Wilbur A. Thomas

Myocardial Infarction in Rats Fed Diets Containing High Fat, Cholesterol, Thiouracil, and Sodium Cholate

Investigators have produced arteriosclerosis in experimental animals by dietary means for almost half a century. In contrast to the situation in man, however, all previous reports indicate that complicating thrombosis and infarction have been extremely rare in experimental animals. The current report presents dietary regimens by means of which the authors have produced significant numbers of myocardial and renal infarcts in rats (6 of 10 in one group and 4 of 10 in each of 2 others). It is notable that thrombosis occurred before the appearance of severe structural changes in the arterial walls, although abundant fat could often be demonstrated histochemically.

An Electron Microscopic Study of Myocardial Ischemia in the Rat

Myocardial infarcts were produced in rats by ligating the anterior descending branch of the left coronary artery. After one hour, changes in the ultrastructure of myofibers in the infarcts were readily demonstrated by electron microscopy. These changes became progressively severe with time, and consisted primarily of swelling of mitochrondria and sarcoplasmic reticulum followed by increased lipid droplets and myolysis. Autolysis Atolysis of myocardium was also studied and the changes found to be similar to those of myocardial infarcts, but more uniform and slightly delayed in development. Perhaps the early ultrastructrural changes are related to hyperosmolarity of mitochondria and sarcoplasmic reticulum, especially after cell death. It is hoped that definition of ischemic ultrastructural change will be useful in defining electron microscopic lesions in other forms of myocardial damage.

Incidence of myocardial infarction correlated with venous and pulmonary thrombosis and embolism∗: A geographic study based on autopsies in Uganda, East Africa and St. Louis, U. S. A.

Abstract Recent autopsy records at Washington University in St. Louis and Makerere College in Uganda, East Africa were reviewed to determine the incidences of venous thrombi and pulmonary thromboembolic phenomena, as well as the incidences of myocardial infarcts, in three groups of patients: (1) St. Louis white patients, (2) St. Louis Negroes, and (3) Uganda Negroes. The incidence of myocardial infarcts was high in St. Louis white patients, intermediate in St. Louis Negroes and practically nil in Uganda Negroes; the only infarct found in Uganda among 1,427 patients over forty years of age was a small healed one. The incidence of venous thrombi and pulmonary thromboembolic phenomena closely paralleled the incidence of myocardial infarcts in the three groups. The studies reported herein suggest that differences in the general tendency of the blood to clot and/or lyse account, at least in part, for the differences in the incidences of coronary thrombosis and myocardial infarction that exist between autopsied Ugandans and St. Louisans. Further investigation must be carried out utilizing many technics before the suggestion can be established as fact. Other studies will then be necessary to determine the precise nature of the difference and the reason for it, i.e., dietary, emotional or genetic. Probable, but as yet unestablished, differences in the degree of atherosclerosis present in the three groups may also contribute to the differences in incidences of myocardial infarction, but since the local factor of atherosclerosis is not present in veins, it could not account for the observed differences in evidences of venous thrombosis.

Myocardial Infarction in Patients Treated with Sippy and Other High-Milk Diets An Autopsy Study of Fifteen Hospitals in the U.S.A. and Great Britain

A study has been made of the incidence of myocardial infarcts among 3 groups of autopsied patients who were matched for age, sex, race, and place and period of death: (1) patients with peptic ulcers who had been treated with a Sippy diet or milk products, (2) patients with peptic ulcers who were not known to have been so treated, (3) a group consisting of non-ulcer patients matched with the other 2 groups. In the U.S.A. the incidence of myocardial infarcts was more than twice as high in the ulcer patients treated with Sippy diet than it was in either of the other 2 groups. The differences in each case were statistically highly significant. There was no significant difference in the incidence of myocardial infarcts between the ulcer patients not treated with the Sippy diet and the non-ulcer controls. Differences and similarities of the same degree were noted among corresponding groups from Great Britain. It is tempting to think that the high incidence of myocardial infarcts among the Sippy-treated patients was a result of the butter-fat content of their diets. Mere association, however, does not constitute proof and further study is needed before definitive conclusions are drawn.

Chemico-anatomic studies in the geographic pathology of arteriosclerosis: Comparison of adipose tissue fatty acids and plasma lipids in diabetics from east africa and the united states with different frequencies of myocardial infarction

Abstract Three groups of patients with diabetes mellitus examined at autopsy, a North American white group, a North American Negro group and an East African group, were found to have a high, intermediate and low frequency (approximately 50, 25 and 0 per cent, respectively) of myocardial infarcts. It appears that while diabetes mellitus predisposed to the occurrence of myocardial infarction in the North American white diabetics, factors other than diabetes per se were contributory. Because of the suggested relationship of lipids to myocardial infarcts, the fatty acids of adipose tissue and plasma lipids were measured in age- and sex-matched groups of diabetic patients from the same hospitals from which the autopsy data were drawn. This was done to learn if lipid values were different in these three diabetic groups with a disparate occurrence of myocardial infarcts. Despite the wide difference in the frequency of myocardial infarcts in North American whites and Negroes, only small differences were found in the adipose tissue fatty acids of the two groups, and no significant difference was present in the plasma cholesterol levels. If plasma cholesterol serves as even a rough indication of the possible occurrence of myocardial infarction in a group, one would expect the frequency of myocardial infarcts confirmed at autopsy to increase in Negro diabetics in the years ahead. The East African diabetic group showed, in addition to minor adipose tissue fatty acid differences, a considerably lower adipose tissue oleic acid level than the North American white or Negro diabetic groups. A similar low adipose tissue oleic acid level has been noted in Guatemalan nondiabetics, who also have a low incidence of myocardial infarcts as compared to North American nondiabetics. Whether or not this finding of a low adipose tissue oleic acid level in groups with a low incidence of myocardial infarction is biologically significant must await further work. The plasma cholesterol of the East African group was significantly lower than that of either North American group, possibly because of their lower quantitative dietary fat intake. It is possible that the low adipose tissue oleic acid value of the East African group is the result of a different qualitative fatty acid intake, but dietary studies so far carried out in Uganda are not adequate enough to warrant this conclusion. This study shows that three groups of diabetics with differing frequencies of myocardial infarcts by autopsy evidence have, as well as differences in adipose tissue fatty acids and plasma lipids, many similarities, at least in the case of two groups, North American Negro and white diabetics. It will be of great interest in the case of East African diabetics, with their socioeconomic and dietary patterns possibly becoming more similar to the American groups, to see whether or not their lipid patterns and their occurrence rates of myocardial infarction will also change.

Dietary production of myocardial infarction in rats; anatomic features of the disease.

Abstract Arterial thromboses with myocardial and renal infarcts occur in a large percentage of rats fed a known atherogenic diet to which is added large amounts of saturated fats. Thromboses occur before the formation of significant local intimai lesions, indicating that some hematologie factor is involved. The mechanism of formation of the thrombi is unknown. The altered state produced in these animals is also characterized by marked accumulations of fat in the liver, spleen, lymph nodes and adrenal cortex as well as the presence of large fat globules lodged in the capillaries of the lungs and renal glomeruli.

The Role of Pulmonary Hypertension and Thromboembolism in the Production of Pulmonary Arteriosclerosis

Thromboembolism and pulmonary hypertension have been assessed as factors in the production of pulmonary arteriosclerosis. A study was made of autopsy records and tissue sections from 59 cases of congenital heart disease with anomalies permitting shunting of blood from the systemic to the pulmonary circulation and 31 cases of pulmonary stenosis with septal defect. Pulmonary arteriosclerosis was found to be common and of equal frequency in the two groups of cases, indicating that hypertension is not a necessary factor. There was a close correlation between the presence of pulmonary arterial thrombi and pulmonary arteriosclerosis.

Methods for comparing effects of various fats on fibrinolysis.

Summary In experiments reported herein. 2 new methods have been utilized to compare the biologic effect of 3 dietary fats. (1) In Exp. 1 a study has been made in rabbits of the effect of single meals of butter, corn oil, coconut oil and water on fibrinolytic activity of blood (drawn 3 hours after feeding and measured by a technic utilizing streptokinase to activate profibrinolysin) in vitro under controlled conditions. Lysis time so measured was significantly prolonged in rabbits fed butter as compared with those fed either corn oil, coconut oil or water. Meals of corn oil and coconut oil had no more effect on lysis time than did water. (2) In Exp. 2 the effect of butter, corn oil, coconut oil and saline added in vitro on fibrinolytic activity of clotted human plasma was measured by a technic utilizing streptokinase to activate profibrinolysin under controlled conditions. Under these conditions butter markedly and significantly (p = 0.01) prolonged lysis time of human plasma, whereas corn oil and coconut oil had a lesser effect. (3) Other substances and approaches must be studied before definitive conclusions can be drawn regarding relationships of various fats to arteriosclerosis and thrombosis in man. Our experiments are significant in that an additional approach (which may be particularly useful for rapid screening) has been added to our armamentarium for study of biologic effects of various fats.

Butter, Corn Oil and Fibrinolysis in Rats

We have recently reported a dietary method for the production of thrombosis and infarcts in rats and have suggested that part of the mechanism of thrombosis in these animals was interference by the diet with some hematologic factor, possibly fibrinolysis. In the study reported herein, we have developed a method for studying fibrinolysis in rats in vitro, utilizing an electronic device called the Thrombelastograph. Results of this study correlate well with the previously demonstirated thrombogenic properties of 2 of the diets. Rats on a “butter-thiouracil-cholesterol-bile salt” diet (known to produce thrombi and infarcts) have prolonged clotlysis times, as compared with rats on a similar diet (and not thus far associated with thrombi and infarcts) in which corn oil is substituted for butter. Although the in vitro test is performed under highly artificial conditions, they are carefully standardized and the fact that the results correlate well with previously demonstrated thrombogenic properties of the diet would suggest that it has practical value for the study of thrombogenic effects of various diets in experimental animals. It is possible that it will prove to be even more useful in the study of fibrinolysis in man.

Alveolar Walls in Mitral Stenosis

Pathologic alterations of alveolar walls in 95 autopsied patients with mitral stenosis were not frequent. The most frequently encountered change was capillary dilatation, and in 83 per cent of the patients, even this change was slight or absent. Other alterations were focal and involved only small proportions of the area of tissue examined. A generalized increase in the thickness of basement membranes could not be demonstrated.