Samuel Proger

Studies of Coagulation and Fibrinolysis of the Arterial and Venous Blood in Normal Subjects and Patients with Atherosclerosis

In studies of coagulation of the arterial and venous blood of relatively young normal subjects, there were statistically significant arteriovenous differences in some of the tests employed. These differences, however, were not all in the same direction, in that some indicated increased and some decreased coagulation activity of the arterial blood. In patients with coronary heart disease, these arteriovenous differences were absent or less marked. It was suggested that this change in arteriovenous difference in such patients could possibly be attributed to the surface effect of the diseased arterial wall on the coagulation mechanism. It was recognized, however, that a number of other factors could contribute to, or entirely account for, this phenomenon.There was some evidence of increased coagulation activity in the venous blood of patients with coronary heart disease as compared to matched controls. This was indicated by a more rapid generation of thromboplastin with the addition of inosithin (platelet substitute), and a more rapid generation as well as a greater yield of thromboplastin without the addition of inosithin.Fibrinolytic activity was significantly lower in the arterial blood compared to the venous in both the normal subjects and patients with atherosclerosis. This arteriovenous difference was greater in the atherosclerotic group and it was widely variable. Because of this variability, venous fibrinolysis determinations could not be taken as an indicator of the level of fibrinolytic activity in the arterial blood. Hence, it was suggested that in studies of fibrinolysis as related to atherosclerosis, arterial blood samples should be routinely used.Fibrinolytic activity of the blood in the atherosclerotic group as a whole was lower than that in the normal group on both the arterial and the venous sides. The difference between the two groups was greater in the arterial than the venous blood. In the group with atherosclerosis, the subgroup with coronary heart disease and that with occlusive disease of the peripheral arteries were separately analyzed. The subgroup with coronary heart disease exhibited a significantly lower fibrinolytic activity compared to normal subjects only in the arterial blood, whereas the subgroup with occlusive disease of the peripheral arteries showed a lower fibrinolytic activity in both the arterial and the venous blood. In the subgroup with occlusive disease of the peripheral arteries, it was particularly note-worthy that the younger patients had a very low fibrinolytic activity. It was thought that one could only speculate as to whether this low fibrinolytic activity in such young patients is in any way causally related to the disease process.It appeared that in patients with coronary heart disease the delicate balance of coagulation and fibrinolysis was tipped in the direction of clot formation. It was not clear, however, whether the changes in blood coagulation and fibrinolysis observed in such patients were etiologic in the pathogenesis of the disease process, associated with it, or simply a secondary phenomenon. Moreover, it was recognized that in vitro demonstration of such changes in blood coagulation and fibrinolysis does not necessarily imply in vivo hypercoagulability.No correlation was found between the level of serum cholesterol and plasma fibrinolytic activity.

The effects of the ingestion of excessive amounts of sodium chloride and water on patients with heart disease

Abstract 1. 1. In patients who are recovering from heart failure, a moderate increase in the ingestion of sodium chloride may produce, within four to eight days, a clinical picture which is indistinguishable from that of congestive heart failure. Such an effect is obviated by digitalization. 2. 2. Under similar conditions, an increase to 3,000 c.c. in the daily intake of water for as long as eight days results in no measurable or noticeable harmful effects. 3. 3. The harmful effects of an increase in the intake of sodium chloride are apparently related to the degree of sodium retention, rather than the increased intake as such. 4. 4. The possible mechanism of sodium retention is discussed. 5. 5. It is suggested that, since there is a significant degree of sodium retention during upper respiratory infections, the latter may play a role in the oft-observed relationship between infection and the precipitation or aggravation of heart failure.

Studies of Blood Coagulation and Fibrinolysis in Patients with Idiopathic Hyperlipemia and Primary Hypercholesteremia before and after a Fatty Meal

In view of the current interest in the possible relationship between elevated serum lipid levels, increased coagulability of the blood (or decreased blood fibrinolysis) and ischemic heart disease, the clotting and fibrinolytic activity of the blood were studied before and after a fatty meal in 9 patients with idiopathic hyperlipemia, 10 patients with primary hypercholesteremia, and 10 normal subjects. Six patients had evidence of coronary heart disease. The methods of study included procedures designed to assess the over-all coagulability of the blood as well as the measurement of specific clotting factors. Blood fibrinolytic activity was measured by both direct and indirect methods. Serum lipid studies were performed simultaneously.

Some effects of injected cytochrome C in myocardialand cerebral anoxia in man

Summary 1. The effects of anoxia on the electrocardiogram can be prevented by theinjection of cytochrome C. 2. Subjects seem to tolerate anoxia more easily when they have been previously injected with cytochrome C. 3. The effects of anoxia in impairing visual discrimination can be overcomeby the intravenous injection of cytochrome C. 4. The effects of anoxia in slowing the cerebral functions required for code transliteration can be overcome by the injection of cytochrome C.

Plasma Cephalins of Patients with Acute Myocardial Infarction

In the plasma of patients with acute myocardial infarction the values for phosphatidyl ethanolamine are on the average 50% to 100% higher than in patients with chronic coronary heart disease and up to 400% higher than in normal individuals. Those for phosphatidyl serine are about 50% higher than in patients with chronic coronary heart disease and up to 300% higher than in normal individuals. Expressed in percentages of total phospholipids, the share of phosphatidyl ethanolamine in acute myocardial infarction is about twice as high as in chronic coronary heart disease and three times as high as in healthy persons. The share of phosphatidyl serine is about 50% higher than in patients with chronic coronary heart disease and also almost 300% higher than in healthy persons. Following the acute incident the values for the cephalins, both phosphatidyl ethanolamine and phosphatidyl serine, decrease slowly. Phosphatidyl ethanolamine reaches the level found in patients with chronic coronary heart disease in about 4 weeks, phosphatidyl serine in about 1 week.

A career in ambulatory medicine.

To meet the need and resolve long standing conflicts in the delivery of primary care in an age of specialization, I propose an experiment with a different type of primary medical education based on the separation of careers into community-oriented primary and continuing care of ambulatory patients and hospital-based intensive care of acutely ill bed patients. High-school graduates selected for interest, aptitude, and personality would follow a six-year pathway through college and medical school. A singular feature of the proposal would be the replacement of bedside training with an undergraduate traineeship of two to 2 1/2 years in the hospital ambulatory specialty clinics, emergency clinic, and a primary-care model practice unit, followed by a one-year externship in this primary-care center. The graduate would be oriented toward group and team practice and would work in a system integrating primary, secondary, and tertiary care.

Antihypertensive Drugs: Praise and Restraint

Edward D. Freis was a happy choice for the Albert Lasker Award for Clinical Research. He received the Award for directing the Veterans Administration Cooperative Study Group on Antihypertensive Age...

Effect of a Combination of Propranolol and Nicotinic Acid on the Inhibition of Norepinephrine-induced Elevations of Serum Triglyceride, Serum Glycerol, and Plasma Free Fatty Acids in the Dog

Abstract A study was made of methods to reduce the concentration of serum triglyceride by suppressing plasma free fatty acid mobilization through a dual modification of their release mechanism. Serum triglyceride, serum glycerol, serum cholesterol and plasma free fatty acids were measured under the influence of infusions of norepinephrine and low doses of propranolol and nicotinic acid in dogs. During a 4 hr infusion of norepinephrine, serum triglyceride rose 20 per cent. The addition of individual infusions of low doses of propranolol and nicotinic acid had a small effect. However, the infusion of low doses of these two agents in combination had an additive effect, causing serum triglyceride to fall 25 per cent. A similar inhibitory effect of propranolol and nicotinic acid used in combination was noted in a sustained reversal of norepinephrine-induced elevations of serum glycerol and plasma free fatty acids. Serum cholesterol was not changed over the 4-hour period by any agent as compared to saline. The effects of small doses of propranolol and nicotinic acid used in combination on the inhibition of norepinephrine-induced elevations of serum triglyceride may be explained by their additive inhibition of plasma free fatty acid mobilization.

Synergistic Effect of Propranolol and Nicotinic Acid on the Inhibition of Plasma Free Fatty Acid Release in the Dog

Fatty acid mobilization was effected in 24 anesthetized dogs by infusion of norepinephrine over a four-hour period. Infusions of propranolol and nicotinic acid at various doses, individually and in combination, were added and free fatty acid levels were serially determined. Synergistic action of the two agents was apparent in that minimally effective concentrations of the two agents when used in combination suppressed the release of free fatty acids to 29 percent of levels achieved with norepinephrine (1,186 μEq/L). and 70 percent of levels in saline control animals (501 μEq/L). Large individual doses were no more effective than low doses used in combination. The synergistic action of propranolol and nicotinic acid in the suppression of free fatty acid mobilization may be explained by the action of these two agents on the inhibition of the adenyl cyclase system of the adipose tissue cell. This synergistic action in reducing plasma free fatty acids and their effect on lipid synthesis would allow the use of smaller doses that could reduce the risk of side effects.

Atherogenesis and thrombogenesis in the rat.

Summary and conclusions Three groups of rats were given diets containing cholesterol, sodium cholate and propylthiouracil. In addition the diets contained a fat that consisted of 40% butter in Group I, 40% corn oil in Group II and 8% corn oil in Group III. All groups showed atheromatous lesions and thrombus-like masses in cardiac chambers and in great vessels. Infarcts were present in a small number of animals in each group. Incidence and severity of atheromatous lesions varied but this variation was mainly related to length of survival on the diet rather than the type of added fat. There was no isolated development of thrombosis related to the type of fat in the diet as suggested by some investigators. Moreover, reservations were expressed regarding the exact nature of the thrombus-like masses and infarcts and their relevance to atherosclerosis, thrombosis, and infarction in man.