Search PubMed⌕ Search

Biomedical subjects

W L Rogers

Publications and source records attributed to W L Rogers.

At least 37 records · Page 2Linked to original sources
PubMed1993

Systemic hemodynamics, renal function and hormonal levels during inhibition of neutral endopeptidase 3.4.24.11 and angiotensin-converting enzyme in conscious dogs with pacing-induced heart failure.

The systemic hemodynamic, renal and hormonal responses to SQ 28,603 (N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta-alanine) the selective inhibitor of neutral endopeptidase 3.4.24.11, the angiotensin-converting enzyme inhibitor captopril and their combination were determined in conscious dogs after 1 or 3 weeks of rapid ventricular pacing. Coadministration of captopril (100 or 10 mumol/kg i.v.) and SQ 28,603 (10 mumol/kg i.v.) significantly reduced mean arterial pressure, systemic vascular resistance and renal vascular resistance and increased cardiac output, stroke volume and renal blood flow in the conscious dogs paced for 1 week. This pattern of hemodynamic improvement was not predicted by the activity of the individual inhibitors. The combination of inhibitors did not significantly increase sodium excretion because of the variability introduced by the depressor activity; however, the pressure-natriuresis curve was steeper and shifted leftward, indicating that sodium excretion was maintained at lower renal perfusion pressures. The increases in urinary and plasma levels of cyclic GMP and atrial natriuretic peptide stimulated by SQ 28,603 were not affected by captopril. The data indicated that the hemodynamic and renal responses produced by SQ 28,603, presumably by elevating atrial natriuretic peptide levels, were enhanced by suppression of angiotensin II or that the combination of inhibitors protected other vasodilator/natriuretic peptides from degradation. Qualitatively similar responses to SQ 28,603, captopril and the combination of inhibitors were obtained in dogs paced for 3 weeks. In summary, the combined angiotensin-converting enzyme and neutral endopeptidase 3.4.24.11 inhibitors improved systemic hemodynamics and maintained renal function in conscious dogs with pacing-induced heart failure.

Alanine↗
PubMed1992

Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.

The depressor, natriuretic and cyclic GMP responses to several species of brain natriuretic peptide (BNP) were compared to atrial natriuretic peptide (ANP) 99-126 in conscious spontaneously hypertensive rats (SHR) and in conscious cynomolgus monkeys treated with vehicle or the selective neutral endopeptidase (NEP 3.4.24.11) inhibitor N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta- alanine (SQ 28,603). In the conscious SHR, the natriuretic and cyclic GMP responses to 3 nmol/kg i.v. rat BNP-32 greater than rat ANP 99-126 greater than pig BNP-26 and were significantly potentiated by 100 mumol/kg i.v. SQ 28,603. Human BNP-32 was inactive in the SHR treated with either vehicle or SQ 28,603. In contrast, 1 nmol/kg i.v. of human BNP-32 stimulated renal and depressor responses in the conscious monkeys that were greater than or equal to those elicited by human ANP 99-126, whereas 3 nmol/kg i.v. rat BNP-32 reduced mean arterial pressure without affecting renal function. Furthermore, SQ 28,603 (100 mumol/kg, i.v.) significantly enhanced the cumulative losses of sodium and cyclic GMP stimulated by each of these peptides. In conclusion, the renal and depressor activities of BNP are highly species specific and are significantly potentiated by an inhibitor of NEP 3.4.24.11 in conscious SHR and monkeys. Therefore, protection of endogenous BNP may contribute importantly to the activity of NEP 3.4.24.11 inhibitors in cardiorenal disorders such as hypertension and congestive heart failure.

Alanine↗
PubMed1992

Technetium-99m-N1-(2-mercapto-2-methylpropyl)-N2-(2-propargylthio-2- methylpropyl)-1,2-benzenediamine (T691): preclinical studies of a potential new tracer of regional cerebral perfusion.

We report in vitro and in vivo preclinical studies of a new cerebral blood flow tracer, [99mTc]N1-(2-mercapto-2-methyl-propyl)-N2-(2- propargylthio-2-methylpropyl)-1,2-benzenediamine (T691). The tracer demonstrates excellent in vitro chemical stability and accumulates regionally in the brain in a pattern consistent with that of cerebral blood flow. First-pass cerebral extraction determined with the use of the brain uptake index method in the rat was 0.76. Bolus intracarotid injection in monkeys indicated a cerebral extraction of 68% and prolonged retention of 67% of the initially extracted activity. Autoradiographic studies in rats revealed a pattern characteristic of cerebral blood flow at both 1 and 60 min after systemic injection. Dynamic tomographic imaging following systemic injection in the monkey revealed peak brain activity 1 to 2 min postinjection, without significant decline over 60 min. Chromatographic studies of brain as long as 60 min following systemic injection of [99mTc]T691 showed no evidence of tracer metabolism to account for its retention. Overall, [99mTc]T691 demonstrates promise as a potential new clinical tracer of cerebral perfusion.

Animals↗
PubMed1991

Testing of local gamma-ray scatter fractions determined by spectral fitting.

The spectral-fitting method of correction for gamma-ray Compton scattering within objects separates the unscattered and scattered components of locally measured energy spectra. Here, we employ a third-order polynomial for the scattering and an approximately constant fitting window. A scatter fraction, defined as total scattered over total unscattered counts within a 20% window, is calculated for each point in our Anger camera images. These scatter fractions are tested against those from Monte-Carlo simulation for 99mTc and against results from semiconductor detector measurements for 131I. A radioactive sphere at several locations within a non-radioactive cylinder and the inverse are imaged for the testing. For one case, reproducibility of the spectral-fitting scatter fraction as a function of the number of unscattered counts within the 20% acceptance window was also determined. With 99mTc, for all cases, the agreement between spectral fitting and the standard estimation method is within 16%. With 131I, for the 'hot' sphere at two locations, the agreement is within 21%. For the 'hot' sphere at the third location (off the cylinder axis towards the camera), the dependence of scatter fraction on transverse distance is good although the absolute values are too large. Scatter fraction reproducibility is within 10% for 1000 or more counts. Therefore, further testing of spectral fitting and initial application to realistic clinical images seem to be in order.

Gamma Cameras↗
PubMed1991

Antihypertensive and renal activity of SQ 28,603, an inhibitor of neutral endopeptidase.

SQ 28,603 is a potent and selective inhibitor of neutral endopeptidase 3.4.24.11 (NEP), an enzyme that degrades atrial natriuretic peptide (ANP). In conscious deoxycorticosterone acetate (DOCA)/salt hypertensive rats, 300 mumol/kg, i.v., of SQ 28,603 significantly lowered mean arterial pressure (MAP) from 177 +/- 12 to 154 +/- 8 mm Hg and increased urinary cyclic guanosine monophosphate (GMP) excretion from 204 +/- 70 to 1,068 +/- 326 pmol/kg/min within 2 h. Urinary sodium excretion increased within 20 min from a control 51.2 +/- 17.3 to 102.1 +/- 26.7 muEq/kg/min. Infusion of SQ 28,603 (3.7 mumol/kg/min) for 6 h in a separate group of conscious DOCA/salt hypertensive rats gradually reduced MAP from 180 +/- 7 to 142 +/- 7 mm Hg and increased urinary cyclic GMP excretion from 182 +/- 36 pmol/kg/min to 1,009 +/- 394 pmol/kg/min. Despite the continuous infusion of the inhibitor, the natriuretic response peaked during the first hour of treatment at 128 +/- 18 muEq/kg/min (vehicle = 54 +/- 10 muEq/min). Plasma ANP was significantly greater in the rats infused with SQ 28,603 than in those receiving vehicle (333 +/- 108 and 98 +/- 14 fmol/ml, respectively). SQ 28,603 also significantly reduced NEP activity by 95% in the kidneys (1.28 +/- 0.08 vs. 18.35 +/- 0.61 mumol/min after SQ 28,603 and vehicle respectively) and by 77% in the lungs (0.29 +/- 0.03 vs. 0.92 +/- 0.14 mumol/kg after SQ 28,603 and vehicle, respectively). In conclusion, inhibition of NEP activity by SQ 28,603 significantly decreased MAP and increased plasma ANP concentrations and urinary excretion of cyclic GMP in conscious DOCA/salt hypertensive rats.

Alanine↗
PubMed1991

Heart failure augments the cardiovascular and renal effects of neutral endopeptidase inhibition in rats.

We compared the cardiovascular and renal actions of the neutral endopeptidase (NEP) inhibitor, SQ 28,603, in normal rats and in rats with healed myocardial infarcts. The infarcted rats were studied in the conscious state 8 weeks after ligation of the left main coronary artery and 4 h after placement of cardiovascular and renal catheters. Infarct size was 39 +/- 1.2% of left ventricle circumference; right ventricle and lung weight to body weight ratios were twice those of normal rats. These postmortem values were shown to be associated with elevated left ventricular end diastolic pressure and high plasma atrial natriuretic peptide (ANP) concentration in separate groups of rats. SQ 28,603 at 100 mumol/kg intravenously (i.v.) caused urine volume and sodium excretion to increase by 79 +/- 11 microliters/min and 8.2 +/- 1.4 microEq/min, respectively, 20 min after injection in infarcted rats; these changes were significantly greater than those in normal rats (12 +/- 5 microliters/min and 1.6 microEq/min, respectively). Thoracic venous pressure decreased by 1.9 +/- 0.4 mm Hg 80 min after SQ 28,603 in infarcted rats and by only 0.1 +/- 0.1 mm Hg in normal rats (p less than 0.05 vs. infarcted rats). SQ 28,603 had no effects on mean arterial pressure (MAP), cardiac output (CO), or glomerular filtration rate (GFR). The observation that NEP inhibition has more pronounced effects in animals with high ambient ANP level than in those with normal ANP is consistent with previous studies in a variety of animal models and supports the concept that NEP inhibition potentiates endogenous ANP.

Alanine↗
PubMed1991

Evaluation of SQ 28,603, an inhibitor of neutral endopeptidase, in conscious monkeys.

The potent neutral endopeptidase inhibitor SQ 28,603 (N-(2-(mercaptomethyl)-1-oxo-3-phenylpropyl)-beta-alanine) significantly increased excretion of sodium from 4.9 +/- 2.3 to 14.3 +/- 2.1 muequiv./min and cyclic 3',5'-guanosine monophosphate from 118 +/- 13 to 179 +/- 18 pmol/min after intravenous administration of 300 mumol/kg (approximately 80 mg/kg) in conscious female cynomolgus monkeys. SQ 28,603 did not change blood pressure or plasma atrial natriuretic peptide concentrations in the normal monkeys. In contrast, 1-h infusions of 3, 10, or 30 pmol.kg-1.min-1 of human atrial natriuretic peptide lowered blood pressure by -3 +/- 4, -9 +/- 4, and -27 +/- 3 mmHg (1 mmHg = 133.322 Pa), increased cyclic guanosine monophosphate excretion from 78 +/- 11 to 90 +/- 6, 216 +/- 33, and 531 +/- 41 pmol/min, and raised plasma atrial natriuretic peptide from 7.2 +/- 0.7 to 21 +/- 4, 62 +/- 12, and 192 +/- 35 fmol/mL without affecting sodium excretion. In monkeys receiving 10 pmol.kg-1.min-1 of atrial natriuretic peptide, 300 mumol/kg of SQ 28,603 reduced mean arterial pressure by -13 +/- 5 mmHg and increased sodium excretion from 6.6 +/- 3.2 to 31.3 +/- 6.0 muequiv./min, cyclic guanosine monophosphate excretion from 342 +/- 68 to 1144 +/- 418 pmol/min, and plasma atrial natriuretic peptide from 124 +/- 8 to 262 +/- 52 fmol/mL. In conclusion, SQ 28,603 stimulated renal excretory function in conscious monkeys, presumably by preventing the degradation of atrial natriuretic peptide by neutral endopeptidase.

Alanine↗
PubMed1991

Clinical SPRINT imaging. Preliminary results compared to conventional SPECT brain scanning using Tc-99m HMPAO.

We have performed initial clinical studies using the high resolution single photon ring tomograph (SPRINT) and Tc-99m HMPAO. To determine what additional anatomic detail can be depicted using this high resolution, dedicated head, multidetector SPECT device compared to conventional SPECT, six patients with stroke and one normal volunteer were imaged after the injection of 20 mCi Tc-99m HMPAO on a conventional rotating Anger gamma camera (GE-400AC), followed immediately by imaging on SPRINT. Imaging acquisition on the GE-400AC gamma camera was performed using 360 degrees rotation, 64 stops, at 30 sec/stop, yielding an average of 985,714 counts for a 10.0 mm thick slice. GE-400AC images were of good quality, having in-plane full width half maximum (FWHM) resolution of approximately 15 mm. SPRINT acquisition of image data was performed using both the high resolution and high sensitivity apertures, with data collection over 15 or 20 minutes of imaging time accumulating approximately 500,000 counts and 1,000,000 counts, respectively, from patients in a 10.0 mm thick slice, achieving an in-plane FWHM resolution of approximately 8 mm and 10 mm for the two apertures, respectively. Both image resolution and contrast for visualization of gray, white, and cerebral spinal fluid filled brain structures were improved using SPRINT compared with the GE-400AC. We conclude that SPRINT is well suited for brain imaging with Tc-99m HMPAO and is of particular value for applications demanding high resolution.

Adult↗
PubMed1990

Myocardial clearance kinetics of technetium-99m-SQ30217: a marker of regional myocardial blood flow.

SQ30217 is a new, technetium-99m-(99mTc) labeled perfusion agent introduced for cardiac imaging. To evaluate the myocardial tracer kinetics, 99mTc-SQ30217, was injected intracoronarily in open-chested dogs under baseline conditions and after administration of intravenous (i.v.) dipyridamole. Myocardial first-pass retention fraction averaged 0.90 +/- 0.04. Clearance of the tracer occurred in a biexponential manner. Sixty-seven percent of retained activity cleared with a half-time of 2.3 +/- 0.6 min, while the residual activity demonstrated slow clearance. The clearance rate of the rapid phase correlated with myocardial blood flow (r = 0.72, p less than 0.001). Myocardial SQ30217 clearance rate following i.v. injection as determined by dynamic imaging with tomography (SPRINT) averaged 21 +/- 4 min and increased to 13 +/- 4 min following dipyridamole. Thus, 99mTc-SQ30217 is a promising flow tracer with high initial myocardial retention and rapid tissue clearance, which allow repeated flow determinations within short time intervals using advanced SPECT technology.

Animals↗
PubMed1990

SPECT dual-energy-window Compton correction: scatter multiplier required for quantification.

The dual-energy window Compton-scattering correction technique is defined here especially for accurate quantification of focal regions having higher than average uptake. The quantification is relative to a known-activity reference source. The scatter multiplier ("k" value) is determined for a radioactive 99mTc sphere on or off the axis of a cylinder containing water with or without background. Both maximum likelihood and filtered-backprojection reconstruction are employed. Either projections or tomograms are corrected. With tight regions of interest, there is a tendency for the requisite "k" value to be slightly lower as the diameter of the cylinder is increased. Neither sphere location nor background perturbs "k", however, so a constant value is a good, first approximation. Then a two-sphere validation test yields an accuracy of 8% with subtracted-tomograms ("k" = 1.30) and 2% with subtracted-projections ("k" = 1.20). With a reference-source region of interest which is four times larger, "k" is reduced and also now depends on background. Although equivalent quantitatively, maximum likelihood is preferable to filtered backprojection with Chang attenuation correction since it produces a less-noisy image.

Algorithms↗
PubMed1988

SPECT Compton-scattering correction by analysis of energy spectra.

The hypothesis that energy spectra at individual spatial locations in single photon emission computed tomographic projection images can be analyzed to separate the Compton-scattered component from the unscattered component is tested indirectly. An axially symmetric phantom consisting of a cylinder with a sphere is imaged with either the cylinder or the sphere containing 99mTc. An iterative peak-erosion algorithm and a fitting algorithm are given and employed to analyze the acquired spectra. Adequate separation into an unscattered component and a Compton-scattered component is judged on the basis of filtered-backprojection reconstruction of corrected projections. In the reconstructions, attenuation correction is based on the known geometry and the total attenuation cross section for water. An independent test of the accuracy of separation is not made. For both algorithms, reconstructed slices for the cold-sphere, hot-surround phantom have the correct shape as confirmed by simulation results that take into account the measured dependence of system resolution on depth. For the inverse phantom, a hot sphere in a cold surround, quantitative results with the fitting algorithm are accurate but with a particular number of iterations of the erosion algorithm are less good. (A greater number of iterations would improve the 26% error with the algorithm, however.) These preliminary results encourage us to believe that a method for correcting for Compton-scattering in a wide variety of objects can be found, thus helping to achieve quantitative SPECT.

Algorithms↗
PubMed1986

Pituitary localization of 3H-spiroperidol by an uptake/storage mechanism?

The lack of a pituitary imaging agent combined with the considerable clinical value for such an agent prompted an examination of 3H-spiroperidol (3HSp). Spiroperidol was selected for initial evaluation based on its high affinity for D2 receptors which are known to be present in the pituitary. A time course study of 3HSp concentration in rat pituitary and other tissues was conducted. Pituitary activity levels were found to be constant from 5 min to 4 h and were about 8 times levels in corpus striatum at 1 h. Blocking studies with (+) butaclamol and with unlabelled spiroperidol suggested the existence of both a D2 receptor mediated binding localization and a second uptake which is postulated to be an internalization process. Further studies involving ultracentrifugation of pituitary homogenates resulted in evidence for association of 3HSp with dense subcellular particles. 3HSp thus appears to be internalized by pituitary cells.

Animals↗
PubMed1986

Use of DES-treated rats as an animal model for assessment of pituitary adenoma imaging agents.

Prolactin (PRL) secreting pituitary adenomas are the most common type of pituitary tumors. An imaging agent which specifically localized in prolactinomas would be of considerable clinical value for both initial detection and also for monitoring the effects of dopamine agonist therapy. Tritiated spiroperidol (3HSp) was selected for initial evaluation as a possible imaging agent based on: demonstrated localization in the pituitary and demonstrated binding to human PRL-secreting tumor tissue. DES was implanted in Fischer F344 rats and induced prolactinoma formation was evidenced by increased pituitary weight, elevated serum PRL levels and by an increase in the proportion of PRL-secreting cells in the pituitary. 3HSp concentrations in pituitary and other tissues of DES-treated rats were assessed in female rats and correlation studies showed that a 5-fold increase in serum PRL was associated with a 6-fold increase in both pituitary weight and % dose/organ accumulation of 3HSp. The number of pituitary D2 receptors per mg of protein in tissue homogenates was similar in both normal and DES-treated females. A blocking study with (+)-butaclamol demonstrated a D2 receptor-mediated component to 3HSp localization. In summary, an animal model for prolactinoma was characterized. An assessment of 3HSp accumulation indicates that radiolabelled spiroperidol shows excellent potential for detecting PRL-secreting tumors of the pituitary.

Adenoma↗
PubMed1986

Development of a kit-form analog of metaiodobenzylguanidine.

The synthesis and evaluation of two radiopharmaceutical analogs of metaiodobenzylguanidine (MIBG) are described. Unlike MIBG, these analogs are rapidly and conveniently radioiodinated at room temperature in clinically applicable kit form. Radioiodinated 4-amino-3-iodobenzylguanidine (AIBG) for injection is synthesized in 20 min using IODO-GEN as the radioiodide oxidant and an anion exchange filter for purification. AIBG shows an affinity for the heart and adrenal medullae of dog and monkey similar to that of MIBG. In addition, AIBG shows improved selectivity for the adrenergic nerves of the heart as demonstrated by chemical sympathectomy studies. Tomographic images of the dog heart and planar images of the dog adrenal medullae were obtained using [123I]AIBG and [131I]AIBG, respectively. Planar images of the monkey heart using [131I]AIBG were similar in quality to those reported previously with [131I]MIBG. In view of the facile radiosynthesis of AIBG, a clinical evaluation of this new agent is warranted.

3-Iodobenzylguanidine↗
PubMed1985

omega-123I-hexadecanoic acid metabolic probe of cardiomyopathy.

The utility of omega-123I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40 degrees LAO projection after a standard dose of omega-123I-hexadecanoic acid. An elimination T1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients. Of the 16 patients, only 2 had distinctly abnormal omega-123I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which carnitine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, omega-123I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk.

Adolescent↗
PubMed1984

Performance evaluation of SPRINT, a single photon ring tomography for brain imaging.

SPRINT, a prototype single photon tomograph, has been designed primarily for high-resolution brain imaging in humans with I-123-labeled compounds such as iodoamphetamine, hydroxyiodopropyldiamine (HIPDM), and iodobenzene (IBZ). SPRINT uses a ring of stationary, discrete Nal detectors, and fan-beam sampling is accomplished with a rotating eight-slit aperture ring that acquires a complete projection set in 1/8 revolution. In-plane and cross-plane resolutions are 8mm and 10mm FWHM, respectively, measured on axis. Sensitivity with an 18% energy window is 1000 cprs per microCi/cc for Tc-99m in a 20 cm diameter phantom. A detailed evaluation of system performance has been completed, and preliminary human brain blood flow images have been obtained using HIPDM.

Brain↗
PubMed1984

Simulated ECT of the left ventricle using rotating slant-hole collimator and two camera positions.

Limited-angular-range tomography leads to an elongating distortion of the object in the direction of the z axis (perpendicular to the camera face). Two-view tomography appends to the usual data set another set of projections taken after the camera is rotated 90 degrees about an axis perpendicular to z. We investigated two-view tomography using a rotating-slant-hole collimator, 12 projections per view and the SMART iterative algorithm. Computer simulations extended previous results to include noise and attenuation. Phantoms imaged were the Au-rings in air and a ventricle phantom angled with respect to the z axis and placed in a water bath. Two-view results were generally superior compared to one-view results, were subject to some artifact in imaging defects, but could detect defects by looking at the differences between two sets of images, and were fairly insensitive to ventricle angulation. Therefore, two-view tomography has promise for thallium-type imaging.

Heart↗