Part 1: Extracorporeal Hypothermia in Normal and Reserpinized Dogs In 1950 Bigelow et al. suggested the physiological feasibilty of complete occlusion of the circulation to the heart to permit intracardiac operations. this was based upon experimental observations that an almost linear reduction of oxygen consumption occurs with decrease in body temperature. Since that time, hypothermia has been extensively employed not only for intracardiac surgery, but also for other surgical procedures.
The most serious complication assoicated with deep hypothermia is the occurrence of ventricular fibrillation. In man, by surface cooling, 28°∼30℃ was the lowest safe limit to which the body temperature could be reduced without danger of ventricular fibrillation, but in this temperature range the circulation to the heart could be interrupted for only ten minutes.
Considerable work has been done to determine the etiology of ventricular fibrillation but investigators failed to produce a solution. Swan et al. (1955) produced a respiratory alkalosis by pulmonary overventilation and reduced the incidence of ventricular fibrillation in hypothermic dogs; Osborn(1953) prevented ventricular fibrillation in dogs cooled below 19℃ by maintaining a high serum bicarbonate; Riberi et al. (1956) reduced the incidence of ventricular fibrillation by blocking the sino-atrial node with local anesthesia; Lee (1963) reported
catecholamines in the cardiac muscle play an important role in the production of ventricular fibrillation in hypothermic cats.
Perhaps the most promising approach to deep hypothermia is to be found in the combination of extracorporeal circulation with a pump oxygenator and hypothermia. The inclusion of a heat exchanger in the extracorporeal circuit will permit more precise control of cooling and reqarming, and the danger of ventricular
fibrillation could be reduced. Kenyon et al.(1959) reported survival of dogs cooled below 5℃ with periods of complete circulatory arrest of up to 45 minutes with this technique.
In the present study dogs were cooled to an esophageal temperature of 10℃ by means of extracorporeal circulation with a pump oxygenator and heat exchanger, and rewarmed after one hour's ?uration of complete circulatory arrest. The observations on the circulatory system and histological changes of brain tissue were compared with those of reserpinized dogs.
The results are summarized as follows:
1) Cooling time to the esophageal temperature of 10℃ averaged 73.4 minutes (range 30∼150 minutes). The rectal temperature averaged 14.4℃ (range 11°∼18℃) when the esophageal temperature reached 10℃. During periods of circulatory arrest
the esophageal temperature was raised by 1.2°∼4.7℃. Rewarming time to an esophageal temperature of 35°∼36℃ averaged 55.7 minutes.
2) Arterial pressure fell progressively as the body temperature decreased, and returned to almost precooling level on rewarming. Venous pressure level did not show a constant value.
3) Ventricular fibrillation occurred in one of 5 dogs at the esophageal temperature of 14℃. Cardiac arrest occurred at an average esophageal temperature of 14.7℃. On rewarming there were 3 cases of ventricular fibrillation at 23℃ and 25℃. Two of these returned to sinus rhythm after electric shock, and the other recovered spontaneously. The remaining 2 cases returned to sinus rhythm at 27℃ and 32℃ respectively.
4) During cooling, the heart rate slowed progressively as the body temperature fell until the point of cardiac arrest. The ECG showed a progressive decrease in cardiac conduction, manifested by a broadening of the P wave and QRS complex. The P·R and Q·T interval became progressively longer. Elevation of the ST segment and inversion of the T wave were noted, but they returned to normal range on rewarming. The heart contraction started at about 16℃.
5) The fully dilated pupils during circulatory arrest became miotic at 34°∼36℃, and eye-lash reflexes were present at 31°∼36℃. Spontaneous respiration resumed at about 34℃. In the majority of cases there was some response to painful stimuli, but all died within 6 hours after the experiment.
6) The important histological changes of the brain tissue were acute degeneration of neurons and interstitial edema. Severe edema in the white matter, especially near the ventricles, was noted. By region, the edema was more marked in the temporal lobes and less in the cerebellum and pons. The main changes in neurons
were swelling of the cytoplasm and vacuolization, and in severe cases there was loss of the cell membrane. However, there was no clear-cut change in nuclei and Nissl's bodies. Neither the degeneration of glial cells and the myeline sheath nor necrosis and inflammatory change could be found. The above findings are compatible with those changes seen in acute anoxia.
7) In the reserpinized dogs, cooling and rewarming times were somewhat shortened compared with the control group. During cooling there was no ventricular fibrillation in 5 dogs, but on rewarming 3 cases of ventricular fibrillation were seen. The ECG findings were not peculiar, except for bradycardia, compared with
control group. The histological changes of brain tissue were more marked in reserpinized dogs.
Part Ⅱ: The Effect of Reserpine, Qeinidine, and Procaine Amide on Ventricular Fibrillation under Hypothermia
Although ti has been known that ventricular filbrillation is the most important complication during hypothermia. much investigation has failed to show the exact nature of the etiology of ventricular fibrillation.
Recently there has been considerable research on the relationship between sympathetic activity and ventricular fibrillation under hypothermia, but there are many point on which the evidence is conflicting.
Montgomery et al. (1954) reported that ventrcular fibllation under hypothermia was caused by an increased sensitivity of the heart to sympathetic activity.
Furhman et al. (1944), and Garb and Penna (1956) reported that the sensitivity to exogenous epinephrine is increased under hypothermia. Browen ans Cotton (1956) showed an increased blood concentration of catecholamines during hypothermia.
Shumacker et al. (1956) reported a reduced incidence of ventricular fibrillation following sympathectomy. Mendez et al. (1961) pointed out that sympathectomy and adrenalectomy effectively prevented ventricular fibrillation. Lee (1963) reported that catecholamines in cardiac muscle play an important role in producing ventricular fibrillation under hypothermia.
Meanwhile. Reissmann and Kapoor (1956) observed the onset of ventricular fibrillation in the denervated heart, Covino et al. (1954) reported the occurrence of ventricular fibrillation under hypothermia following medication with adrenergic blocking agents.
The above mentioned facts indicate that the relationship between ventricular fibrillation and sympathetic activity demands more detailed study. This experiment was designed to investigate the possible role of catecholamines on ventricular fibrillation under surface hypothermia, and the results were compared with the data obtained from quinidine and procaine amide medication.
Healthy cats were anesthetized with pentobarbital sodium, 25-35 mg/kg, intraperitoneally and hyperventilated by a mechanical respirator. The cats were cooled by surface hypothermia as described by Lee (1963). The esophageal temperature was taken with a telethermometer and the ECG was recorded. The catecholamine content of the heart muscle, spleen, and adrenal gland was measured by the method of Shore and Olin (1958).
1) In normal cats, as the body temperature decreased, the heart rate showed progressively. The electrocardiographic changes were a marked prolongation of the P·R interval, QRS complex and Q·T interval, and inversion of the T wave. Ventricular fibrillation occurred in all cats at an average temperature of 20.7℃.
The catecholamine content of the heart muscle, spleen, and adrenal gland immediately after ventricular fibrillation was lower than that of the normothermic cats.
2) In the reserpinized cats, reserpine in a dosage of 2 mg. per kg. of body weight was given intraperitoneally 24 hours prior to the experiment. As the temperature fell, except for a slow pulse, the ECG revealed on great difference compared with a control group. Five of 7 cats went into ventricular fibrillation at an average body temperature of 18.4℃. The catecholamine content of the heart muscle, spleen, and adrenal gland was very small.
3) In the cats given quinidine in a dosage of 30 mg. per kg. of body weight intraperitoneally, the ECG findings, as the body temperature fell, were not different from those of the control group. No ventricular fibrillation occurred even at 15℃. The catecholamine content of the heart muscle, spleen, and adrenal
gland was almost similar with those of the control cats.
4) In this experiment cats were given procaine amide in a dosage of 0.3 mg. per kg. per minute as a continous intravenous infusion. The ECG findings during surface cooling revealed no difference from those of cats given quinidine. There was no
ventricular fibrillation at 15℃. The catecholamine content of the heart muscle, spleen, and adrenal gland was much lower than those of control cats. From the above experiment it is possible to conclude that catecholamines play a partial role in producing ventricular fibrillation under hypothermia. However, there is another important factor, as shown by the fact that, in this study, quinidine and procaine amide prevented ventricular fibrillation quite effectively.