Manuel R. Malinow

A Model for Therapeutic Interventions on Established Coronary Atherosclerosis in a Nonhuman Primate

The observations so far conducted in cynomologus monkeys on semipurified diets containing butter and cholesterol suggest that this nonhuman primate is an excellent model for studying the therapy of established coronary atherosclerosis. (1) This species is available at a reasonable cost and can be kept in captivity in good health for prolonged periods of time. (2) It readily accepts semipurified diets with a percentage composition similar to that of human diets in the U.S. (3) Ingestion of these diets leads quite rapidly (around 6 months) to moderate coronary atherosclerosis. More prolonged feeding leads to lesions which are histologically very similar to those in man. (4) The distribution of lesions in the main coronary arteries is similar to that in man. (5) Methods to quantify the coronary lesions are available. (6) The diets can be so modified that cholesterol levels closely resemble those in hypercholesterolemic man. (7) The monkeys are amenable to several therapeutic regimens which show promise of arresting the progress or inducing the regression of the coronary lesions.

Cholesterol: treadmill activity accelerates oxidation in rats.

Cholesterol-26-14C was injected intravenously into male and female rats of two different strains. Recovery of radioactivity from the expired air was increased by treadmill activity.

The effects of pyridinolcarbamate on induced atherosclerosis in cynomolgus monkeys (Macaca ira)

Abstract Atherosclerosis was induced in cynomolgus monkeys ( Macaca iya ) fed on a semipurified diet containing 0.5% cholesterol. No differences in the extent of aortic or coronary atherosclerosis were observed when pyridinolcarbamate (2–6 pyridine-dimethanol-bis ( N -methylcarbamate)), was added to the diet at concentrations ranging from 400–2000 mg/kg food.

Muscular activity and the degradation of cholesterol by the liver

Abstract [1, 2 α- 3 H]Cholesterol lipoproteins were injected intravenously into bile-duct cannulated anesthetized rats; cholic [ 14 C]carboxyl acid or radiopaque material was introduced into the small intestine. The animals also received intraenteric infusions of bile with or without whipping cream. Repeated contractions of the skeletal musculature increased the biliary secretion of products from the cyclic portion of the cholesterol molecule and of absorbed [ 14 C]cholic acid without modifying intestinal motility.

A new method for determining liver microsomal cholesterol 7α-hydroxylase

A method is described to determine the mass of 7alpha-hydroxy cholesterol synthetized in vitro by liver microsomes without the use of a radioactive substrate.

The effect of pyridinolcarbamate on aortic and coronary atherosclerosis in squirrel monkeys(Saimiri sciurea)

Summary Adult female squirrel monkeys were given a semisynthetic diet high in butter, sucrose, and cholesterol. The presence of aortic and coronary atherosclerosis was readily observed after a 4-month experimental period and was not modified by previous gonadectomy. Pyridinolcarbamate (2–6 pyridine-dimethanol-bis[N-methyl-carbamate]) together with the atherogenic diet given to intact and spayed monkeys at an approximate dosage of 10–16 mg/kg, proved ineffectual in altering the incidence or severity of the arterial lesions.

Removal of plasma cholesterol by adsorption chromatography.

Batch and column chromatography with porous glass decreased the plasma concentration of cholesterol. Extracorporeal circulation of blood through a column filled with porous glass, as well as exchange transfusion with blood made hypocholesterolemic by passage of its plasma through a column filled with porous glass, temporarily reduced plasma cholesterol concentration in rats.

Experimental myocardial infarction in unanesthetized monkeys

Abstract Experiments were undertaken to study myocardial infarction in non-human primates without the use of anesthetics or sedatives. During surgery, a snare was placed loosely around the left anterior descending coronary artery in 34 rhesus monkeys ( Macaca mulatta ). Several days later, myocardial infarction was studied from the moment it was induced. The technique was reproducible and the distribution of necrosis was fairly constant. Aortic flow, aortic blood pressure, left atrial pressure, and the ECG were monitored. A computer program for discriminant analysis, based on data obtained within 30 minutes after infarction, resulted in retrospective predictions of 100 per cent in animals dying from cardiogenic shock and in predictions of 93 per cent in surviving animals.

Spontaneous Bundle Branch Block in Rhesus Monkeys

Naturally occurring ventricular conduction abnormalities are described in 23 rhesus monkeys and compared with findings in 15 control animals. Electrocardiograms and Frank vectorcardiograms were recorded and ventricular endocardial leads were obtained in four of the animals. Three examples of left bundle branch block and five of right bundle branch block were found. Less marked degrees of abnormal intraventricular conduction are described in 15 others.

Absorption of cholesterol and β-sitosterol from cigarette smoke in Macaca mulatta☆

When smoke from single cigarettes containing [4-14C]cholesterol or beta-[4-14C]sitosterol was delivered to the lungs of Rhesus macaques, plasma contained radiolabeled sterols up to 50 days later. Since cholesterol, as well as plant sterols (campesterol, stigmasterol and beta-sitosterol), are normally present in cigarette smoke, our observations suggest that protracted absorption of sterols occurs after cigarette smoking.