는 아직 보고가 없다.

Bupivacaine을 제외하고는 여러 국소마취제에 대해서 주사후 골격근에 미치는 영향에

대한 구체적인 연구가 없음으로 본 연구에서는 특히 많이 사용되고 있는 국소마취제로 am

ide제 lidocaine(Xylocaine)과 ester제 tetracaine(Pontocaine)을 근육주사후 백서골격근

gracilis posticus에서 일어나는 형태학적 및 조직 화학적 변화를 관찰하여 다음과 같은

결과를 얻었다.

1. Lidocaine과 tetracaine 주사후 근육의 무게가 1일에서 3일까지 대조군에 비해서 감

소되었으나, 그후 점차 증가하여 15일 내지 20일 사이에는 대조군과 같아졌다.

2. 주사 1일부터 3일까지 괴사, 위축현상 macrophage발생, plasma막불규칙 상태등의 섬

유파괴가 심하였으나, 15일 후부터는 재생이 나타났고 20내지 30일 후에는 완전히 정상으

로 회복되었다.

3. 근섬유의 직경이 대조군에 비해서 1내지 3일까지 감소되었으나 그후 점차 증가하여

15내지 25일 사이에는 대조군과 같아졌다.

4. 실험군에서 type Ⅱ 섬유형이 type Ⅰ 섬유형보다 선택적으로 파괴가 심하였다.

5. Tetracaine 실험군이 lidocaine 실험군보다 강하게 영향을 받아서 근육손상이 심하

였고 재생도 약간 지연되었다.

이상의 결과를 종합하여 보면 lidocaine과 tetracaine은 백서 gracilis근섬유에 급속한

손상을 주나 재생도 속히 일어나며 근육형별 또는 마취제의 종류에 따라서 근섬유반응의

정도에 차이가 있는 것을 알 수 있었다.

Morphological Studies on the Effects of Local Anesthetic drugs on Skeletal muscle

Chung Hyun Cho

Department of Medical Science The Graduate School, Yonsei University

(Directed by Prof. Tai Sun Shin, M.D.)

It has long been known that skeletal muscle undergoes atrophy following permanent

interruption of the motor nerve supply(Ricker and Ellenbeck, 1899; de Buck and de

Moor, 1903). Also many local anesthetic agents are known to damage skeletal muscle

following local injection(Tait et al, 1958; Brun, 1959; Pizzolato find Mannheimer,

1961; Benoit and Belt, 1972; Seibel et al, 1978). Reviews of the literature reveal

that relatively few studies have reported on the histopathological effects of local

anesthetics on skeletal muscle(Benoit, 1971).

The agents used and examination of tissue varied widely, and before 1970,

majority of investigators have reported muscle degeneration or necrosis only.

First, it was shown that skeletal muscle underwent profound atrophy within a few

days after having been treated with the long-acting anesthetic

bupivacaine(Marcaine) (Sokoll et al,1968; Libelius et al, 1970). However it was

also shown that bupicaine did not cause muscle atrophy, but produces focal muscle

necrosis followed by rapid resolution of the damage and complete regeneration, and

red type muscle fibers being more susceptible to damage than white fibers were

seen(Benoit and Belt, 1970; Jirmanov' and Thesleff, 1972). They concluded that the

drug had a specific myotoxic action.

Stygall et al(1979) have recently reported the inhibition of myoblast fusion and

the disruption of myotube structure in vitro by mepivacaine(Carbocaine) and other

local anesthetics. Basson and Carlson(1980), Foster and Carlson(1980) studied the

myotoxicity of the mepivacaine in the rat tibilis anterior or extensor digitorum

longus muscle. The ultrastructural aspects of the cytotoxicity of injected methy

bupivacaine was reported by Jirmanova and Thesleff(1972) and the ultrastructure of

rat masseter muscle was examined after a single injection of lidocaine(Seibel et

al, 2978). However there was no reports on the ultrastructure of skeletal muscle

after lidocaine or tetracaine injection.

Except far bupivacaine, there has been relatively little systematic work

documenting the myotoxic effects of single dose of other local anesthetics. In this

study, the myotoxicity of the local anesthetics lidocaine(Xylocaine) and

tetracaine(Pontocaine) was evaluated in the rat gracilis muscle through examining

morphological and histopathological changes.

In this study, 48 rats weighing approximately 200 gram were given single

intramuscular injection of lidocaine(0.2 ml of (0.8%) and tetracaine(0.2 ml of

0.4%) into gracilis poaticus muscle. Controls were performed by injecting

contralateral limbs with similar amount of 0.9% NaCl solution. Animals were killed

with an over dose of ether, 1, 3, 8, 15, 20 and 25 days after injection and muscle

were weighed and then prepared for light and electron microacopy. For measuring the

fiber diameters, photographs were taken of cross sections, enlarged 400×, and on

these the largest diameter and the diameter perpendicular to that in each fiber

were measured. The mean value of these two measurements was used for the

calculatien of the muscle fiber diameter. For ATPase stain, one day after

injection, muscle specimens were mounted on a chuck and chilled in liquid nitrogen.

Section of 10 um were cut in a crystat and stained myofibrillar ATPase(Padykula &

Herman, 1955).

The results are summarized as follows :

1. After one to three days treatment a marked atrophy of the gracilis poaticus

muscle was observed. The wet weight of the muscle was reduced to about 60 to 70% of

the contralateral untreated muscle. After 15 to 20 days muscle were returned to

normal size.

2. One to 3 days after injection, marcrophage appeared in damaged myofibers and

plasma membrane was irregular, nuclei with densely clumped chromatin were observed

in the atrophied muscle fibers. After 15 to 25 days histological pictures were

almost normal.

3. Mean diameter of muscle fibers were reduced to about 45 to 64% of that of the

control fibers.

4. Type Ⅱ fibers appeared more susceptible to damage than type Ⅰ fibers to

these drugs.

5. Tetracaine was more potent than lidocaine that muscle damage were more severe

and regeneration was delayed.

In conclusion although there were small differences in degree of changes,

lidocaine and tetracaine appears to effect upon rat gracilis muscle and cause rapid

destruction of skeletal muscel fibers which was followed by regeneration of new

fibers in the affected area. Also Type Ⅱ fibers appears more susceptible to these

drugs.