Norepinephrine에 대한 심절(心節)의 감수성(憾受性)과 심절내(心節內) catecholamine량에 미치는 이, 삼전신마취제(二, 三全身麻醉劑)의 영향

Abstract

[한글]

[영문]

The growing frequency of cardiac arrest during anesthesia and surgery has been

the subject of considerable discussion in recent years. In 1954, the study of

Beecher and Todd was very illustrative. In their analysis of 599,548 Anesthetics,

they calculated that one death in 420 operations resulted from surgical errors,

whereas death due primarily to the anesthesia was estimated at one per 2,680

anesthetics, and the anesthetic technique was an important contributory causes of

death in one per 1,560 cases.

It has been well known that the poor risk patients including the geriatric,

pediatric and congenital or acquired heart anomality groups contributed greatly to

the surgical fatalities. Because of the pharmacological toxicity of the general

inhalation anesthetics, chloroform with its strong cardiotoxicity was limited to

use in local clinics, and trichlorethylene with the action of partial metabolism

and accumulation in the body was limited to less than 2 hours of use. Halothane

also with possible hepatotoxicity was considered contraindicated for use clinically

on jaundice patients.

Although ether has various side actions, it became popularized in many clinics

because of the large safety margin.

Sadove and Natof (1958), and Engel and Secher (1959) pointed out several

precipitating factors in cardiac arrest from anesthetic techniques: hypoxia,

hypercarbia, overdose of anesthetic agents, hemorrhage, hypotension, reflex

activity and hypothermia. Many causative factors have been reported by the

experimental or clinical study of cardiac arrest. If such a dangerous complication

occured, it was very difficult to treat. Recently various special operating room

monitorings were developed and it should reduce the mortality, if the resuscitation

has not been delayed. However, it is still uncerntain how to treat it most

effectively or what is the mechanism of the cardiac arrest.

During recent years, important factors of cardiac arrhythmias and arrest under

general inhalation anesthetics have been demonstrated to be related to increasing

sensitivity of the sympathetic nervous system, by the studies of Price et al.

(1959), Hamelberg et al. (1960), and Li and Etsten (1960). On the other hand,

cardiac arrhythmias and arrest during anesthesia were much improved with

beta-adrenergic receptor blockade, and this has been correlated with the effect of

the myocardial catecholamines by the study of Payne (1963), and Johnstone (1964a).

Furthermore, the relationship between the ventricular fibrillation under

hypothermia and the myocardial catecholamines was demonstrated by the study of Lee

(1963), in our department.

The sympathetic nervous system has long been known to be a factor in the

production of cardiac arrest, especially, when cardiac muscle has been previously

sensitized by the general inhalation anesthetics. The present study was undertaken

to investigate the relationship between cardiac sensitivity to norepinephrine and

the myocardial catecholamine content, during general inhalation anesthesia.

Methods

Rabbits weighing 2.0kg were fixed on the table in supine position. Endotracheal

tubes were inserted following tracheostomy. Inhalation anesthetic agents with

oxygen were administered by a nonrebreating system, with Wright-Belton or

Stephen-Slater valves connected with a Heidbrink anesthesia machine. Deep

anesthesia (stage Ⅲ, plane 2 or 3) was maintained for two hours. After two hours

of anesthesia, the chest was opened and the heart was imediately removed. The atria

isolated from the ventricles, were suspended in the muscle chamber containing 100

ml. of Tyrode's solution maintained at constant temperature of 38℃, with full

oxygenation.

Norepinephrine was added to the chamber and the changes of atrial beat and

contractile ampulitute were expressed as per cent. The catecholamine contents of

the cardiac muscle were determined by the Amico-Bowman Spectrophotofluorometric

procedure described by Shore and Olin (1958).

Results and Conclusions

1. The respiration, pulse and blood pressure changes were observed during tow

hours of anesthesia with ether, trichlorethylene, chloroform and halothane in the

rabbit, and the cardiac sensitivities to norepinephrine and myocardial

catecholamine contents were determined.

2. With ether inhalation (10%), it took thirty minutes to reach deep anesthesia.

During the initial thirty minutes, the respiratory rate was rapid and irregular,

but under deep anestesia, respiration became stabilized although the rate remained

rapid throughout. the pulse rate was rapid and the blood pressure was continuously

decreased by about 60% compared with normal controls at the end of anesthesia. The

rate in response to norepinephrine in the isolated atria after two hours of

anesthesia with ether was not notably altered in comparison with those of normal

controls, whereas contractile ampulitude was increased slightly. On the other hand,

the myocardial catecholamine contents were decreased moderately from the normal

controls.

3. Inhalation of trichlorethylene (0.5-1.0%) promptly induced deep and calm

anesthesia without association of irregularity or increased rate of respiration.

The pulse rate and blood pressure were gradually decreased. Especially blood

pressure was decreased by about 40% below normal controls. The isolated atrial rate

was moderately decreased but the atrial response to norepinephrine was moderately

increased, i.e. slightly increased in atrial rate and ampulitude. Nevertheless, the

myocardial catecholamine contents were decreased slightly below normal controls.

4. Inhalation of chloroform (0.5-1.0%) took forty minutes to produce deep

anesthesia. Until then, respiration was rapid and irregular, but when deep

anesthesia had been established, the respiration became calm and regular. The pulse

rate was rapid and the blood pressure was slightly decreased by about 20% of the

normal controls. The rate of the isolated atria after chloroform anesthesia was

reduced moderately. However the rate response to norepinephrine was slightly

increase, while ampulitude response increased more than five times in low

concentration over that of normal. the myocardial catecholamine contents were

decreased by one and a half of the normal controls.

5. Inhalation of halothane (1.0-2.0%) gave a similar induction course to

chloroform except a somewhat shorter time was required to reach deep anesthesia,

and the respiratory rate was slightly depressed until the end of anesthesia. the

pulse rate was slow with depression, and the blood pressure moderately decreased by

about 30% of the normal controls. The isolated atrial beat was significantly

decreased compared to other inhalation anesthetics, but the rate with

norepinephrine was increased one and a half times, and furthermore ampulitude

response increased significantly. The myocardial catecholamine contents were

decreased by one and a half of the normal controls.

In summary, the data obtained from present experiments demonstrated that among

several inhalation anesthetics, ether was the most irritable, resulting in marked

irregularity of respiratory movement, and halothane depressed respiratory rate more

than the others. The pulse rate and blood pressure were decreased markedly in ether

and the halothane anesthesia. The rate of isolated atria was not greatly altered

after anesthesia with ether or trichlorethylene, while it was reduced in the

isolated atria after chloroform or halothane inhalation. the response of isolated

atria to exogenous norepinephrine was most prominent in the atria of halothane

anesthetized rabbits. Myocardial catecholamine contents were reduced uniformly

after anesthesia with each anesthetic and most significantly with the halothane

inhalation.

From the above results, it may be concluded that the increasing cardiac activity

with general inhalation anesthetics is closely related to the quantitative changes

of the endogenous myocardial catecholamine contents.