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Biomedical subjects

E R Smith

Publications and source records attributed to E R Smith.

At least 127 records · Page 7Linked to original sources
PubMed1992

The importance of pericardial constraint in experimental pulmonary embolism and volume loading.

To clarify the magnitude of the contribution of pericardial constraint to the hemodynamic deterioration that is observed during acute pulmonary embolism, hemodynamics and chamber dimensions (sonomicrometry) were measured during pulmonary embolization and subsequent volume loading in six anesthetized and instrumented open-chest, open-pericardium dogs. Embolization markedly increased peak right ventricular systolic pressure (38 +/- 5 mm Hg before embolism to 64 +/- 12 mm Hg after repeated embolization, p less than 0.05). However, right ventricular stroke volume decreased by only an insignificant amount (17 +/- 7 ml to 15 +/- 6 ml, p = not significant). Indices of left ventricular end-diastolic volume (left ventricular area = anteroposterior x septum-to-left ventricle free wall diameters) and stroke work (stroke work = area of the left ventricular pressure-area loop) were also similar before and after repeated embolization. Volume loading after repeated embolization resulted in increased right ventricular stroke volume (15 +/- 6 ml to 20 +/- 4 ml, p = 0.06), left ventricular area (3320 +/- 600 mm2 to 3470 +/- 580 mm2, p less than 0.05) and stroke work (261 +/- 158 mm Hg to 425 +/- 170 mm Hg x mm2, p less than 0.05). These results are in marked contrast to those in a previously reported study in a closed-chest and closed-pericardium model in which there was a decrease in left ventricular preload and systolic function after similar embolization-induced right ventricular pressure loading. Moreover, there was a further decrease in these parameters as a result of volume loading after embolism in the closed pericardium experiments. In conclusion, pericardial constraint contributes to hemodynamic deterioration during both acute right ventricular pressure loading and subsequent volume loading. The hemodynamic response to both interventions in the intact animal is determined not only by the degree of right ventricular dysfunction but also by the degree of direct ventricular interaction.

Animals↗
PubMed1992

The right and left ventricular intracavitary and transmural pressure-strain relationships.

The magnitude of pericardial pressure and therefore the shape of the right ventricular end-diastolic transmural pressure-volume relationship remains controversial. To investigate ventricular compliance, eight dogs anesthetized with fentanyl were instrumented as follows. Right and left ventricular intracavitary pressures were measured with micromanometer-tipped catheters. Right and left ventricular free wall segment lengths were measured by sonomicrometry. Pericardial pressure was measured over the right and left ventricles by means of flat liquid-containing balloon transducers, and transmural pressures were calculated as the difference between intracavitary and pericardial pressures. After defining the pressure-segment length relationship by vena caval constriction followed by release and blood transfusion, the pericardium and chest were opened widely and the cardiac volume manipulation was repeated; this allowed direct measurement of transmural right ventricular end-diastolic pressure for each level of strain recorded with the chest and pericardium closed. When intracavitary right or left ventricular end-diastolic pressure was raised from zero to 20 mm Hg, the respective transmural pressures increased from 0.2 +/- 0.6 (SD) mm Hg to 2.5 +/- 1.8 mm Hg and from 0.3 +/- 0.7 mm Hg to 6.0 +/- 2.5 mm Hg. Ventricular segmental strain increased by 7.0 +/- 0.8% and 6.0 +/- 0.2%, respectively. No statistically significant differences were found between right ventricular calculated (intracavitary minus pericardial pressure) and measured (open pericardium, open chest) transmural pressures at a given strain, thereby confirming the accuracy of our pericardial pressure measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Increased bioactive luteinizing hormone levels in postmenopausal women with endometrial cancer.

OBJECTIVE: The purpose of our study was to investigate the secretion of immunoactive and bioactive luteinizing hormone in postmenopausal women with endometrial cancer. STUDY DESIGN: Seventeen postmenopausal women with endometrial cancer and nine without cancer were studied. Blood samples were collected at 15-minute intervals for 360 minutes. All samples were assayed for bioactive luteinizing hormone by rat interstitial cell testosterone assay and for immunoactive luteinizing hormone by radioimmunoassay. Serum pooled from 6-hour sampling was assayed for follicle-stimulating hormone, total estradiol, unbound estradiol, and estrone. RESULTS: Patients with endometrial cancer had significantly (p < 0.01) higher bioactive luteinizing hormone levels (mean +/- SE 276 +/- 26 IU/L) as compared with those of control women (144 +/- 18 IU/L). Bioactive/immunoactive ratios of luteinizing hormone were significantly higher (p < 0.01) in women with cancer (5.8 +/- 0.7) than in those without cancer (2.5 +/- 0.5). There was a significant (p < 0.001) positive correlation (r = 0.582) between unbound estradiol levels and bioactive luteinizing hormone concentrations. CONCLUSIONS: There is an increase in bioactive luteinizing hormone secretion in postmenopausal women with endometrial cancer. This could lead to an increase in ovarian androgen production resulting in increased prehormone availability for estrogen formation from peripheral conversion.

Aged↗
PubMed1992

Hormones and sexual behavior in relationship to aging in male rats.

To determine if the age-related decline in male sex behavior is correlated with hormonal factors, a longitudinal study was conducted. Sexually experienced males were given mating tests every 2 months from 7 through 27 months of age. To study possible relationships between changes in behavior and alterations in hormone levels, blood samples were taken before and after these bimonthly tests. At 23 months, cross-sectional studies were also conducted comparing results to those obtained in 5-month-old males. Significant changes in mating behavior first appeared at 11 months; mount latency, intromission latency, ejaculation latency, postejaculatory interval, and intercopulatory interval were increased. Similarly, detectable decreases in testosterone (T) also occurred at this age. A significant decline in luteinizing hormone (LH) was not seen until 19 months. Correlational analyses revealed small (r less than or equal to -0.29) but significant negative correlations between T and parameters of mating behavior with age. When each age was examined separately, no significant correlations appeared. Plasma T was not predictive of behavioral performance. At 23 months, cross-sectional studies revealed deficits in mounting and penile reflex behavior but ejaculatory reflex capacity was unimpaired. At 28 months, males were decapitated. Only T levels showed a significant effect of age; estradiol, prolactin, and LH were unaffected when compared to 5-month-old males. The data suggest that although there are small and significant negative correlations between circulating testosterone and parameters of mating behavior with advancing age, it is unlikely that the observed decline in testosterone is the primary cause of the age-induced behavioral deficits. It is likely that the major causal factor(s) involves non-hormone-dependent changes within the CNS.

Aging↗
PubMed1992

Uterotropic action in rats of amsonic acid and three of its synthetic precursors.

Prompted by reports of sexual impotence among chemical factory workers exposed to amsonic acid (4,4'-diaminostilbene-2,2'-disulfonic acid; CAS 81-11-8) and its synthetic precursors 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNSDSA; CAS 128-42-7), 2-methyl-5-nitrobenzenesulfonic acid (MNBSA; CAS 121-03-09), and 4-nitrotoluene (CAS 99-99-0), the uterine-weight-increasing actions of single intraperitoneal doses of these chemicals were determined at 24 h after treatment in weanling female rats and compared to the results of similar experiments with diethylstilbestrol (DES; CAS 56-53-01), a synthetic estrogen chemically related to amsonic acid and DNSDSA. Doses of 100 mg/kg or less of amsonic acid were either without effects or produced equivocal effects, while uterine weights were increased after doses of 300 and 1000 mg/kg; doses of 3000 mg/kg were clearly toxic. Neither DNSDSA nor MNBSA increased uterine weight after doses that were not overtly toxic. Doses of 10 mg/kg or less of 4-nitrotoluene were without effect, but doses of 30 and 100 mg/kg increased uterine weights without producing overt toxicity; doses of 1000 mg/kg were clearly toxic. While both amsonic acid and 4-nitrotoluene exhibited uterotropic effects, they were both much weaker than DES in this respect. Other experiments indicated that the time course of the effects of approximately equiactive doses of amsonic acid and DES were very similar, and that the responses to oral doses of amsonic acid were not appreciably different from the responses to the same doses given intraperitoneally. Finally, a sample of amsonic acid taken from the workplace of the complaining workers was also found to have uterotropic activity. These experiments suggest that amsonic acid and 4-nitrotoluene have estrogenic activity, and thus provide a possible mechanistic explanation for the complaints of impotency in factory workers exposed to these substances.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1992

Relation between nocturnal melatonin profile and hormonal markers of puberty in humans.

We examined the relation between nocturnal melatonin and hormonal markers of puberty in 57 normal children and adolescents and 39 subjects with disorders of pubertal onset. Melatonin was measured in hourly blood samples drawn overnight by constant withdrawal. Basal 08.00 h plasma testosterone, estradiol and LH, and the peak LH response to LHRH administration were determined. There were no significant correlations between testosterone, estradiol, basal LH and peak LH and melatonin peak (r = -0.18, -0.22, -0.02, -0.12, respectively) or melatonin peak time (r = 0.12, -0.01, -0.02, 0.07 respectively). The results were not affected significantly by sex, diagnosis or age. A comparison of subjects grouped by peak LH < 15 U/l (most likely prepubertal; n = 40) and peak LH > 30 U/l (most likely pubertal; n = 34) showed no significant differences in melatonin peak (160.5 +/- 59.3 vs. 146.6 +/- 50.9 pg/ml; t = 1.09; p > 0.05) or melatonin peak time (1.8 +/- 1.7 vs. 2.5 +/- 1.7 h; t = -1.79; p > 0.05). Although a pineal-puberty relation cannot be excluded, the results do not support the hypothesis that melatonin restrains the hypothalamic-pituitary-gonadal axis during childhood.

Adolescent↗
PubMed1992

Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy.

BACKGROUND: Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined. METHODS AND RESULTS: Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03). CONCLUSIONS: QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.

Anti-Arrhythmia Agents↗
PubMed1992

Changes in the radius of curvature of the ventricular septum at end diastole during pulmonary arterial and aortic constrictions in the dog.

BACKGROUND: At end diastole, the position and shape of the ventricular septum depend on the transseptal pressure gradient. It is not clear, however, how the septal radius of curvature changes in response to the gradual change in transseptal pressure gradient during progressive pulmonary arterial constriction (PAC) and aortic constriction (AC). METHODS AND RESULTS: In 11 anesthetized open-chest dogs, the septal radius of curvature was measured from the short-axis two-dimensional echocardiogram, and the transseptal pressure gradient (left ventricular [LV] pressure minus right ventricular [RV] pressure) was calculated from ventricular pressures measured with micromanometers. Seven dogs were studied with both PAC and AC (group 1) and four dogs only with PAC, which was initiated before and after volume loading (group 2). The transseptal pressure gradient decreased during PAC. As the transseptal pressure gradient decreased, the septum shifted continuously leftward with decreases in the LV septum-free wall diameter and in LV cross-sectional area. The septal radius of curvature (Rs) increased until the septum became flat. The flat septum (i.e., Rs = infinity) occurred at a relatively constant value of transseptal pressure gradient (-4.6 +/- 1.4 mm Hg) independently of the absolute values of LV pressures when between 2 and 9 mm Hg, although necessarily a greater RV pressure was needed to make the septum flat when LV pressure was higher. After inversion, the septum again became curved, with a decrease in the absolute value of septal radius of curvature as the transseptal pressure gradient became increasingly negative. The septum was still concave to the LV cavity at zero transseptal pressure gradient, and its curvature decreased (i.e., its radius of curvature increased) with increases in ventricular pressures. During AC, the septal radius of curvature also increased, but with an increase in transseptal pressure gradient accompanied by increases in LV septum-free wall diameter and in LV area. In group 2 animals, at zero transseptal pressure gradient, the normalized septal radius of curvature was greater (p less than 0.005) at high LV pressure than at low LV pressure. The transseptal pressure gradient required to make the septum flat was not significantly different between low and high LV pressure, which confirmed the results of group 1. CONCLUSIONS: The results of the present study show that the shape and position of the ventricular septum are determined by the transseptal pressure gradient but that the shape of the septum is also affected by the ventricular pressures. The septum was not flat but rather still concave to the LV cavity at zero transseptal pressure gradient. Approximately 5 mm Hg of negative transseptal pressure gradient was required to displace the septum farther leftward and make it flat. The septal radius of curvature increased during both PAC (which decreased transseptal pressure gradient) and AC (which increased transseptal pressure gradient), indicating that the mechanisms involved in changing septal radius of curvature are different during PAC and AC.

Animals↗
PubMed1992

Rescue angioplasty during myocardial infarction has a beneficial effect on mortality: a tenable hypothesis.

HYPOTHESIS: Rescue percutaneous transluminal coronary angioplasty (PTCA) reduces mortality during myocardial infarction. OBJECTIVE: To determine if PTCA after failed thrombolytic therapy results in reduced mortality. DESIGN: Twenty-eight patients with a persistently occluded infarct artery following thrombolytic therapy more than 3 h after symptom onset were randomized to rescue PTCA (n = 16) or conservative treatment (n = 12) as part of a prospective randomized trial of reperfusion therapy during myocardial infarction in 184 patients. Hospital mortality was assessed in these groups as well as in the 177 patients with known infarct artery status after initial attempts at reperfusion. MAIN RESULTS: There was one death among the 16 patients in the rescue PTCA group versus four deaths in the 12 patients treated conservatively (P = 0.13). Moreover, the death in the rescue PTCA group occurred in one of three patients in whom the procedure failed. Mortality in the entire study group was 10.3% (19 of 184); 4.2% (six of 142) in patients in whom patency was achieved after thrombolysis and/or PTCA and 34.3% (12 of 35) in those in whom reperfusion was not achieved (P less than 0.001). In patients with anterior myocardial infarction, mortality was 6.7% (four of 60) in those with reperfusion and 47.1% (eight of 17) in those with a persistently occluded artery (P less than 0.001). In patients with inferior myocardial infarction, 2.4% (two of 82) with reperfusion and 22.2% (four of 18) with a persistently occluded artery died (P less than 0.01). CONCLUSIONS: Although the number of patients in the randomized groups was small, the trend toward a lower mortality after rescue PTCA supports the hypothesis that rescue PTCA may be beneficial. The mortality results in relation to presence or absence of reperfusion from the entire study population underscores the importance of achieving patency during myocardial infarction.

Aged↗
PubMed1991

Binding of IgG containing immune complexes to human neutrophil Fc gamma RII and Fc gamma RIII induces actin polymerization by a pertussis toxin-insensitive transduction pathway.

The ability of a phagocytic stimulus, rabbit IgG anti-BSA/BSA immune complexes, to increase the F-actin content of human polymorphonuclear leukocytes was quantitated by flow cytometry following staining with nitrobenzoxadiazole-phallacidin. A significant rise in F-actin assembly was induced by addition of 5 micrograms/ml immune complex. Concentrations of immune complex of more than 200 micrograms/ml caused a maximal (approximately twofold) increase in F-actin content. After a delay of 5 s, the F-actin levels rose and reached maximum levels by 60 s after adding immune complexes. The twofold elevation in F-actin persisted for up to 60 min. Both anti-Fc gamma RII and anti-Fc gamma RIII mAb blocked immune complex stimulated actin polymerization. Exposure to pertussis toxin failed to affect the rate or extent of immune complex-induced actin polymerization. Cells incubated with immune complexes and then lysed with Triton had an increased number of sites able to nucleate actin polymerization. These findings suggest that immune complex binding to both polymorphonuclear leukocytes Fc gamma RII and Fc gamma RIII is required for actin filament assembly and that the induction of assembly occurs via transduction pathways that differ from those used by chemoattractants. As with adhesion this phagocytic stimulus induces actin assembly by a pertussis toxin insensitive pathway and produces a rise in actin filament content that persists for prolonged periods of time.

Actins↗
PubMed1991

The effect of nitroglycerin on pulmonary vascular capacitance in dogs.

In this study we investigated the hypothesis that the decrease in pulmonary vascular pressures observed after administration of nitroglycerin is in part due to a shift in the pulmonary vascular pressure-volume relationship. The experiments were done in six closed-chest dogs anesthetized with pentobarbital, in which pulmonary, cardiac, and intestinal relative blood volumes were determined by equilibrium blood pool scintigraphy. Nitroglycerin (30 micrograms/kg/min) caused 7% (p less than 0.02) and 12% (p less than 0.02) reductions in pulmonary and total cardiac blood volume, respectively, and a 7% (p less than 0.01) increase in intestinal blood volume. This shift of blood from the heart and the pulmonary circulation to the systemic (intestinal) circulation was accompanied by reductions in mean pulmonary artery pressure from 16 +/- 2 mm Hg to 12 +/- 1 mm Hg (p less than 0.01), in mean pulmonary capillary wedge pressure from 11 +/- 2 mm Hg to 6 +/- 1 mm Hg (p less than 0.01), and in mean portal pressure from 9 +/- 1 mm Hg to 8 +/- 1 mm Hg (p less than 0.01). The position of the pulmonary vascular pressure-blood volume relationship was unaffected by nitroglycerin, whereas the portal pressure-intestinal blood volume relationship was shifted to the left and upward. These changes suggest that pulmonary vascular tone remained unchanged, whereas intestinal vascular tone decreased during administration of nitroglycerin. In conclusion, nitroglycerin decreased pulmonary vascular pressures through a passive emptying of the pulmonary circulation as a result of increased systemic (intestinal) vascular capacitance.

Animals↗
PubMed1991

Prediction of left ventricular mass from the electrocardiogram.

Multiple stepwise regression methods were used to derive electrocardiographic (ECG) models for prediction of the echocardiographic left ventricular (LV) mass index from standard 12-lead ECG measurements using data files of 203 men and 252 women. The correlation between echocardiographic and ECG estimates of LV mass index was R2 = 0.58 for men and R2 = 0.42 for women. A separate logistic regression model was derived for classification of LV hypertrophy as a dichotomized dependent variable. This classifier chose R (aVL), T (V6), and S (V1) for men and R (aVL), T (V6), and S (I) for women and produced a moderate sensitivity (53.7% for men and 63.4% for women) and specificity (94.9% for men and 92.9% for women). We conclude that the initial performance of these and other recently developed multivariate estimators of LV mass and LV hypertrophy classifiers is promising enough to subject them to further studies to evaluate their utility as risk predictors.

Adolescent↗
PubMed1991

Left and right ventricular diastolic function during acute pericardial tamponade.

The aim of the study was to determine the effect of acute pericardial tamponade on left (LV) and right ventricular (RV) intracavitary and transmural pressure-volume (P-V) relations and to assess the effect of changing blood volume during tamponade on LV and RV volumes. The experiments were done in 11 acutely instrumented anaesthetized dogs in which LV and RV volumes were determined by computed tomography (CT) (n = 5) and LV and RV diameters by sonomicrometry (n = 6). Pressures were measured in the pericardium (balloon transducer), in the aorta and in the ventricles. Incremental pericardial infusion (up to 180 ml) caused a progressive left and upward shift of the LV and the RV intracavitary P-V relationship. This shift was entirely due to increased pericardial pressure (PP). The induction of tamponade caused no change in the LV and RV transmural P-V relationship. During tamponade with ventricular filling pressures above 10-15 mmHg, blood volume expansion caused only minimal increase in LV and RV volumes. In conclusion, pericardial tamponade shifted the LV and the RV intracavitary diastolic P-V relation by increasing PP. However, there was no change in the transmural P-V relationship, indicating unchanged myocardial compliance. Volume loading caused only minimal increase in LV and RV volumes during tamponade.

Animals↗
PubMed1991

Differences in distensibility between the anterior and posterior walls of the left ventricle in dogs.

Nonuniformity of myocardial systolic and diastolic performance in the normal left ventricle has been recognized by a number of investigators. Lack of homogeneity in diastolic properties might be caused by or related to differences in the distensibility of different regions of the left ventricular (LV) wall. Thus, we compared the end-diastolic transmural pressure-strain relations in both the anterior and posterior LV walls in seven anesthetized dogs during two interventions (pulmonary artery constriction and aortic constriction). Transmural pressure was defined as the difference between LV intracavitary pressure and local pericardial pressure. LV pressure was measured using a micromanometer; pericardial pressures over the LV anterior and posterior walls were measured with balloon transducers. Circumferentially oriented pairs of sonomicrometer crystals were implanted in the midwall of the anterior and posterior walls of the LV to measure segment lengths. Strains were calculated as (L-L0)/L0, where L was the instantaneous segment length and L0 was the segment length when transmural pressure was zero. The pattern of end-diastolic transmural pressure--strain relations was similar in all dogs. The change in strain in the posterior wall was always greater than that in the anterior wall. Opening the pericardium did not affect the difference in distensibility of the anterior and posterior walls. The results suggest that the posterior wall is more compliant than the anterior wall (that is, for a given difference in transmural pressure, the local segment length change of the posterior wall was greater). This seems consistent with other observations, which suggest that the posterior wall might make a greater contribution to diastolic filling.

Animals↗