출혈성 Shock에 관한 연구

Abstract

[한글]

[영문]

Part Ⅰ. Hemorrhagic Shock and Cardiac Catecholamines

It is generally known that vasoconstriction is a prominent feature of the early

stage of hemorrhagic shock in experimental animals, and that this is a protective

mechanism mediated through the sympathetic nervous system to maintain a blood

supply to vital organs. Freeman et al.(1938), however, pointed out that, although

animals with intact sympathetic nervous system were able to compensate more readily

to acute hemorrhage than completely sympathectomized animals, the mortality rate

was greater in intact than in sympathectemized animals if the hemorrhagic

hypotension was prolonged. This concept was supported by many other workers (Gope,

1911; Pillcher et al., 1914; Bayliss, 1923). Furthermore, it has also been shown

that the adrenergic blocking agent such as dibenamine can protect from the lethal

effects of hemorrhagic hypotension (Wiggers et al., 1950;Levy et al., 1954;

Lillehei et al., 1964). These observations lead to the proposal that decrease in

sympathetic nervous system response might be pertinent for a decrease in mortality

following hemorrhagic shock. In contrast to the above reports, Chien and Hitzig

(1960) determined the amount of blood withdrawal which produced death in 50% of

intact and sympathectomized dogs and concluded that the presence of the sympathetic

nervous system increased the tolerance to hemorrhage shock.

Although there is controversial reports concerning the effects of sympathetic

nervous system on hemorrhagic shock, it is obvious that the adrenergic

neurotransmitter, i.e. catecholamines play an important role in the lethal effects

of hemorrhage. In addition, Park(1961) demonstrated that myocardial catecholamines

were significantly reduced during hemorrhagic hypotension. Coleman and

Glaviano(1963) also showed that catecholamines in the heart, spleen, brain, and

liver were markedly decreased during relationship between the endogenous tissue

catecholamines and hemorrhagic shock.

The present experiment, therefore, was designed to explore the role of cardiac

catecholamines in the mortality of hemorrhagic shock.

Healthy albino male rabbits, weighing approximately 2.0kg, were anesthetized with

urethane (0.4g/kg) given intravenously. A carotid artery was exposed and was

directly connected to a mercury manometer for continuous recording of changes in

arterial blood pressure on smoked drum. The other carotid artery was also exposed

in order to withdraw blood. Endotracheal intubation was employed so that a free

air-way maintained at all times and heparin (3.0-5.0mg/kg) was injected

intravenously to prevent blood coagulation.

Initial 10.0ml of blood per kg of animal weight was rapidly withdrawn and

thereafter 2.0ml/kg of blood was withdrawn at an interval of 10 minutes until the

animal died.

1. Following the initial bleeding of 10.0ml/kg in normal rabbits, the mean

arterial pressure was rapidly dropped to 60mmHg from 110mmHg. Thereafter, the blood

pressure was gradually reduced until death. The average survival time and total

bleeding volume for these animals were 84 minutes and 28.0ml/kg, respectively.

Examination of the cardiac catecholamines soon after death revealed average

1.18μg/g, which is significantly smaller than that of normal(1.68μg/kg).

2. The injection of norepinephrine (2.0mg/kg) markedly elevated the concentration

of myocardial catecholamines in rabbits. At the end of one hour after injection of

norepinephrine, the animals were subjected to hemorrhagic shock by the procedure

described previously. The average survival time for these animals was 62minutes,

indicating that pretreatment of norepinephrine hasten the death due to hemorrhagic

shock. The average bleeding volume was 18.0ml/kg and the cardiac catecholamine

concentration was 1.21μg/g which is not significantly different from the control

animals.

3. The intraperitoneal injection of reserpine (3.0mg/kg) depletes almost

completely the cardiac catecholamines of rabbits within 24 hours. At the end of 24

hours after the injection of reserpine, the animals were subjected to hemorrhagic

shock. The total bleeding volume taken until death was 30.0ml/kg. The average

survival time for those rabbits was 101 minutes which is significantly longer than

that observed in control animals.