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
Effect of inhalation anesthetics on the myocardial catecholamines and its response to norepinephrine
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.
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
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
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
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.