Experimental study on the changes of serum free fatty acid and blood sugar during hemorrhagic shock
[영문]It has been known that the pronounced hypotension resulting from hemorrhage gives rise to compensatory stimulation of the adrenosympathetic system, which leads to an increase of liberation of catecholamines from sympathetic nervous system and
adrenal medulla. It is obvious, therefore, that numerous physiological and biochemical changes during the hemorrhagic hypotention might be mediated through the increased liberation of catecholamines. Although an extensive studies have been reported on changes of protein and carbohydrate metabolism in hemorrhagic shock a few studies on the changes of lipid metabolism have been reported. Levenson(1961) observed a marked increase of serum lipid content during hemorrhagic shock and also noticed a marked elevation of serum free fatty acids. He suggested that these effects were due to mobilization and accelerated metabolic breakdown of lipids which might be resulted by sympathetic stimulation as a cause.
To elucidate the mechanism of this, author studied the changes of serum free fatty acids and blood sugar with relation to catecholamines during experimentally induced hemorrhagic shock in dog.
Healthy male mongrel dogs weighing approximately 15kg were used. Under the general anesthesia with pentobarbital, rapid hemorrhage was produced from the femoral artery maintaining blood pressure level of 40 mmHg measured by the manometer connected with the opposite femoral artery throughout the experiment.
Serum free fatty acids (FFA) and blood sugar were measured by the methods of dole (1956) and Folin-wu, (1920) respectively. tissue catecholamine was measured by Shore and Olin method (1958) using Aminco-Bowman spectrophotofluorometer.
1. Dogs were bled rapidly to an arterial blood pressure of 40 mmHg and maintained at this level for four hours. The serum FFA rapidly increased up to 66% above normal at two hours after the initiation of bleeding, and returned to normal level within for hours. Blood sugar increased to 35% above normal at 15min. and returned to normal in two hours. The tissue catecholamines in heart, spleen, liver and adrenals markedly diminished at four hours after the initiation of hemorrhage.
2. Reserpine is known to deplete catecholamines from their stores. Twenty-four hours after the intraperitoneal injection of reserpine 1mg/kg, dogs were bled to an arterial blood pressure of 40 mmHg and maintained at this level of hypotension. The serum FFA showed essentially no changes during the course of this experiment but the blood sugar gradually increased reaching up to the double of the normal level at 3 hours after the beginning of hemorrhage and thereafter gradually returned to the normal level.
3. Dogs were premedicated with bretylium tosylate which blocks the release of catecholamines from sympathetic nerve endings. At the end of 4 hours after the injection of bretylium 10 mg/kg, the animals were subjected to hemorrhagic hypotension of 40 mmHg. There was no significant changes in the serum FFA but the blood sugar rapidly increased up to 60% above normal level within one hour after the beginning of hemorrhage.
4. Dogs were injected with P-286 (2.5mg/kg), which was reported to block the release of catecholamines from adrenal medulla, and subjected to hemorrhagic hypotension by the procedure described above. The serum FFA was markedly increased, reaching the maximum at 2 hours.
On the other hand, the blood sugar showed no significant changes throughout the course of hypotension.
5. In an attempt to examine the effects of norepinephrine and epinephrine on the serum FFA as well as the blood sugar, these drugs were continuously injected intravenously at the rate of 1.0㎍/kg/min. into the normal dogs. The continuous injection of norepinephrine caused an increase of serum FFA approximately 85% above the normal level but produced no significant changes in the blood sugar. On the other hand, the continuous injection of epinephrine markedly increased the blood sugar with a slight elevation of serum FFA.
6. At the end of 2 weeks after the adrenalectomy was performed in the dogs, the animals were subjected to hemorrhagic hypotension of 40 mmHg. The serum FFa and blood sugar were simultaneously decreased almost to the half of the normal level at the beginning of hemorrhage and thereafter maintained at this level during the course of this experiment.
In summary, the elevation serum FFA during the acute hemorrhage is largely due to norepinephrine liberated from sympathetic nerve ending and the change of blood sugar largely epinephrine liberated from adrenal medulla.