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
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
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.