New Frontiers in Pharmacology

No abstract available.

Effect of Thyroxine on the Cardiac Uptake of Catecholamines

The influence of thyroxine upon n the cardiac uptake of catecholamines was investigated in rabbits. A single injection of thyroxine(1.0m/kg) into rabbits did not affect the concentration of myocardial catecholamines. However, this dose of thyroxine greatly increased the cardiac uptake of catecholamine following injection of 2.0mg of norepinephrine as compared to that of untreated normal animals and it remained elevated for several hours. Similarly thyroxine also enhanced the accumulation of myocardial catecholamines following administration of dopa(60-80mg/kg) and epinephrine(1.0-1.5mg/kg).

Cardiac Catecholamines in Rabbits: Seasonal Changes and Norepinephrine Effect

In an attempt to determine whether myocardial catecholamines vary from season to season, their concentration in rabbits was measured throughout the whole year by the spectrophotofluorometric method. The highest concentration of cardiac catecholamine was observed in summer. Measurement of the atrial response to norepinephrine revealed no significant alteration during the entire period of the experiment.

The Effect of Beta-Adrenergic Receptor Blockade on the Atrial Refractory Period of Hyperthyroid Rabbits

Treatment of rabbits with thyroxine 1 mg/kg daily for three to six days produced a hyperthyroid state as evidenced by increase in the heart rate and PBI. The hyperthyroid animals exhibited a significant shortening of the atrial refractory period. Beta adrenergic receptor blocking agents, propranolol (l0(-6)M pronethalol (5 X 10(-5)M) or MJ-1999 (5 X 10(-4)M), completely blocked the shortening of the atrial refractory period produced by the treatment with thyroxin, and with norepinephrine. Consequently, the shortening of the atrial refractory period of rabbits treated with thyroxin appears to bs mediated through stimulation of the beta adrenergic receptor in the heart. From these results, it may be concluded that the stimulation of the beta adrenergic receptor plays an important role in the alteration of cardiac function found in hyperthyroidism, and that the beta adrenergic blocking agents may be useful in treatment of the cardiac complications of hyperthyroidism.

Medical Education and Medical Practice in Korea

No abstract available.

Tissue Catecholamines in Hypercholesteremic Rabbits

Hypercholesteremia was induced by cholesterol feeding of rabbits for 10 weeks. Gross examination of aorta of these animals showed an evidence of atheromatous lesions. The endogenous catecholamines in heart, adrenal gland, spleen, brain, liver and kidney of these hypercholesteremic rabbits were markedly reduced as compared to those of normal animals, respectively. There may exist some correleration between the serum cholesterol and tissue catecholamines.

Studies on the Survival of Skin Homografts in Rabbits Treated with Alloxan

In order to evaluate relationships between survival time of skin homografts and blood glucose levels a total of 187 viable homografts performed on 41 rabbits was observed Five group experiments were undertaken, namely normal, alloxan diabetic, insulin hypoglycemic, treated diabetic, and sugar-fed groups. In the diabetic group alloxan was given intravenously (40 mg/kg, 80 mg/kg and 129 mg/kg to 3 sub-groups respectively) and varied degrees of permanent diabetic states were confirmed. The survival of skin homografts in diabetic animals is strikingly prolonged (mean survivals of 11, 13, and 18 days respectively in groups receiving 40, 80, and 120mg/kg alloxan) compared with 7days for the control grafts. The degree of hyperglycemia was proportional to the amount of alloxan given and, likewise, the survival time of skin homografts was in general proportional to the blood glucose level.

The Influence of Rotatory Movement on the Tissue Catecholamines in Rats

The present study was designed to examine the possible relationship between the function of the labyrinth and the role of the sympathetic nervous system In experimental motion sickness produced by rotatory movement(8O r.p.m.). The catecholamines in the brain, the heart and the adrenal gland of rats were rapidly reduced to one half of normal values following exposure to rotatory movement. The pretreatment with streptomycin and dramamine completely prevented the depletion by the rotatory movement of the catecholamines in the brain, the heart and the adrenal gland, but scopolamine did not prevent the decrease. Bretylium or chlorpromazine signifcantly inhibited reduction of the catechol-amines in both of the brain and the heart. However they did not influence the decrease in the adrenal gland. The reduction of the tissue catecholamines in rotatory movement is presumed to be caused largely by activation of the sympathetic nervous system mediated through labyrinthine stimulation.

Effects of Inhalation Anesthetics on the Myocardial Catecholamines and its Response to Norepinephrine

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 other. The pulse rate and blood pressure were decreased marked1y in ether and the halothane anesthesia. the rate of beat of the isolated atria was not greately altered after anesthesia with ether or trichlore-thylene, while it was reduced after chloroform or halothane inhalation. The response of isolated atria to exogeneous norepinephrine was most prominent in the atria isolated from halothane anesthetized rabbits. Myocardial catecholamine contents were reduced uniformly after anesthesia with each anesthetics 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.

The Efficacy of Norepinephrine on Hemorrhagic Shock in Relation to Myocardial Catecholamines

The catecholamine content was examined in the myocardium of dogs subjected to hemorrhagic hypotension of 40mmHg for a duration of one to hive hours respectively. No marked changes were noticed within two hours after production of homorrhagic hypotension but a significant reduction was found at the end of three hours of hypotension. The reduction of myocardial catecholamines was progressively pronounced with the prolonging the hypotensive period over three hours. Dogs were bled rapidly to an arterial blood pressure of 40mmHg and maintained at this hypotensive level for four hours, followed by reinfusion of the withdrawn blood. Eight out of 11 dogs succumbed within l2 hours, showing a 73 per cent mortality. The myocardial catecholamines in the surviving dogs returned almost to the normal level within 12-15 hours after the blood reinfusion, while those in the dogs which succumbed showed the same low level which was produced during hemorrhagic hypotension. It was also shown that the reduced myocardial catecholamines resulting from the hypotension will not be restored immediately after the reinfusion of the withdrawn blood. When norepinephrine was infused at a rate of five to seven microgram/kg/min for an hour before the reinfusion of the withdrawn blood, five out of six dogs died within 12 hours, showing a 82 per cent mortality. This result appears to indicate that norepinephrine infusion during oligemic hypotension may hasten death or not decrease the mortality of the animals. On the other hand, when norepinephrine was infused at a rate of three microgramkg/min for an hour following reinfusion of the withdrawn blood five out of 15 dogs died, indicating a significant increase of survival rate from hemorrhagic shock. The myocardial catecholamines of surviving dogs and dogs which succumbed following the administration of norepinephrine after blood reinfusion were similar respectively to those of dogs which survived and of dogs which died after blood reinfusion without norepinephrine. When norepinephrine (3 microgramkg/min) was infused for hour following blood reinfusion in the dogs pretreated with either dibenzyline (3mg/kg) or dichloroisoproterenol (1mg/kg), the beneficial effect of norepinephrine on the survival rate from hemorrhagic shock appeared to be absent. The efficacy of norepinephrine on the survival from hemorrhagic shock was discussed on the basis of myocardial catecholamine depletion.

Effect of Serotonin on Gastric Secretion in the Dog

Heidenhain pouch secretion in response to small dose of serotonin was studied in conscious dogs. A single subcutaneous injection of 0.5 to 2.0 mg of serotonin produced no changes in spontaneous fasting secretion; however, the milk-induced secretion was greatly inhibited by the same dose. This inhibition was abolished by treatment of dibenzyline or LSD(d-lysergic acid die- thylamide). LSD alone enhanced the response of gastric secretion to milk. Constant intravenous infusion of serotonin, at levels of 3 to 10 microgram/kg/min was associated with a significant increase in the volume of gastric juice aspirated from three anesthetized dogs, but the acidity of juice varied very slightly. However, when histamine is given as much as 0.8 to 3 microgram/kg/min, a marked increase in both the volume and acidity was observed. A significant elevation of mucin content in the juice obtained from the Heidenhain pouch was seen in dogs receiving a single subcutaneous injection of 1.0 mg of serotonin. In case of histamine, the mucin content of pouch juice was not relatively increased and merely an increase in the total amount of mucin secondary to the volume increase was seen. The observed increase in mucin by serotonin was inhibited by LSD, BOL (2-bromo-d-lysergic acid diethylamide) or dibenzyline, and mildly by morphine. Atropine or hexamethonium did not block the response of mucin production to serotonin. The gastrointestinal motility elicited by serotonin was not affected by these agents. It is felt that the receptor(s) responsible for the mucin production in the dog belongs to the D-receptor types postulated by Gaddum and Picarelli.

Mechanism of the Positive Inotropic Actions of Quaternary Ammonium Compounds

The mechanism of the positive inotropic responses to quaternary ammonium compounds (tetraethylam-monium, tetra-n-propylammouium, trimethylethylamm-onium trimethyl-n-butylammonium, trimethyl-n-penty-lammonium, trimethyl-n-hexylammonium, trimethyI-phenylammonium, trimethylbenzylammonium, triethyl-phenylammonium and m-hydroxyphenyltrimethylam-monium) was examined on the atropinized papillarymuscle of cats. After pretreatment with dichloro-isoproterenol, all the quaternary ammonium compounds failed to produce their usual positive inotropic activities. Bretylium or TM-10, which specifically interferes with the release and/or synthesis of adrenergic mediators, rendered papillary muscle unresponsive to quaternary ammonium compounds but responsive to norepinephrine. Quaternary ammonium compounds also failed to produce their positive inotropic activity on papillary muscle whose catecholamines were a1most completely dep1eted by treatment with reserpine. Surgical removal of the sympathetic innervation to the heart resulted in a marked reduction of myocardial catecholamines. The positive inotropic responses to quaternary ammonium compounds were markedly suppressed in papillary muscle obtained from bilaterally-sympathectomized cats with degenerated postganglionic sympathetic nerve fibers to the heart. From the above results, it appears that quaternary ammonium compounds act at a common site to effect positive inotropic activities which are mediated via a catecholamine-release mechanism.

Urinary Excretion of 5-Hydroxyindoleacetic Acid in Normal Korean Adults and in Patients with Peptic Ulcer

Urinary excretion of 5-hydroxyindoleacetic acid was determined in 114 normal Korean adults and in 110 patients suffering from peptic ulcer. The amount of urinary 5-HIAA excreted during a period of 24 hours is fairly constant in each individual but varies widely between individuals. The mean daily output of urinary 5-HIAA in normal Korean adults is 1.93 +/-0.86 (S.D.) mg, which is similar to that found in normal Chinese adults. There is no significant difference between the urinary excretion of 5-HIAA in normal subjects and in patients with peptic ulcer. Furthermore, the amount of urinary 5-HIAA seems to be influenced by neither the sex of the subject nor by the degree of gastric acidity.

Kinetic Studies on the Competition Between Para-aminohippuric Acid(PAH) and Diodrast for Renal Trnsport in the Dog

No abstract available.