Comparison of left atrial volume by two-dimensional echocardiography and cine-computed tomography.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R M Weiss.
Explore the source record for details and available documents.
We investigated the binding characteristics of endothelin (ET) receptors in rabbit ureter, bladder dome, bladder base, and urethra and compared the observed receptor properties with those of cloned human ETA and ETB receptors expressed in Chinese hamster ovary K-1 (CHO) cells. Receptor binding experiments with [125I]ET-1 revealed the presence of a single class of specific, saturable, high affinity [125I]ET-1 binding sites in all of the regions of the studied urinary tract. The rank order of the densities (Bmax values) of [125I]ET-1 binding sites was: ureter "bladder dome > bladder base = urethra. ET-1 and ET-2 inhibited [125I]ET-1 binding to the membrane particulates from the various regions of the urinary tract with single high affinity constants. A selective ETA receptor antagonist, BQ 123, and selective ETB agonists, ET-3 and sarafotoxin S6c (STXc), inhibited [125I]ET-1 binding to bladder dome, bladder base, and urethra with high and low affinity constants indicating the presence of both ETA and ETB receptor subtypes in these tissues. The subtype specificity of ET receptors in the rabbit tissues is confirmed with inhibition data obtained from similar binding studies in cloned human ETA and ETB receptors. The proportions of high affinity binding sites for ET-3, representing ETB receptors, were approximately 25%, 27%, and 46% in bladder dome, bladder base, and urethra, respectively. Corresponding values for STXc were approximately 17%, 28%, and 43% in bladder dome, bladder base, and urethra, respectively. In contrast to the findings for ET-3 and STXc, the proportions of high affinity binding sites for BQ 123, representing ETA receptors, in bladder dome, bladder base, and urethra were approximately 84%, 74%, and 60%, respectively. In ureter, these selective compounds inhibited [125I]ET-1 binding with either a low (ET-3 and STXc) or a high binding affinity (BQ 123), suggesting the presence of only a single receptor subtype (ETA) in this tissue. These data indicate that there are regional differences in the density and subtype specificity of ET receptors in the rabbit urinary tract.
The relaxant effects of norepinephrine (NE, 10(-7) to 10(-4) M.) and isoproterenol (ISO, 10(-9) to 10(-4) M.) on maximal KCl-induced tonic contractions and the relaxant effects of ISO on contractions induced by electrical field stimulation (EFS) were measured in detrusor muscle strips obtained from 22-25 day, 90-95 day and 22-month-old male Fischer 344 rats. The maximum relaxant response to NE and ISO on KCl-induced tonic contractions decreased significantly with increasing age. The ED50 values for ISO, but not NE, increased with age. The maximum relaxant response to ISO on EFS-induced contractions also was reduced significantly in the old bladders. The relaxation effects of forskolin (10(-6) to 3 x 10(-5) M.), dibutyryl cyclic AMP (DBcAMP, 10(-4) to 3 x 10(-3) M.) and cholera toxin (10 micrograms/ml.) were examined on maximal KCl-induced contractions of the muscle strips obtained from the three age groups. The relaxant responses to forskolin decreased significantly with increasing age, whereas DBcAMP relaxed the muscle strips from the three age groups equally. Cholera toxin (10 micrograms) attenuated KCl-induced phasic contractions, and this effect was impaired in the aged rat detrusor. The density of beta-adrenergic receptors, as determined by radioligand binding with [125I]iodopindolol ([125I]-PIN) decreased with increasing age. These data demonstrate an age-related decrease in the responsiveness of the bladder detrusor to beta-adrenergic stimulation that may be related to the decreased density of beta-adrenergic receptors and decreased cyclic AMP (cAMP) production.
Muscarinic cholinergic and adrenergic agonist-induced changes in [3H]-phosphatidyl inositol (PI) hydrolysis and cyclic AMP (cAMP) levels were measured in guinea pig ureter, urethra and bladder dome. In the ureter, carbachol, norepinephrine and phenylephrine rapidly increased PI hydrolysis and basal cAMP levels, but did not decrease forskolin-stimulated cAMP levels. In the bladder dome, norepinephrine and phenylephrine produced a rapid but transitory increase in PI hydrolysis, but did not affect forskolin-stimulated cAMP levels. Carbachol produced a rapid and sustained increase in PI hydrolysis and also, at high concentrations, decreased forskolin-stimulated cAMP levels. In the urethra, norepinephrine and carbachol rapidly decreased forskolin-stimulated cAMP levels and later increased PI hydrolysis. Our data suggest that the predominant second messenger system in the ureter, dome, or urethra is more dependent on the tissue than on the agonist. These tissue-specific, agonist-induced rapid changes in second messenger levels may help coordinate the contraction-relaxation phenomena necessary for urinary tract function.
Soluble and particulate fractions from rabbit urethra converted [14C]arginine to [14C]citrulline, indicating the presence of nitric oxide synthase activity in these fractions. Both soluble and particulate nitric oxide synthase activities were NADPH dependent, and the soluble activity was Ca2+ dependent. Three nitric oxide synthase (NOS) inhibitors affected transmural nerve stimulation induced relaxation responses in the rabbit urethra and the activity of soluble nitric oxide synthase with the same rank order of potency, i.e., NG-nitro-L-arginine (NNA) > NG-methyl-L-arginine (NMA) > canavanine (CAN). The rank order of potency with respect to particulate NOS activity was CAN > NMA = NNA. The relaxation responses to electrical stimulation were accompanied by increases in cyclic GMP. These results suggest that NOS activity found in the soluble fraction of urethral homogenates produces nitric oxide that in turn increases cyclic GMP levels which mediates the relaxation responses induced by transmural nerve stimulation in the rabbit urethra.
We used cine computed tomography (CT) to determine whether decreased mitral valve gradients and pulmonary artery pressures resulted in decreased right ventricular and atrial volumes after percutaneous mitral balloon commissurotomy (MBC). In patients treated for severe mitral stenosis, previous studies have shown that after the mitral valve gradient decreases, the left atrial volume is reduced and left ventricular stroke volume is increased. The effects of commissurotomy on right heart chamber sizes have been difficult to assess with angiography and echocardiography. Moreover, in follow-up studies performed after surgery, changes in cardiac chamber volumes occurring after the mitral valve gradient and pulmonary pressure are reduced are confounded by the effects of thoracotomy. Our group has previously demonstrated that cine CT can accurately measure both left and right cardiac chamber volumes. We studied 11 female patients before, immediately after, and at 1 year after MBC, and 9 female control subjects of comparable age. To assess cardiac chamber volumes, we used cine CT. To assess the effects of MBC, we used cardiac catheterization and Doppler echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: The purpose of this study was to develop and test a method for quantitation of regional myocardial perfusion using cine computed tomography. BACKGROUND: Cine computed tomography is a relatively new cardiac imaging technique with excellent temporal and spatial resolution. Application of this technique to the study of human coronary circulation could substantially broaden our knowledge of human cardiac pathophysiology. This goal has been previously approached with some success. However, no method to date has shown validated accuracy of regional perfusion measurements over the entire range of physiologically important flow states. METHODS: Eight anesthetized dogs underwent thoracotomy for instrumentation. They were then studied during baseline flow conditions, after coronary vasodilation with intravenous dipyridamole and after coronary stenosis or occlusion. Regional myocardial perfusion was assessed by cine computed tomography using a method that includes estimates for myocardial blood volume and rate of myocardial enhancement after an aortic root contrast medium infusion. Measurements made nearly simultaneously by the radioactive microsphere method served as a reference standard. RESULTS: A total of 32 perfusion conditions were studied with a range of 4 to 593 ml/min per 100 g. There was reasonable agreement between the two methods of measurement throughout the whole range of perfusion states: r = 0.97, regression slope 0.99, intercept 2 ml/min per 100 g. In zones not subserved by a stenosed or occluded artery, cine computed tomography accurately depicted perfusion homogeneity with a coefficient of variation of 13 +/- 1% (mean +/- SE) versus 11 +/- 1% for the microsphere method (p = NS). CONCLUSIONS: Cine computed tomography is capable of providing accurate, quantitative assessment of regional myocardial perfusion over a broad range of perfusion states. This method, if extended to the study of humans, could enhance the understanding of disorders of the coronary circulation in human cardiovascular disease states.
Muscarinic cholinergic receptors were identified and characterized by radioligand receptor binding assay using [3H]quinuclidinyl benzilate (QNB) in rat vas deferens membrane particulates of three experimental groups: 1) 8-week diabetic, 2) 8-week diabetic insulin-treated and 3) age-matched control. Diabetes was induced by the intravenous injection of 65 mg./kg. streptozotocin (STZ). The density of muscarinic receptors (Bmax values), as determined by saturation experiments with [3H]QNB, was demonstrated to be higher in the vas deferens of diabetic rats than in the vas deferens of control and diabetic insulin-treated rats. The equilibrium dissociation constants (KD values), however, were similar in all three groups. Muscarinic cholinergic antagonists competed with [3H]QNB binding sites in the vas deferens membrane particulates with the following rank order of Ki values: atropine < methoctramine < or = 4-DAMP < AF-DX 116 < HHSiD < pirenzepine = pfHHSiD. The pharmacological profile of muscarinic receptors was similar in all three groups. Additional pharmacological studies showed a similar rank order of Ki values for vas deferens, bladder dome and heart, but this rank order was significantly different in cerebral cortex and prostate. This is consistent with the predominance of the M2 muscarinic cholinergic receptor subtype in the rat vas deferens. It is concluded that STZ-induced diabetes causes an upregulation of muscarinic cholinergic receptor density in the rat vas deferens that can be prevented by the administration of insulin.
To further define the endogenous sources of urine nitrite in urinary tract infections, we measured urinary nitrite levels by the Griess method and assayed urinary nitric oxide (NO) synthase activity by the conversion of 14C-arginine to 14C-citrulline. Endogenous production of 14C-citrulline was confirmed by thin layer chromatography. Exogenous L-arginine increased nitrite production in whole infected urine, but not in bacteria isolated from infected urine. Urinary tract infections significantly increased NO synthase activity in soluble urine fractions, although soluble activity was less than 10% of particulate activity. Urine particulate fractions from women with non-infected urine had greater NO synthase activity than particulate fractions from men with non-infected urine, 11 +/- 2 and 0.2 +/- 0.1 picomol/min/mg protein, respectively. Urinary tract infections increased NO synthase activity in urine particulate fractions from women and men, 99 +/- 20 and 48 +/- 9 picomol/min/mg protein, respectively. The conversion of 14C-arginine to 14C-citrulline required NADPH, was calcium independent, and was inhibited to a greater extent by L-canavanine than by NG-monomethyl-L-arginine or NG-nitro-L-arginine. Human infected urine contains an isoform of NO synthase which is an endogenous source of urine nitrite.
RATIONALE AND OBJECTIVES: Determination of coronary artery patency may have therapeutic and prognostic significance particularly in the setting of acute myocardial infarction. Previous studies with cine computed tomography have demonstrated remarkable accuracy in the determination of coronary artery bypass graft patency. Recent improvements in resolution capability have afforded the potential for determination of native coronary artery patency. The accuracy of coronary artery patency determined by cine computed tomography is investigated in an animal model of coronary occlusion-reperfusion. METHODS: Seven anesthetized dogs were studied during control, coronary occlusion, and reperfusion conditions. Cine computed tomography was performed using electrocardiogram-triggered serial scans after intravenous injection of contrast medium. Coronary patency was determined by dye appearance in the epicardial artery coincident with its appearance in the left ventricular cavity. RESULTS: Patency was determined for the left anterior descending and left coronary arteries during three separate conditions in each dog, for a total of 42 patency determinations, and yielded the correct result in all cases. CONCLUSION: High-resolution cine computed tomography scanning can provide accurate determinations of coronary artery patency in an experimental model of occlusion-reperfusion.
RATIONALE AND OBJECTIVES: Mitral balloon commissurotomy (MBC) can successfully increase the mitral valve area (MVA) in mitral stenosis, but the outcome is variable. In multicenter studies, qualitative echocardiographic scores obtained before MBC are only weakly predictive of the increase in MVA after MBC. METHODS: To evaluate whether the change in MVA after MBC can be predicted by evaluating mitral valve morphology using cine computed tomography (CT), we studied 12 women with mitral stenosis and 11 female control subjects. RESULTS: In the patients with mitral stenosis, MVA increased from 1.13 +/- 0.24 to 1.93 +/- 0.56 cm2 (P < .0001) after MBC. A standard echocardiographic score assessment of mitral valve morphology before MBC was not associated with the change in MVA after MBC in these patients (P > .20). However, the total mitral valve morphology score evaluated by cine computed tomography was strongly associated with the change in MVA after MBC (r = -.87; P < .0005). In addition, the individual morphologic characteristics of mitral valve mobility (P < .0025), leaflet thickness (P < .05), and subvalvular disease (P < .05) were significant predictors of the change in MVA after MBC. CONCLUSION: Cine computed tomography may be useful for predicting immediate increases in MVA in patients after MBC and may be helpful for preoperative assessment of these patients.
Different free T4 (FT4) assays often give different FT4 measurements, and conflicting measurements have been striking in nonthyroidal illness. Because FT4 immunoassays depend upon serum protein-bound T4 (PBT4) dissociation to stabilize the FT4 concentration during assay perturbations, interassay differences in perturbations combined with variation in serum PBT4 concentrations could produce discordant FT4 measurements. This study examined the effects of PBT4 on FT4 measurements obtained by direct immunoassay methods. Standard solutions with constant FT4 levels and varying PBT4 concentrations were prepared and analyzed by direct equilibrium dialysis, two-step immunoextraction, one-step labeled T4 antibody, and one-step labeled T4 analog FT4 methods. Direct equilibrium dialysis results were independent of PBT4 concentrations and gave correct measurements of serum FT4 when the PBT4 concentration was above 8 nmol/L or 0.6 micrograms/dL, but were PBT4 dependent and underestimated serum FT4 at lower PBT4 concentrations. The other three methods were PBT4 dependent and variably underestimated serum FT4 at all levels of PBT4 up to 256 nmol/L (19.9 micrograms/dL), the highest level studied. Thus, PBT4-dependent underestimates of serum FT4 occurred with all four methods, whereas the measured FT4 level at each PBT4 concentration varied widely between methods. A serum PBT4 dependent bias causes discordant FT4 measurements and probably explains the observed underestimates of FT4 in nonthyroidal illness.
Previous studies from our laboratory demonstrated that 8 weeks of streptozocin (STZ)-induced diabetes and sucrose-fed diuresis resulted in increases in the density of muscarinic receptors in rat bladder dome and that early insulin treatment (started 3 days after the onset of diabetes) prevented the diabetes-induced upregulation (J Pharmacol Exp Ther 248:81-88, 1989; Diabetes 40: 1150-1156, 1991; J Urol 147:760-763, 1992). To determine whether diabetes- and diuresis-induced alterations in muscarinic receptors in rat bladder dome are reversible, we administered insulin (beginning 8 weeks after the onset of diabetes) or removed sucrose from drinking water of diuretic rats (beginning 8 weeks after the onset of diuresis). Five groups of rats were maintained for 16 weeks: 1) STZ-induced diabetic rats (65 mg/kg intravenously); 2) insulin-treated diabetic rats (5-8 U/day insulin subcutaneously beginning 8 weeks after the onset of diabetes); 3) sucrose-fed diuretic rats (5% sucrose in drinking water throughout 16 weeks); 4) sucrose-removed rats (sucrose withdrawn from drinking water after 8 weeks of the sucrose-induced diuretic state); and 5) age-matched control rats. Radioligand receptor binding experiments with [3H]quinuclidinyl benzilate showed an increase in the density of muscarinic receptors in bladder dome of diabetic and sucrose-fed rats compared with age-matched control rats. Removing the 5% sucrose from the drinking water of diuretic rats reversed the increased water intake and urine output, decreased the bladder hypertrophy that accompanied the diuretic state, and corrected the upregulation of the muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
(+)-[3H]PN 200-110 and [3H]nitrendipine binding sites were studied in 1 day, 6 week, 6 month and 4.5-5 year rabbit urethra, bladder base and bladder dome. In all age groups, the density of these Ca2+ channel antagonist binding sites was significantly greater in the urethra than in the bladder base or bladder dome, except that the density of [3H]nitrendipine binding sites in the 1 day rabbit was similar in all three regions. In the urethra the maximum number of binding sites for (+)-[3H]PN 200-110 was twice that for [3H]nitrendipine. In the bladder base and bladder dome both Ca2+ channel antagonists labelled a similar number of binding sites. For both ligands, the Bmax values for the Ca2+ channel antagonists in the urethra increased from 1 day to 6 weeks and then decreased. In the bladder base and dome, however, the receptor density decreased gradually or was unchanged with aging. The pharmacological profiles of these binding sites in 1 day and 6 month urethra and bladder dome showed K1 values with the following rank order: nitrendipine < niguldipine < BAY K 8644. These data demonstrate the presence of regional- and age-dependent changes in the density of Ca2+ channel antagonist binding sites in the lower urinary tract of the rabbit.
OBJECTIVES: The purpose of this study was to determine the accuracy of cine computed tomography in the diagnosis of constrictive pericarditis. BACKGROUND: Constrictive pericarditis is characterized by abnormalities of both cardiac structure and function. Accurate diagnosis requires detection of both a thickened pericardium and abnormal ventricular diastolic filling. At present, no one diagnostic technique has demonstrated sufficient accuracy in this setting. Cine computed tomography is a relatively new cardiac imaging mode with very high time and spatial resolution that has the potential to accurately diagnose constrictive pericarditis. METHODS: Twelve consecutive patients were retrospectively identified who had catheterization findings suggestive of constrictive physiology, had undergone a cine computed tomographic examination and had pathologic data that delineated the status of the pericardium. Group 1 (with constrictive pericarditis; n = 5) had surgical confirmation of thickened pericardium and improved clinically after pericardiectomy. Group 2 (no constrictive pericarditis; n = 7) had cardiomyopathy with normal pericardium. Seven normal volunteers (Group 3) were also studied. Cine computed tomograms were obtained for the entire heart (8-mm slices, 17 frames/s, nonionic contrast medium). Pericardial thickness was measured at 10 degrees intervals at three ventricular levels in each subject. The rapidity of diastolic filling was assessed by calculating the percent filling fraction in early diastole. RESULTS: Pericardial thickness was 10 +/- 2 mm (mean +/- SD) in Group 1, 2 +/- 1 mm in Group 2 and 1 +/- 1 mm in Group 3 (p < 0.05, constrictive pericarditis vs. no constrictive pericarditis). Left ventricular filling fraction was 83 +/- 6% in Group 1, 62 +/- 9% in Group 2 and 44 +/- 5% in Group 3. Right ventricular filling fraction was 93 +/- 5% in Group 1, 62 +/- 14% in Group 2 and 35 +/- 6% in Group 3 (p < 0.05, Group 1 vs. Groups 2 and 3). Both indexes provided a clear-cut distinction between patients with and without constriction. CONCLUSIONS: Cine computed tomography simultaneously provides both anatomic and physiologic data that allow accurate preoperative diagnosis of pericardial constriction.
The presence or absence of ureteral peristalsis was noted during real-time sonography of 61 dilated ureters in children. The findings were correlated with diagnoses established using standard radiographic and radionuclide imaging techniques. Of the 47 dilated ureters that exhibited peristalsis 44 were classified as not obstructed when assessed with standard imaging and functional studies. The most frequent etiology for ureteral dilatation associated with peristalsis was high grade vesicoureteral reflux (31 ureters). Three peristaltic ureters were shown to be mildly to moderately obstructed. Absence of peristalsis was noted in 14 ureters: 13 were severely obstructed, while in 1 the involved kidney had no function. In the pediatric age group the demonstration of peristalsis in a dilated ureter is frequently associated with vesicoureteral reflux and is seldom associated with obstruction. Obstruction, if present, usually is mild. Aperistaltic ureterectasis implies severe obstruction or poor renal function.
Previous studies from our laboratory demonstrated that 8 weeks after the induction of diabetes by the administration of streptozotocin (STZ) there was a downregulation of beta adrenergic and muscarinic cholinergic receptors in rat prostate, and that early insulin treatment (started 3 days after the onset of diabetes) prevented these alterations from occurring. In the present study, the effects of later insulin treatment (started 8 weeks after the onset of diabetes) on the reversibility of diabetes-induced alterations in beta adrenergic and muscarinic receptors in rat prostate were investigated. Three groups of rats were maintained for 16 weeks: 1) diabetics, 2) insulin-treated diabetics (subcutaneously injected with 5 to 8 U per day starting 8 weeks after the onset of diabetes) and 3) age matched controls. Binding studies with [3H]dihydroalprenolol (DHA) and [3H]quinuclidinyl benzilate (QNB) showed a significantly lower density of beta adrenergic and muscarinic cholinergic receptors in the diabetic rat prostate than in prostate from either controls or insulin-treated diabetic animals. Inhibition of [3H]DHA binding by isoproterenol, a beta adrenergic agonist, and binding of [3H]QNB by carbachol, a muscarinic agonist, indicated the presence of low and high affinity agonist binding sites for each receptor. The relative proportion of high affinity to total binding sites as well as the low and high affinity constants were similar in all groups. These data indicate that insulin treatment, begun 8 weeks after the onset of diabetes, can reverse the diabetes-induced downregulation of both beta adrenergic and muscarinic cholinergic receptors in STZ-diabetic rat prostates.
In animals, sympathetic responses to orthostasis are regulated in part by cardiopulmonary afferents arising from atrial and ventricular baroreceptors. To determine the relative importance of these baroreceptor regions in the cardiopulmonary baroreflex of normal humans, simultaneous measurements of left atrial and right and left ventricular volumes (cine computed tomography), invasive hemodynamics, forearm vascular resistance (plethysmography), and efferent sympathetic nerve activity to muscle (microneurography) were obtained under control conditions and with nonhypotensive lower body negative pressure (-10 mmHg, LBNP-10) in nine normal human subjects. LBNP-10 did not alter heart rate or mean systemic arterial pressure, but it did produce significant decreases in pulmonary artery diastolic and right atrial pressures. This reduction in cardiac filling pressures resulted in efferent sympathoexcitation evidenced by increases in forearm vascular resistance and efferent sympathetic nerve activity to the muscle. LBNP-10 did not alter end-diastolic volume of the left or the right ventricle. Similarly, ventricular stroke volume was unchanged during LBNP-10, as assessed by cine computed tomography or thermodilution techniques. In contrast, LBNP-10 resulted in a significant decrease in left atrial volume. Thus, LBNP produced a significant decrease in cardiac filling pressures and left atrial volumes with resultant reflex sympathoexcitation, whereas ventricular volumes were unchanged. These observations suggest an important role for left atrial (nonventricular) baroreceptor afferents in the cardiopulmonary baroreflex of normal humans.