Role of catecholamine in ventricular fibrillation under hypothermia
External cooling by means of ice or cold water in cardiac surgery was first suggested by Rigelow. since then, in spite of the vast amount of basic and clinical work already done. It is abundantly evident that many additional studies are needed.
One of the major problems encountered in the use of hypothermia of 20℃ to 25℃ is the occurrence of ventricular fibrillation at those temperature levels. since the occurrence of this most serious complication, namely, ventricular fibrillation and cardiac arrhythmia constitutes a real danger to the clinical application of hypothermia. It is important that efforts continue to determine all the factors involved in their cause and prevention.
Cardiac muscle normally contains a certain amount of noreinephrine and the dramatic effect of this catecholamine on the cardiac muscle is well documented. It is therefore, conceivable that cardiac catecholamine might exert an influence on the susceptibility of heart muscle to tachycardia, ventricular fibrillation and arrhythmia.
If the reaction of the heart associated with a variable amount of catecholamine in the cardiac muscle is permitted to occur in the induction of hypothermia, the action of this agent on the hear has not to be differentiated from the direct effects of cooling. Hypothermia itself is stress enough to increase tonus of
The normal heart is supplied by an autonomic innervation and is subjected to action of circulating catecholamine which may be dissociated from the heart.
The studies presented in this paper were designed to provide further information about the cardio-physiological effects of reduced body temperature, with particular reference to the role of catecholamine in ventricular fibrillation.
Methods and Materials
Healthy cats, averaging three kg in weight were anesthetized with nembutal(20 to 30mg/kg) intraperitoneally. Then the trachea was intubated and the endotracheal tube was connected to a C.F.Palmer type A.C respiratior. The cats were immersed into an ice water tub until the desired body temperature was achieved. Esophageal temperatures were taken with a telethermometer. The action petentials of the heart muscle were simultaneously recorded on the Sanborn model 52 standard lead Ⅱ.
In some of cases the pH of blood and serum sodium and potassium were estimated before and after experiment. After the experiment the animals were killed ant the hearts were excised. The catecholamine content of the cardiac muscle was measure by the method of Shor eand Lin.
While lowering the body temperature about 1℃ every five to eight minutes, the pulse rate and a pattern of ECG were taken every five to ten minutes for each individual animal, although there was little variability in the results obtained.
There was a slowing of heart rate as the temperature fell. The average pulse rate of eight animals read 94/min at 31℃, 70/min at 27℃ and 43/min at 23℃ of esophageal temperature with not one exception, ventricular fibrillation occurred at a mean temperature of 20.3℃(21°-19℃)
The electrocardiogram revealed the presence of the abnormal P waves in each progressive cooling of the heart however ultimately, there was a marked delay in the P-R interval, QRS complex and Q-T interval. Inversion of the T waves was characteristic of all animals.
The catecholamine content of the heart muscle excised immediately after the occurrence of ventricular fibrillation was about thirty percent lower than that of the pre-hypothermic heart. The actual value was 1.0ug/Gm. compared to the prehypothermic value of 1.41ug/Gm. The changes of blood pH, serum sodium and potassium concentration were not remarkable.
Catecholamine has been thought to be an agent which stimulates the adrenergic receptor to cause ventricular fibrillation. Our interest in DCI originally sprang from a concern with the mechanism of its blocking the adrenergic receptor.
DCI(2-3mg per kilogram) was given intramuscularly. Thirty minutes later a procedure essentially similar to that previously described was employed in the production of hypothermia.
The direction of the observed change in pulse rate of the five animals studied was the same in this group as in the control group. Ventricular fibrillation did not occur in one of five animals, although body temperature was reduced even to 16℃. It succumbed at that low temperature. A loss of myocardial catecholamine after hypothermia was observed both in the cats prepared with DCI and in the normal animals. According to the findings in ventricular fibrillation was usually prevented by the administration of DCI. However the actual effect of DCI is not predictable.
In an experiment cats were given reserpine as a protection against excessive action of catecholamine during hypothermia. It was found that 24 hrs after reserpine(1mg/kg) was injected intramuscularly the concentration of catecholamine in cardiac muscle was reduced remarkably. this experiment disclosed a reduced incidence of venricular fibrillation. Six of the nine animals went into fibrillation at an average temperatiure of 19.6℃. After cooling of the whole body,
the catecholamine remmant dropped to 0.045ug/Gm.
In an attempt to elucidate further the role of myocardial catecholamine in the occurrance of ventricular fibrillation, the effect of brethylium which blocks the release of catecholamines was determined. Three to four hours after being given the intramuscular injection of 20 mg of bretyium the cats were placed in an ice-water bath. Ventricular fibrillation occured in four of the eight cats. The pulse rate was approximately the same as found previously in measuring rate of fall with cooling and in some cases was rather slower.
The occurrance of significant decrease in ventricular fibrillation in cats which were treated with bretylium under hypothermia, when the group was subjected to the administration of reserpine, was also established.
5. Norepinephrine or Dihydroxyphenylalanine(DOPA) and 2-Phenylcyclopropylamine HCI.(SKF-385)
The prevention of dissociation of catecholamine from heart muscle or a reduction in its content in heart muscle is not likely to produce ventricular Fibrillation. Therefore, this experiment was carried out on the cats whose myocardial catecholamine was elevated by the administration of norepinephrine or DOPA and SKF-385.
The cats were given norepinephrine 2 mg/Kg intramuscularly of DOPA 50 mg/Kg. and SKF-385 10 mg/Kg. Norepinephrine or DOPA and SKF-385 has been proved to cause significant increases in the catecholamine content of the heart muscle. Ventricular fibrillation occurred in all animals under hypothermia and the pulse rate increased remarkably compared with that of normal.
In this group comprising six animals which were treated with norepinephrine or DOPA and SKF-385, ventricular fibrillation occurred at average temprature of 21.6℃.
Catecholamine content of cardiac muscle markedly decreased after hypothermica but showed significantly high value compared to that observed in control.