Harold L. Rutenberg

Measurement of the initial rate of serum cholesterol esterification

Abstract A method for the measurement of initial rate of serum cholesterol esterification is described. The technique is a modified version of the assay described originally by Stokke and Norum (7). Improvements include the depression of background values as well as an increase in the overall efficiency of the procedure. The study of healthy male human subjects revealed that the initial rate of cholesterol esterification increases linearly with the individuals serum free cholesterol content.

Serum cholesterol esterification in species resistant and susceptible to atherosclerosis

Abstract Initial rates of cholesterol esterification were measured in rat, rabbit, pig, dog, guinea pig and human serum. The data indicate a tendency for the rate of esterification to increase with serum free cholesterol levels in all species. The fractional rate of esterification ( % cholesterol esterified/min) for the species in decreasing order are rat, guinea pig, rabbit, dog, pig and man.

Alterations of Cardiac Sympathetic Neurotransmitter Activity in Congestive Heart Failure

The sympathetic nervous system exerts an important direct effect on cardiac function which is mediated by the release at the terminal sympathetic nerve endings of the neurotransmitter norepinephrine. These nerve terminals are complex structures involved in synthesis, uptake, binding and storage as well as release of norepinephrine. The evidence for alteration of many of these functions in congestive heart failure, which is characterized by a depletion of myocardial norepinephrine stores, is reviewed. Although cardiac norepinephrine depletion alone is not responsible for the intrinsic depression of cardiac contractility in failing heart muscle, this depletion probably removes a potentially important compensatory mechanism for augmenting myocardial force development and velocity of contraction in the failing heart. Evidence for parasympathetic-sympathetic system interactions as they affect the heart, as well as alterations in the parasympathetic nervous system in heart failure, is also presented briefly.

Studies on Enzymatic and Molecular Properties of Lecithin: Cholesterol Acyltransferase

I. Cholesterol esterification in human serum was measured in healthy male and female subjects using a modified version (2) of the Stokke & Norum assay technique (1). Strong positive correlation was observed between the rate of cholesterol esterification and serum free cholesterol esterification (rp = 93, p < 0.001 for males: rp = 81, p < 0.001 for females), suggesting that the fractional rate of esterification is a more useful parameter for comparative studies than the rate of esterification.II. Purification and characterization of LCAT. Highly purified LCAT preparations were obtained by using the combined techniques of density gradient centrifugation, DEAE cellulose chromatography, and affinity chromatography. A stable 4000-fold purified preparation was obtained as the result of this procedure, yielding 2 bands on acrylamide gel electrophoresis in the presence or absence of sodium dodecyl sulfate (SDS). Molecular weight determinations on calibrated gel columns give a value of 95, 000 in the absence and a...

On the rate of cholesterol esterification in cord blood serum.

Cholesterol esterification was studied in adult and cord serum by measureing the initial rate of lecithin-cholesterol acyl transferase (LCAT) activity. Cord serum had about one-third as much free and esterified cholesterol and about one-half as much LCAT as adult serum. When the adult LCAT activities are plotted against the individuals serum free cholesterol levels a straight line relationship results (0.101±.005% cholesterol esterified per min). Cord serum LCAT activities (.135±.0407% cholesterol esterified per min) in the main fall above the adult line. Our results show that cord serum can esterify cholesterol at a rate equal to or higher than adult serum when the LCAT activity is related to the amount of serum free cholesterol present.

Inhibition of lecithin:Cholesterol acyltransferase following intravenous administration of heparin in man

Abstract 1. 1. Lecithin:cholesterol acyltransferase (EC 2.3.1.43) is the enzyme responsible for the esterification of free cholesterol in human plasma. A marked decrease in the initial rate of enzyme activity was observed in the sera of subjects who received 5000 units of heparin intravenously 4 h after a 1200 calorie meal. This inhibition occurred coincident in time with a marked elevation of serum free fatty acid concentration. Both of these effects could be observed as early as I min following heparin administration. 2. 2. When heparin was given to subjects in the fasting state, the inhibition of enzyme activity was seen only in subjects whose serum triglyceride levels were sufficiently high to produce free fatty acid concentrations in excess of 1000 μequiv/1. 3. 3. In vitro addition of free fatty acids (in the form of palmitic acid) and lysolecithin to the reaction mix separately and together also resulted in reduced enzyme activity which could in turn be reversed by increasing amounts of serum albumin. The data are consistent with the presence of multiple sites for the binding of free fatty acids and lysolecithin by serum albumin: One site binds up to 2 moles of free fatty acids per mole of albumin. The excess free fatty acids compete with lysolecithin for a second site, the binding capacity of the lysolecithin being approx. I mole of lysolecithin per mole of serum albumin. Thus, lecithin:cholesterol acyltransferase inhibition may be caused by a combination of elevated free fatty acids and unbound lysolecithin, the latter being a product of the lecithin:cholesterol acyltransferase reaction which apparently cannot be removed from the enzyme surface when free fatty acids already occupy lysolecithin binding sites on serum albumin.

Simulation of "left atrial rhythm" by right atrial pacing.

Abstract In a patient with electrocardiographic criteria for the diagnosis of socalled left atrial rhythm, a similar pattern was produced by catheter pacemaker stimulation of the wall of the mid-right atrium, low right atrium and coronary sinus. These findings are presented as evidence for the need of increased caution before assuming that a left to right pattern of atrial depolarization, as interpreted in leads I, V 1 and V 6 of the scalar electrocardiogram, can pinpoint the anatomic origin of the pacemaker.

Asymptomatic rapid ectopic tachycardia induced by and persisting during prolonged exertion.

Abstract A case is reported of a 39 year old healthy man who has a prolonged and unusual tachycardia, probably ventricular or atrioventricular junctional with aberration, with a rate of 214/min, during strenuous exertion in the upright position. This arrhythmia occurs whenever the exertion produced is vigorous enough to evoke a sinus tachycardia of 180/min and persists until the exertion is decreased and the sinus rate decreases below 180/min. The patient is free of cardiac symptoms both at rest and while running several miles daily during which time the unusual tachycardia is almost constantly present. There are no significant S-T segment changes during or after exercise.

In vitro serum cholesterol esterification in coronary artery disease

The mean serum in vitro cholesterol esterification as determined by the decrease in the concentration of free cholesterol after incubation of serum for 3, 6, 24, and 48 hours has been compared in four groups: subjects with acute myocardial infarction, subjects with chronic coronary artery disease, age-matched healthy controls, and young healthy controls. The original data revealed a significantly decreased esterification in subjects with chronic coronary artery disease compared to the group of age-matched controls (p < 0.05), and a significantly increased free cholesterol in subjects with acute myocardial infarction compared to the age-matched healthy subjects (p < 0.05). Comparisons of these four groups were then made by removal of those subjects with total cholesterol > 300 mg. per 100 ml. and 300 mg. per 100 ml. When the statistical analysis was performed, the mean in vitro cholesterol esterification was significantly decreased at 6 hours (p < 0.02), 24 hours, and 48 hours (p < 0.01 in) subjects with chronic coronary artery disease compared to age-matched controls and was significantly decreased at 6 hours (p < 0.05) and 48 hours (p < 0.01) in subjects with acute myocardial infarction compared to the age-matched controls. The average slope describing cholesterol esterification over time was significantly decreased in acute myocardial infarction and chronic coronary artery disease (p < 0.01). On the other hand, there were no significant differences between the young healthy group and the older age-matched healthy subjects. Although these findings suggest the possibility that subjects with coronary artery disease have a deficiency of lecithin: cholesterol acyltransferase, the limitations of this study are stressed. It is unlikely that a firm conclusion will be available until an accurate method of determining the initial rate of plasma cholesterol esterification is available and until the enzyme is purified.

On the electrocardiogram and clinical improvement after myocardial aneurysmectomy

Abstract A case is reported to show that removal of a huge ventricular aneurysm does not necessarily lower resting left ventricular end-diastolic pressure and that reduction of elevated left ventricular end-diastolic pressure is not essential for clinical improvement to occur after myocardial aneurysmectomy. Some possible causes of clinical improvement are discussed. It is suggested that clinical improvement after operation in the patient reported might be due to saving of energy required to move the akinetic mass of aneurysm and to a more normal and therefore more effective ventricular contraction, and that the latter is reflected in the tendency towards normalization of the ECG after operation.