Circulatory effects of diazepam in heart disease

Diazepam was administered to ten patients with heart disease during diagnostic cardiac catheterization, in order to determine whether or not this drug's circulatory actions could alter results obtained during the procedure. Diazepam produced no change in baroreceptor sensitivity; however, there was a significant rise in heart rate and a significant fall in aortic systolic and left ventricular end-diastolic pressures. Cardiac index was unchanged, whereas stroke volume fell significantly. Systemic vascular resistance and peak left ventricular dp/dt did not change throughout the study. Clinical response in terms of sedation was judged to be satisfactory in eight patients, and no adverse effect on respiration was noted. Diazepam has little effect on basal circulatory and respiratory parameters when changes in these parameters are averaged for our ten patients. However, substantial changes in hemodynamic parameters did occur in several individuals, and such alteration in circulatory function must be considered when this agent is used routinely in patients having diagnostic cardiac catheterization.     

AUTOGRP: an interactive computer system for the analysis of health care data

AUTOGRP is an interactive computer system designed to facilitate rapid analysis of complex medical information. AUTOGRP allows the clinical or administrative expertise of the user to be combined with sophisticated computer techniques to permit rapid information retrieval, hypothesis testing, development of norms, and identification of deviant cases. This interaction yields results of a uniquely high statistical and medical quality. AUTOGRP has been used to aid in understanding the process of patient care management in a variety of settings in order to enhance the effectiveness of decision-making from both a medical and management point of view.     

The isolated supported canine heart: a model for the evaluation of drug effects on regional myocardial blood flow

The present investigation was designed to determine the effect of propranolol on regional myocardial blood flow and oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. The transmural distribution of blood flow, determined by the radioactive microsphere technique, was expressed as the epicardial/endocardial blood flow ratio (epi/endo). Propranolol (0.5 mg/kg i.v.) produced a significant decrease in heart rate and myocardial contractile force and an increase in coronary artery perfusion pressure due to an increase in coronary vascular resistance. These hemodynamic changes were accompanied by significant decreases in epi/endo (increased endocardial perfusion) and MVO2. Reduction of perfusion pressure to control by a decrease in total coronary blood flow produced no further change in epi/endo or MVO2. However, increasing heart rate to control increased epi/endo to predrug levels. Contractile force and MVO2 remained reduced below control. Norepinephrine infusion (1 mug/min intracoronary) produced a significant increase in heart rate and contractile force and decrease in perfusion pressure. These changes were accompanied by an increase in epi/endo and MVO2. Propranolol (0.5 mg/kg i.v.) abolished the response to norepinephrine. Propranolol may produce beneficial effects in angina pectoris by a decrease in epi/endo (via a reduction in heart rate) and MVO2 and by beta adrenergic blockade of the deleterious effects of catecholamines.     

Left ventricular function by echocardiography in children with fixed aortic stenosis

Left ventricular function was evaluated echocardiographically within 24 hours of cardiac catheterization in 45 children with fixed aortic stenosis. Left ventricular systolic time intervals, mean velocity of circumferential fiber shortening, left ventricular end-diastolic volume and shortening fraction were evaluated. Some patients with severe aortic stenosis had a shortened preejection period, prolonged ejection time and increased mean velocity of circumferential fiber shortening in comparison with normal subjects, but these findings were not consistent within the group with severe aortic stenosis or apparent in patients with mild or moderate aortic stenosis. Left ventricular end-diastolic volume was smaller in children with severe obstruction than in normal children. Evaluation of the shortening fraction provided good separation of patients with significant obstruction from those with mild disease. Further, there was a linear correlation between the shortening fraction and the left ventricular-aortic gradient demonstrated at cardiac catheterization. This correlation was also of use in evaluating the response of patients to surgical relief of obstruction. Pre- and postoperative echocardiographic evaluation of the shortening fraction appears to provide a readily available noninvasive method of assessing the course and severity of obstruction in fixed aortic stenosis in children.     

Circadian rhythms of serum renin activity and serum corticosterone, prolactin, and aldosterone concentrations in the male rat on normal and low-sodium diets

To investigate the control of aldosterone secretion, non-stress levels of serum aldosterone, corticosterone, and prolactin, and renin activity were determined at 4-h intervals during 24-h light-dark cycles in adult male rats on regular and low-sodium diets. Circadian rhythms of plasma aldosterone, prolactin, and corticosterone concentrations and of serum renin activity were demonstrated during a regular sodium diet. When the rats were on a low-sodium diet, a circadian rhythm of serum corticosterone and aldosterone concentration was observed, but there was no circadian variation in serum renin activity or in serum prolactin concentration. Serum aldosterone concentration correlated with serum corticosterone concentration (r = 0.48) and serum renin activity (r = 0.36) during a low-sodium diet. Serum prolactin concentration did not correlate with serum aldosterone concentration or serum osmolality. These data are compatible with a role for renin and ACTH, but not for prolactin, in the modulation of aldosterone secretion in the rat.     

Enhanced toxicity for mice of combinations of bacterial lipopolysaccharide and vincristine

Sublethal doses of vincristine (VNC) and bacterial lipopolysaccharide (LPS) administered simultaneously to adult male mice resulted in markedly enhanced mortality. All of 10 strains of Pseudomonas aeruginosa tested, 4 of 7 strains of Bacteroides, and 6 of 10 strains of Listeria monocytogenes were able to substitute for purified LPS in enhancing mortality in VNC-treated mice. Inoculation of mice with each of 10 strains of Pseudomonas, each of 7 strains of Bacteroides, and about half of the 10 strains of Listeria tested elicited increased resistance to the lethal action of purified LPS. The patterns of responses of mice receiving a lethal combination of 2 mg of LPS/kg and 1 mg of VNC/kg resembled those of mice receiving a lethal dose of 10 mg of VNC/kg alone or 15 mg of LPS/kg alone with respect to (i) serum glutamic pyruvate transaminase activity, (ii) hematocrit values, and (iii) thrombocytopenia. The patterns of responses of mice receiving a lethal combination of LPS and VNC resembled those of mice receiving a lethal dose of LPS alone with respect to (i) hypothermia, (ii) retention of sulfobromophthalein, (iii) fibrinogen level, (iv) prothrombin activity, (v) blood urea nitrogen levels, and (vi) time of death. These data are consistent with the proposition that the combination of VNC and LPS produces a fatal renal failure. Histological studies confirmed that there was extensive renal damage in mice treated with lethal doses of LPS alone or a lethal combination of LPS and VNC.