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Biomedical subjects

E R Smith

Publications and source records attributed to E R Smith.

At least 181 records · Page 10Linked to original sources

Androstenedione may organize or activate sex-reversed traits in female spotted hyenas.

Spotted hyenas (Crocuta crocuta Erxleben) present a unique syndrome of reversal in behavioral and anatomical distinction between the sexes: females are heavier and more aggressive than males and dominant over them. The female's external genitalia include a false scrotum and a fully erectile pseudopenis through which mating and birth take place. Results of studies of circulating testosterone levels in wild spotted hyenas do not account for the "male-like" characteristics of the female. Androstenedione, however, is consistently higher in females than in males, particularly during early infancy. Experiments on rodents show that androstenedione can be a potent organizer of anatomical and behavioral differentiation. This study suggests that it may also produce the profound virilization of female spotted hyenas.

Aging↗

Nonuniformity of pericardial surface pressure in dogs.

Previously, we have shown that pericardial constraint cannot be measured by true (hydrostatic) pressure except when an excess of pericardial fluid is present and that a device such as a balloon (which reflects radial contact stress as well as hydrostatic pressure) must be used. Since radial contact stress is the major component of the constraint exerted by the pericardium when little pericardial liquid is present, it follows that the pressure measured by the balloon might be different over different parts of the heart. In an attempt to test this hypothesis, in 11 anesthetized dogs we placed pericardial balloons over the right and left ventricular free walls, instrumented the animals to measure ventricular dimensions (sonomicrometry) and pressure, mounted pneumatic constrictors on the aortic and pulmonary artery, reapproximated the pericardium, and closed the chest under suction. We studied the transient effects of constrictions of the ascending aorta and pulmonary artery and of angiotensin infusion before and after intravenous saline infusion. Aortic constriction and, to a lesser degree, angiotensin increased pericardial pressure over the left ventricle more than over the right ventricle. Pulmonary artery occlusion increased pericardial pressure over the right ventricle but significantly decreased pericardial pressure over the left ventricle. We conclude that there are significant local differences in pericardial pressure (recorded by balloon) over the lateral ventricular surfaces during acute changes in afterload. These observations may be explained in part by decreased venous return to the contralateral ventricle, the tendency of the heart to resist lateral displacement, and the limited mobility of the pericardium.

Animals↗

Modulation of vascular capacitance by angiotensin and nitroprusside: a mechanism of changes in pericardial pressure.

The aim of the present study was to test the hypothesis that vasoactive drugs may modify left ventricular diastolic function by shifting blood between the systemic vascular bed and the heart, thereby changing pericardial and left ventricular pressure. The experiments were done in 10 open-chest, anesthetized, previously splenectomized dogs in which changes in pericardial surface pressure in response to intravenous sodium nitroprusside and angiotensin were related to changes in blood volume in the abdominal region. Blood volume was determined by blood pool scintigraphy (99mTc) and regions of interest were drawn in the liver and in the mesenteric area. Angiotensin was infused at rates that were adjusted to increase mean aortic pressure by 20 and 30 mm Hg, and nitroprusside was infused at rates to decrease mean aortic pressure by 30 and 50 mm Hg. Angiotensin increased pericardial pressure by 3 and 5 mm Hg at the respective doses and there were increments in left ventricular end-diastolic pressure (LVEDP) and left ventricular diameter (sonomicrometry). Angiotensin decreased blood volume in the mesenteric region by 14% and 17%, but did not significantly change blood volume in the liver region. Angiotensin increased portal venous pressure and decreased mesenteric blood volume, suggesting decreased mesenteric venous compliance. Nitroprusside had opposite effects: pericardial pressure was decreased by 5.5 and 6.5 mm Hg by the respective doses. The doses of nitroprusside increased blood volume in the mesenteric region by 14% and 20%, but did not significantly change blood volume in the liver region.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Transseptal pressure gradient and diastolic ventricular septal motion in patients with mitral stenosis.

Previous studies from our laboratory have shown that the position of the ventricular septum relative to the two ventricles at end-diastole is determined by the instantaneous transseptal pressure gradient (TSG) defined as left ventricular minus simultaneous right ventricular pressure. Since patients with mitral stenosis often have exaggerated leftward (paradoxic) motion of the ventricular septum during early diastole, we studied seven patients with mitral stenosis undergoing cardiac catheterization to determine if position (and therefore motion) of the ventricular septum was determined by TSG throughout diastole. M Mode echocardiograms derived from a two-dimensional parasternal short-axis view were recorded with simultaneous micromanometer measurements of left ventricular and right ventricular pressures. Six of seven patients demonstrated abnormal early diastolic leftward motion of the ventricular septum in at least one cardiac cycle. TSG measured at intervals throughout diastole ranged from -2.5 to +20 mm Hg, with abnormal TSG observed in most of the 40 cardiac cycles selected for analysis. The intracardiac position of the ventricular septum, defined as the distance from the right ventricular epicardium (RVEpi) to the left surface of the ventricular septum normalized for total cardiac dimension (RVEpi-VS), was plotted against left ventricular pressure, right ventricular pressure, and TSG. Linear regression of pooled data from all patients (164 observations) demonstrated a highly significant correlation between the instantaneous TSG and the relative intracardiac position of the ventricular septum (RVEpi-VS = 1.52 TSG + 42.7; r = .79, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparison of retrobulbar block produced by etidocaine 1% and by a mixture of lidocaine 2% and bupivacaine 0.75%.

In this double-blind study, retrobulbar block for cataract surgery was produced in 43 patients with etidocaine 1% and in 37 patients with a mixture of equal volume of lidocaine 2% and bupivacaine 0.75% (final concentrations of 1% and 0.375%, respectively). While a greater proportion of etidocaine-treated patients needed supplemental drug for block, the times of onset of sensory and motor block were not different for the two groups. Compared to treatment with etidocaine, patients treated with the mixture had a slower recovery of motor function. While the proportion of patients reporting postoperative pain was about the same in each group, both the onset of pain and the use of analgesic agents occurred earlier in the group treated with etidocaine. Thus retrobulbar blocks produced by the combination of lidocaine and bupivacaine occurred as rapidly as those produced by etidocaine but had a longer duration.

Acetanilides↗

Usefulness of noninvasive studies for diagnosis of right ventricular dysplasia.

The value and limitations of echocardiography and cardiac scintigraphy in the diagnosis of right ventricular (RV) dysplasia were assessed. Criteria that defined RV dysfunction were developed first using data from 40 normal subjects. The sensitivity and specificity of these criteria to detect RV dysplasia were then determined in 44 patients suspected of having RV dysplasia. In these patients the presence (14 patients) or absence (30 patients) of RV dysplasia had been established using cardiac catheterization data, which included contrast RV cineangiograms. Mean RV end-diastolic and end-systolic diameters, and RV/left ventricular (LV) ratios of end-diastolic and end-systolic diameters and end-diastolic and end-systolic volumes were greater in patients with RV dysplasia (p less than 0.001). Using cardiac scintigraphy, all patients with RV dysplasia were identified by an RV/LV end-systolic volume greater than 1.8; exercise RV ejection fraction less than 50%; or exercise RV wall motion score more than 1. Using echocardiography, RV contraction abnormalities were seen in 80% of patients with RV dysplasia. The specificities, even in this selected population, were less than 100%. Thus, normal echocardiographic and scintigraphic results can be used instead of RV contrast cineangiography to exclude the diagnosis of RV dysplasia.

Adult↗

A mechanism for the nitroglycerin-induced downward shift of the left ventricular diastolic pressure-diameter relation.

Nitroglycerin has been shown to cause a downward shift in the left ventricular (LV) pressure-volume relation in patients. To test the hypothesis that this shift is mediated by an alteration in pericardial pressure, 13 patients undergoing diagnostic cardiac catheterization were studied. LV and right ventricular (RV) pressure (micromanometers) and LV diameter (2-dimensional echocardiography) were measured simultaneously before and after sublingual administration of 0.3 to 0.6 mg of nitroglycerin. In the 11 patients with hemodynamic effects from nitroglycerin, mean LV end-diastolic pressure decreased from 12.7 +/- 5 mm Hg (mean +/- standard deviation) to 7.3 +/- 3 mm Hg (p less than 0.002) and mean RV end-diastolic pressure declined from 7.7 +/- 3 mm Hg to 5.0 +/- 1 mm Hg (p less than 0.001). However, nitroglycerin caused only a slight (6%) reduction in LV minor axis diameter, from 52 +/- 8 mm to 49 +/- 9 mm (p less than 0.05). Diastolic pressure-diameter plots constructed from early and late diastolic measurements demonstrated a downward shift in the relation. However, when RV end-diastolic pressure was used as an estimate of pericardial pressure (a procedure validated by studies in our laboratory), the transmural pressure-diameter points before and after administration of nitroglycerin defined a single curve. These observations are in keeping with the conclusions that nitroglycerin did not alter the elastic properties of the myocardium and that the decrease in LV end-diastolic pressure induced by nitroglycerin was primarily attributable to a reduction in external constraint.

Adult↗

Failure of pimozide and metergoline to antagonize the RDS-127-induced facilitation of ejaculatory behavior.

Metergoline, a serotonin-receptor antagonist, when administered in either an ascorbic acid or ethanol containing vehicle was without effect on male rat copulatory behavior (3 mg/kg, 90 minutes pretest). When initially dissolved in several drops of acetic acid, however, the same dose of metergoline dramatically suppressed male rat sexual behavior. Thus, one-half of the treated rats failed to intromit and ejaculate, and those displaying the behaviors exhibited elongated intercopulatory and postejaculatory intervals. The administration of the putative dopamine-receptor agonist RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane; 3 mg/kg, six minutes pretest) induced seminal emission ex copula and drastically reduced intromission frequency and ejaculation latency in copula, as well as effecting lesser reductions in the intercopulatory and postejaculatory intervals in two sequential copulatory series. RDS-127-induced seminal emission was effectively antagonized by pretreatment with the dopamine-receptor antagonist pimozide (250 micrograms/kg, two hours pretest), but not by pretreatment with metergoline. In contrast to seminal emission ex copula, pimozide pretreatment failed to antagonize the RDS-127 facilitation of ejaculatory behavior in copula. Metergoline pretreatment also failed to antagonize the RDS-127-induced facilitation of ejaculatory behavior in copula. However, RDS-127 prevented the suppressive effects of metergoline treatment, suggesting that RDS-127 has some agonistic action at serotonergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assessment of pericardial constraint: the relation between right ventricular filling pressure and pericardial pressure measured after pericardiocentesis.

Experimental studies have shown that right ventricular filling pressure (that is, intracavitary diastolic pressure) approximates pericardial surface pressure but, in many patients after removal of pericardial effusion, right ventricular filling pressure has been found to markedly exceed pericardial pressure recorded by an open catheter. The aim of this study was to determine whether this apparent contradiction was related to the technique of pericardial pressure measurement. Nine patients with chronic pericardial effusion were studied and, although these pressures diverged to varying degrees in individual patients, the previous observation was confirmed in that, although initially similar, right ventricular filling pressure and pericardial pressure (measured by means of an open catheter) tended to diverge during removal of the effusate; when the evacuation was as complete as possible pericardial pressure was 2.1 +/- 1.0 (mean +/- SE), while right ventricular filling pressure was 8.7 +/- 1.7 mm Hg (p less than 0.01). In six open chest, anesthetized, volume-loaded dogs with pericardial effusion (50 ml), right ventricular filling pressure and pericardial pressures measured with both open catheter and flat balloon were all equal. With decreasing volume of pericardial fluid, right ventricular filling pressure and pericardial pressure (by catheter) diverged as had been observed in patients. However, pericardial pressure (balloon) continued to be equal to right ventricular filling pressure. (With 0 ml in the pericardium, right ventricular filling pressure = 12.9 +/- 0.9 mm Hg, pericardial pressure [catheter] = 1.4 +/- 1.9 mm Hg and pericardial pressure [balloon] = 12.4 +/- 1.5 mm Hg.) Thus, these observations support the use of right ventricular filling pressure as an estimate of pericardial constraint in patients.

Adult↗

Differential interactions of "prosexual" drugs with 5-hydroxytryptamine1A and alpha 2-adrenergic receptors.

Radioligand binding studies were used to analyze the interactions of six "prosexual" drugs with 5-hydroxytryptamine1A (5-HT1A) and alpha 2-adrenergic receptors in rat brain membranes. Three drugs that facilitate seminal emissions and/or ejaculations [8-hydroxy-2-n-propylaminotetralin (8-OH-DPAT), 5-methoxy-dimethyltryptamine, and RDS-127] are potent and selective inhibitors of [3H]8-OH-DPAT binding to 5-HT1A receptors. By contrast, three drugs with primary sexual arousal effects (yohimbine, imiloxan, and idazoxan), are potent agents at alpha 2-adrenergic receptors labeled by [3H]yohimbine. These data suggest that radioligand binding analysis of prosexual agents may elucidate the pathophysiology of sexual behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Creep of the canine pericardium in vivo.

In eight open chest dogs we assessed the creep of the pericardium by measuring the increase in surface area of the pericardium, occurring after pericardial surface pressure (Ppe) was rapidly increased by inflating an air-containing balloon positioned between the pericardium and the left ventricular (LV) epicardium. We observed an increase in LV end diastolic pressure (EDP) of 3.6 +/- 3.4 mmHg (1 mmHg = 133.3 Pa) (p less than 0.05) (mean +/- SD) and a reduction in LV anteroposterior (AP) diameter of 8.8 +/- 6.1 mm (p less than 0.01), both of which were stable after 10 s. Mean Ppe increased 11.6 +/- 3.3 mmHg (p less than 0.001). Pericardial surface lengths at 45 and 135 degrees to the long axis of the LV were measured with two pairs of ultrasonic crystals attached to the outer surface of the pericardium. The beam of ultrasound travelling between each pair was directed parallel to the pericardial surface through a film of conducting medium. Initial increase in surface area (calculated as the product of two pericardial lengths) occurring during the first 15 s after balloon inflation was 5.8 +/- 2.5% (p less than 0.001). During the next 30 min, while mean pericardial pressure did not change, pericardial surface area increased another 2.8% (p less than 0.005). This time-dependent 2.8% increase in pericardial surface area (equivalent to an increase in volume of approximately 5%) is due to creep.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The relationship between pericardial pressure and right atrial pressure: an intraoperative study.

The objective of this study was to determine the constraining effect of the normal human pericardium. Accordingly, immediately after thoracotomy in nine patients undergoing elective cardiac surgery, we measured mean pericardial surface pressure over the lateral free wall of the left ventricle with a flat balloon as well as mean right atrial pressure while incrementally infusing up to 2.1 liters of Ringer's solution to increase right atrial pressure. In each case, the slope of the relationship between right atrial (range -4 to 20 mm Hg, overall) and pericardial pressures was near unity (1.16 +/- 0.20 mean +/- SD) and the intercept was approximately zero (0.71 +/- 2.48 mm Hg). Correlation coefficients ranged from .86 to .97. These observations suggest that right atrial pressure can be used as an estimate of pericardial surface pressure. If this is the case, true left ventricular preload (i.e., effective distending pressure or transmural diastolic pressure) might be estimated from the difference between left ventricular filling pressure and right atrial pressure, both conveniently measurable clinically by means of a triple-lumen, flow-directed catheter.

Aged↗

Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potential.

It is now well established that the vulnerability of the ventricular myocardium to repetitive dysrhythm increases in the presence of greater than normal disparity local recovery times. Local recovery is reflected in the electrocardiographic waveform as an area of the ventricular deflection (QRST time integral), and thus disparate ventricular recovery may be manifested in the body surface distribution of this quality. To assess this possibility, we obtained simultaneous 120-lead electrocardiograms from both the anterior and posterior torso in 140 subjects (ages 8 to 75) grouped as follows: group A, 97 normal subjects; group B, 16 patients resuscitated from ventricular fibrillation or sustained ventricular tachycardia; and group C, 27 patients 6 to 12 months after myocardial infarction but without clinically significant arrhythmia. In each subject, the QRST integral was evaluated for each lead and isointegral contour maps were plotted. A score was assigned to each map, based on the number of extrema; each maximum or minimum scored one point, with the exception of simultaneously occurring anterior and posterior minima on the right shoulder (frequently occurring in normal subjects), which scored together only one point. All but one group A subject had dipolar QRST integral maps (mean +/- SD score 2.11 +/- 0.2). Conversely, 10 of 16 (62.5%) group B patients had scores of 3 or more (mean 3.16 +/- 1.08; p less than .01 vs group A). Group C patients had intermediate values, with eight of 27 (29.6%) scoring 3 or more (mean 2.46 +/- 83); this was less than in group B (p less than .01), but more (p less than .05) than in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects on canine prostatic secretion of some drugs that modify ion transport.

The effects of acetazolamide, amiloride, furosemide, ouabain and theophylline on nerve-induced prostatic secretion were determined in pentobarbital-anesthetized dogs. In one set of experiments the glands were exposed to normal saline or drug-containing saline between periods of nerve-induced secretion by connecting a urethral cannula for 30-min periods to a buret filled with normal saline or drug-containing saline at a height of 100 cm above the gland and by allowing retrograde penetration of these solutions into the gland. Secretion in response to stimulation of the hypogastric nerves at 20 Hz was markedly inhibited by intraurethral exposure to 0.1 and 1 mM ouabain but not to 10 mM furosemide, 3 mM amiloride or 30 mM theophylline; responses to stimulation at 2 Hz were potentiated by 30 mM theophylline. In other experiments, secretion in response to stimulation at 20 Hz was inhibited by i.v. administration of 10 to 30 mg/kg of furosemide but not 2 to 8 mg/kg of amiloride or 18.5 to 25 mg/kg of acetazolamide. Because active Cl- transport is a major process in canine prostatic fluid formation and because secretion of this fluid was selectively modified by these drugs in the same manner as is Na+,K+-coupled active Cl- transport by a variety of other epithelia, these epithelia appear to share a common Cl- transporting system.

Acetazolamide↗

Nuclear cardiology techniques in the assessment of ischemic heart disease.

Invasive techniques of cardiac catheterization and angiography have become the gold standard for the diagnosis and management of patients with ischemic heart disease. More recently there has been a remarkable development of noninvasive imaging techniques which has resulted in improved ability to select patients in need of invasive investigations and in a more complete understanding of the physiological and clinical significance of information obtained from such invasive investigations. The value and limitations of the 3 most common techniques, radionuclide ventriculography, myocardial perfusion scintigraphy and acute myocardial infarction scintigraphy, are discussed in this review in relation to the assessment of patients with proven or suspected ischemic heart disease. These nuclear cardiology techniques are now available in most hospitals with nuclear medicine equipment; a good understanding of the strengths and weaknesses of each technique is essential for optimal clinical use.

Angiocardiography↗

Isosorbide dinitrate and glyceryl trinitrate: demonstration of cross tolerance in the capacitance vessels.

Cross tolerance to the arterial effects of sublingual glyceryl trinitrate (GTN) has been demonstrated in subjects taking oral isosorbide dinitrate (ISDN). To determine if cross tolerance also develops in the venous system, the effects of 0.6 mg of GTN on venous capacitance were assessed before (stage A) and during (stage B) therapy with ISDN. Venous capacitance was assessed using the radionuclide blood pool method, with relative changes in regional blood volume measured in the forearm in 6 patients and the splanchnic circulation in 4 patients. Heart rate, blood pressure and blood volume were measured before and at 1-minute intervals for 10 minutes after GTN; there was less than 2% variability in regional blood volume during 6 control measurements. During stage A, 5 minutes after GTN, systolic blood pressure (mean +/- standard deviation) decreased by 14% (from 125 +/- 15 to 107 +/- 19 mm Hg, p less than 0.01) and heart rate increased by 17% (from 68 +/- 14 to 80 +/- 17 beats/min, p less than 0.001), while regional blood volume increased to 101 +/- 2% at 1 minute (difference not significant [NS]), 111 +/- 2% at 5 minutes (p less than 0.001) and 107 +/- 3% at 10 minutes (p less than 0.01) relative to baseline measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Secretion of bromide by the canine prostate.

Four dogs with surgically produced prostatic fistulas were given single oral doses of 1.13 gm of sodium bromide daily for five consecutive days. Two days later the mean (+/- SE) serum level of bromide was 28.0 +/- 4.0 meq/L and the serum chloride level had decreased from a pretreatment value of 112.5 +/- 1.0 meq/L to 86.5 +/- 3.7 meq/L; in the basal prostatic secretion, the mean prostatic fluid to serum (PF/S) ratios for bromide and chloride were 0.56 +/- 0.15 and 0.53 +/- 0.11, respectively, and were not different (P greater than 0.05, paired t-test); at higher rates of secretion provoked by intravenous pilocarpine the corresponding PF/S ratios of 1.48 +/- 0.04 and 1.32 +/- 0.01 were significantly different (P less than 0.05, paired t-test). It is concluded that the processes involved in forming the basal and pilocarpine-induced prostatic secretions must differ and that the ability of the chloride-transporting system to transport bromide is slightly greater than that for chloride. Because it may impair sperm motility, bromide secreted in prostatic fluid potentially could adversely affect reproduction.

Animals↗

Testosterone is not required for the enhancement of sexual motivation by yohimbine.

Yohimbine HCL (2 mg/kg, 20 min prior to testing) administration was followed by significant decreases in the latencies to initial mount, intromission and ejaculation in castrated male rats bearing 2 mm testosterone-containing Silastic capsules 51 days after castration. Further, yohimbine stimulated copulatory activity in castrated, nonhormone-treated male rats up to 91 days after castration. Finally, yohimbine induced mounting in intact, nonreceptive female rats. These observations indicate that testosterone is not required for the enhancement of sexual motivation by yohimbine and support the suggestion that alpha 2-adrenoceptors are involved in the modulation of sexual arousal.

Animals↗