Ouabain 中毒으로 因한 心不整搏動에 미치는 各種藥物의 影響

Abstract

[한글]

[영문]

Digitalis is known to be an unique cardiotonic in the treatment of congestive heart failure. The toxic manifestations of digitalis are extensions of its therapeutic effect largely due to its cumulative action. The toxic manifestations may be divided into extracardiac and cardiac. The cardiac effects can be lethal and because of their danger, they are the prime concern in digitalis poisoning. They may include the various stages of AV block, premature systoles and tachycardia, paroxysmal atrial tachycardia with AV block, and finally ventricular fibrillation.

The most important and serious symptom of digitalis intoxications is ventricular fibrillation, which progresses to death. Although there are many reports concerning the mechanism and treatment of digitalis poisoning the adequate answer is not yet found.

Mendez et al. (1961) reported that in sympathectomized dog with or without adrenalectomy, digitalis causes death by cardiac arrest without ventricular fibrillation, and the lethal dose of the digitalis is increased. Robert et at. (1963) showed a reduction in digitalis-induced arrhythmias in the isolated cat

papillary muscle treated with adrenergic blocking agents. These observation suggested that sympatho-adrenal system may participate in the genesis of ventricular fibrillation clue to digitalis poisoning. On the other hand, Morrow et at. (1963) found that equal doses of ouabain were required to produce cardiac arrhythmias in both normal and sympathectomized dogs. Consequently, they concluded that catecholamines do not play any important role in digitalis-induced arrhythmias.

In an attempt to explore the genesis of cardiac manifestations in digitalis poisoning, the present experiment was undertaken to investigate the role of catecholamines in the ventricular fibrillation induced by ouabain. The protective capacities of quinidine and procaine amide against ventricular fibrillation were also investigated.

The animals used were dogs weighing 7 to 13 kg. Under pentobarbital sodium anesthesia, the blood pressure was recorded from right femoral artery and ouabain (0.2 μg/kg/min) was continuously injected through right femoral vein. The electrocardiogram was recorded with a Sanborn model No. 52, electrocardiography. In order to determine the concentration of tissue catecholamines left ventricle was immediately reseated after experiment, which was analyzed according to the modified

method of Shore and Olin (1958) using Aminco-Bowman spectrophotofluorometer.

The Results are Summarized as Followings:

1. In normal dogs, the continuous infusion of ouabain produced ventricular fibrillation within an average of 48 min with lethal dole of 9.6 μg/kg. The myocardial catecholamine content was lower than that of the dogs in which ouabain was not given.

2. In dogs pretreated with MJ-1999, a beta-adrenergic blocking agent, the continuous infusion of ouabain produced ventricular fibrillation at an average of 54 min in only 3 cases among 5 dogs. The average lethal dose of ouabain in 5 dogs was 10.8 μg/kg. The cardiac catecholamine contents of theme animals were similar to those observed in control dogs.

3. Pretreatment with nethalide, another beta-adrenergic blocking agent, prevented the occurrence of ventricular fibrillation due to the infusion of ouabain in one out of two dogs. The average lethal dose of ouabain in these two dogs was 13.8 μg/kg.

4. In dogs which myocardial catecholamines were almost depleted by the administration of reserpine, ouabain caused cardiac arrest without ventricular fibrillation in 2 out of 5 dogs. The average lethal dose of ouabain in these 5 dogs was 18.2 μg/kg which is significantly larger than that in the control dogs.

5. In the dogs pretreated with quinidine, ventricular fibrillation appeared in an average of 65 min due to ouabain infusion with the lethal dose of 13.0 μg/kg. But the cardiac catecholamine content was similar with that of the control dogs.

6. In the dogs given procaine amide, ventricular fibrillation occurred by ouabain infusion within an average of 53 min with the lethal dose of 10.6 μg/kg, which was larger and prolonged more than that observed in control dogs.

7. After the pretreatment of promazine, ventricular fibrillation occurred by ouabain at an average of 53 with the lethal dose of 10.6 μg/kg. The catecholamine content of heart was decreased.

8. The blood pressure elevated slowly along with the infusion of ouabain in normal dogs. The elevation of blood pressure was more marked in dog? pretreated with MJ-1999 and nethalide, and was less marked in reserpinized animals.

From the above result, it may be concluded that catecholamines play a martial role in producing ventricular fibrillation induced by ouabain.