Search PubMed⌕ Search

Biomedical subjects

W R Bauer

Publications and source records attributed to W R Bauer.

At least 37 records · Page 2Linked to original sources

The relationship between the BOLD-induced T(2) and T(2)(*): a theoretical approach for the vasculature of myocardium.

Recently the blood oxygenation level-dependent (BOLD)-related T(2)* of myocardium was derived as an analytical function of intracapillary blood volume, blood oxygenation, and nuclear spin diffusion. The basis of this approach was to approximate the diffusion-induced field fluctuations a nuclear spin is subjected to by strong collision dynamics, i.e., the field fluctuations are uncorrelated. The same analysis is now performed for spin echo experiments that gives myocardial T(2) as a function of the parameters above and the echotime. An analytical relationship between T(2) and T(2)* relaxation is derived. The dependence of T(2) on diffusion, echo time, and blood oxygenation is congruent with simulation and experimental data. Magn Reson Med 42:1004-1010, 1999.

Animals↗

BOLD-MRI in ten patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery.

Changes of myocardial oxygenation can be studied by measurements of the apparent transverse relaxation time T2*, which is correlated with the oxygenation state of hemoglobin. In this study, ten patients with coronary artery disease (CAD) underwent blood oxygenation level dependent (BOLD) T2* measurements using a segmented gradient echo pulse sequence with ten echoes. T2* measurements were performed in a single short-axis slice of the heart at rest and under pharmacological stress with dipyridamole (DIP), which increases myocardial blood flow. For comparison, all patients underwent X-ray angiography and stress-echocardiography within 4 days after the MR exam. In one patient, MR examination was repeated 10 weeks after percutaneous transluminal coronary angioplasty (PTA). In the differential T2* maps, expected ischemic areas of myocardium were identified in six patients. In these regions, T2+ values (30 +/- 8 ms) were significantly reduced when compared to the remaining myocardium (48 +/- 9 ms, P < 0.01). In four patients, the myocardial region of interest could not be assessed owing to severe susceptibility artifacts in the ischemic region. The success of the PTA treatment could be visualized from a more homogeneous DIP induced increase in T2* within the ischemic myocardium (from 26 +/- 1 to 29 +/- 1 ms before PTA versus 26 +/- 1 to 31 +/- 4 ms after PTA, P < 0.001).

Adult↗

Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse.

The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.

Animals↗

Quantitative regional blood volume studies in rat myocardium in vivo.

Many pathophysiological processes in the myocardium are in close relation to changes of the regional blood volume and regional myocardial blood flow or perfusion. Only few methods exist to obtain quantitative values for these parameters. Quantitative regional blood volume (RBV) studies in rat myocardium are presented using snapshot fast low angle shot (FLASH) inversion recovery T1 measurements with two different blood pool contrast agents, gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA) albumin and Gd-DTPA polylysine. In contrast to previous attempts, each snapshot FLASH image acquisition was ECG-triggered under breathhold conditions. To measure relaxation times shorter than a heart cycle, each T1 sequence was repeated two times with different delays between inversion pulse and first image acquisition. The experiments were performed on a Bruker Biospec 70/21 using a homogeneous transmitter coil and a circularly polarized surface receiver coil, a special ECG trigger unit, and a respirator that is controlled by the pulse program. Based on a fast exchange model RBVm maps were calculated from the relaxation time maps for different concentrations of the two blood pool contrast agents. A significant dependence of the RBVm values on blood T1 was found. This is in accordance with a model that has been developed recently relating the dependence of RBVm on T1 of blood to perfusion. For Gd-DTPA albumin, the application of the model to the experimental data yields realistic values for RBV and perfusion. The values, which are in accordance with literature data, were obtained at highest contrast agent concentrations i.e., lowest relaxation times of blood (ca. 200 ms).

Albumins↗

The effect of perfusion on T1 after slice-selective spin inversion in the isolated cardioplegic rat heart: measurement of a lower bound of intracapillary-extravascular water proton exchange rate.

Many NMR measurements of cardiac microcirculation (perfusion, intramyocardial blood volume) depend on some kind of assumption of intracapillary-extravascular water exchange rate, e.g., fast exchange. The magnitude of this water exchange rate, however, is still unknown. The intention of this study was to determine a lower limit for this exchange rate by investigating the effect of perfusion on relaxation time. Studies were performed in the isolated perfused cardioplegic rat heart. After slice-selective inversion, the spin lattice relaxation rate of myocardium within the slice was studied as a function of perfusion and compared with a mathematical model which predicts relaxation rate as a function of perfusion and intracapillary-extravascular exchange rate. A linear relationship was found between relaxation rate T(-1) and perfusion P normalized by perfusate/tissue partition coefficient of water, lambda: deltaT(-1) = m x deltaP/lambda with 0.82 < or = m < or = 1.06. Insertion of experimental data in the model revealed that a lower bound of the exchange rate from intra- to extravascular space is 6.6 s(-1) (4.5 s(-1), P < 0.05), i.e., the intracapillary lifetime of a water molecule is less than 150 ms (222 ms, P < 0.05). Based on this finding, the T1 mapping after slice-selective inversion could become a valuable noncontrast NMR method to measure variations of perfusion.

Animals↗

Study of microcirculation by coloured microspheres and NMR-microscopy in isolated rat heart: effect of ischaemia, endothelin-1 and endothelin-1 antagonist BQ 610.

Although the investigation of coronary microcirculation is of great importance, available methods have severe restrictions. They do not allow the study of vasodynamics of resistance vessels and microscopic conductance vessels simultaneously in the isolated beating rat heart. We now demonstrate that the combined measurement of perfusion which reflects the state of resistance vessels and cross-sections of microscopic conductance vessels is feasible in the model of the isolated constant flow perfused rat heart. Perfusion measurement was based on injection of coloured microspheres. Cross-sections of microscopic conductance vessels (diameter >140 micron) were determined by NMR-microscopy by flow weighted imaging. Both methods were established recently by our group. The combined measurement was applied to hearts which were subjected to ischaemia and reperfusion (group 1: n=5, 15 min ischaemia/group 2: n=7, 30 min ischaemia/measurements before ischaemia and 15/30 min after reperfusion), 200 pmol endothelin-1 bolus application (group 3: n=6/measurements before and 5 min after drug application), continuous infusion of the endothelin-1 antagonist BQ 610 (group 4: n=6/measurements before and 20 min after onset of infusion), and 200 pmol endothelin-1 application superimposed on 20 min of continuous BQ 610 infusion (group 5: n=7/combined measurement before BQ 610 infusion and 5 min after endothelin-1 application). In group 1, 15 min reperfusion restored the pre-ischaemic perfusion state, whereas conductance vessels were dilated (80.8+/-2.6%), after 30 min reperfusion pre-ischaemic conditions were also restored for conductance vessels. In group 2, a redistribution of perfusion from left ventricular endocardium to the right ventricular wall was observed. Post-ischaemic rhythm disturbances made NMR-imaging in this group impossible. In group 3, a shift of perfusion from the left ventricular myocardium to the right ventricular wall was observed. Similarly, the cross-section of left ventricular conductance vessels decreased (-32.6+/-2.1%), whereas size of right ventricular vessels increased. In group 4, BQ 610 had no effect on perfusion nor on vessel size and antagonized the effect of endothelin-1 on perfusion and vessel size in group 5.

Animals↗

Twist, writhe, and geometry of a DNA loop containing equally spaced coplanar bends.

The formation of a topologically closed DNA loop is important in many biological processes, including the regulation of transcription, recombination, and replication. Modeling DNA as an isotropic elastic rod, we use finite element analysis to show that the dependence of the twist (delta Tw) and the writhe (Wr) upon the linking number deficit (delta Lk) is strongly influenced by intrinsic bends. We determine how the geometry of a DNA loop changes as a function of the number of uniformly spaced coplanar 20 degrees bends, oriented so as to open toward the center of the loop. We also calculate the geometry of DNA rods that are smoothly bent to the same extent. The response of both delta Tw and Wr of a bent DNA to changes in delta Lk falls into one of three categories, depending upon the number of bends. For a single bend of 20 degrees, Wr increases monotonically with delta Lk and the change in delta Tw with distance is constant along the entire DNA axis. For two to ten 20 degrees bends, Wr passes first through a local maximum, then through a local minimum, and finally increases monotonically as delta Lk increases. For eleven to eighteen 20 degrees bends, Wr again varies monotonically with delta Lk. For all numbers of bends greater than two, the delta Tw per unit length depends upon the distribution of intrinsic bends, being constant between any two adjoining bends but varying with their position relative to the cut location. Accompanying these delta Lk-associated changes in Wr and delta Tw per unit length are characteristic changes in geometry that are specific for each category. The results of these calculations raise the possibility that intrinsic bends can serve as a control factor in the biological functions associated with loop formation in DNA.

DNA↗

Magnetization exchange in capillaries by microcirculation affects diffusion-controlled spin-relaxation: a model which describes the effect of perfusion on relaxation enhancement by intravascular contrast agents.

The effect of perfusion on relaxation time in tissue has only been considered for first-pass kinetics of NMR-signal after application of contrast agents. The importance of perfusion on relaxation has not yet been studied for steady state conditions, i.e., when the intravascular relaxation rate is constant in time. The aim of this study is to develop a model in which T1 relaxation is derived as a function of perfusion and intracapillary volume fraction (regional blood volume). Tissue is considered to be two-compartment system, which consists of intracapillary and extravascular space. Intracapillary relaxation differs from relaxation in the arterial system due to diffusion-exchange of magnetization from extravascular to intracapillary space. Perfusion tends to attenuate this difference and thus counteracts the effect on intracapillary relaxation. Relaxation in the extravascular and intracapillary magnetization are linked by diffusion. This dependence is presented in analytical form and a generic equation is derived. AT1 experiment is considered in which all spins of tissue and blood are inverted at the beginning. Calculations are performed for the fast exchange model of tissue. Perfusion increases relaxation enhancement of intravascular contrast agents. This effect is considerable in highly perfused tissue like myocardium. The dependence of relaxation on perfusion implies an overestimation of the regional blood volume when the calculation of the latter is based on tissue models that neglect perfusion. The model presented here is applied to predict the effect of perfusion on T1 imaging with FLASH-pulse sequences because this technique has been proven to be a powerful method to obtain T1 maps within a short time interval. For the fast exchange model, two algorithms are suggested that determine perfusion and regional blood volume from T1 imaging in the presence and absence of intravascular contrast agents.

Blood Volume↗

In vivo colored microspheres in the isolated rat heart for use in NMR.

Myocardial perfusion measurement with colored microspheres may become an alternative for radioactive microsphere techniques. We use and validate a spectrophotometric method that has been previously established for large animals in the isolated perfused rat heart. The perfusion system was adapted for use in a NMR microscope. Hearts were perfused with constant coronary flow that was adjusted to a coronary perfusion pressure of 100 mmHg. Homogeneous coronary inflow of microspheres was represented by equal distribution of microspheres of two different colors after simultaneous injection. Mean regional myocardial blood flow was 17.76 +/- 5.01 ml/min/g, mean wet heart weight was 1.13 +/- 0.34 g and mean global flow was 20.06 +/- 0.60 ml/min. Heart rate was 296 +/- 8.9 beats/min and left ventricular pressure was similar 5 min before (149.1 +/- 14.27 mmHg) and after (147.1 +/- 13.49 mmHg) microsphere injection. Microspheres of four colors that were injected sequentially, at various coronary flows, demonstrated linearity and reproducibility of the technique. A cumulative use of less than 90 000 microspheres showed no effect on hemodynamics especially on left ventricular pressure.

Animals↗

Energetics of coupled twist and writhe changes in closed circular pSM1 DNA.

The extent of local denaturation in closed circular pSM1 DNA depends upon the linking difference, delta Lk, and the temperature, t. We have determined the denaturation profiles, using gel electrophoresis, over the ranges -37 < or = delta Lk < or = +16 and 25 degrees C < or = t < or = 65 degrees C. We have applied statistical mechanical methods to these data to evaluate the free energies of superhelix formation, of the twisting of single strands around each other, and of the initration of local denaturation. Because the complete nucleotide sequence is needed for this analysis, the complete pSM1 DNA sequence was determined and is reported here. The values of the free energy parameters found in this work agree closely with those previously obtained from experiments with pBR322 DNA, suggesting that there is little dependence of these values on the particular DNA sequence. We find the temperature dependence of these free energies by the appropriate statistical mechanical analysis of the temperature-dependent denaturation profiles produced by supercoiling. Calculations of the transition probability profiles indicate that the course of local denaturation in pSM1 DNA involves a complex competition among several sites of comparable susceptibility. This contrasts with the melting of pBR322 DNA, in which one principal site dominates. In both molecules the sites of predicted denaturation occur at or near regulatory regions, suggesting that duplex destabilization may be associated with their biological activities.

Base Sequence↗

Investigation of coronary vessels in microscopic dimensions by two- and three-dimensional NMR microscopic imaging in the isolated rat heart. Visualization of vasoactive effects of endothelin 1.

BACKGROUND: Nuclear magnetic resonance (NMR) imaging of macroscopic coronary vessels is rapidly advancing, whereas little attention has focused on development of NMR techniques for investigation of coronary microvessels. Such techniques would be of particular importance, since conventional methods to visualize coronary microvessels have specific limitations. The aim of our study was to develop two- and three-dimensional (2D and 3D) high-resolution imaging of coronary microvessels. Quantitative analysis of vessel size was performed in tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1. METHODS AND RESULTS: Angiographic imaging was performed on an 11.75-T magnet by 2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this method in providing correct vessel size was tested by phantom experiments. Experiments were carried out in the isolated constant-pressure-perfused rat heart with continuous registration of coronary flow and left ventricular pressure. NMR pulse sequences were pressure-triggered in mid diastole. Four groups of hearts were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the long axis of the heart was performed. Cross sections of vessels with diameter > 140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n = 13), tomograms perpendicular to the long axis were obtained before and after administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3). Vehicle had no effect on vessel cross section. Endothelin 1, which decreased global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak but, on average, significant inverse correlation between area of cross section and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7 normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the entire coronary artery tree was obtained, revealing excellent agreement with anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery was demonstrated. CONCLUSIONS: Visualization and quantification of coronary microvessels are feasible by NMR microscopy. NMR microscopy bears the potential of becoming a powerful tool for the investigation of the coronary microcirculation.

Animals↗

Chirality and surface twist of DNA wrapped on protein surfaces.

The surface twist, STw, is a measure of the component of duplex twist associated with the trajectory of the DNA axis wrapped on a protein surface. We calculate STw for various surfaces of revolution, including the cylinder and truncated paraboloid, ellipsoid, and hyperboloid of revolution. We show that the sign of STw cannot be stated unequivocally from knowledge of the chirality of the wrapping but depends also upon the nature of the wrapping (protein) surface. We define and discuss three geometric classes. Class (1) includes the cylinder, certain types of convex paraboloids, all concave paraboloids, the prolate ellipsoid, and the hyperboloid; here STw > 0 for right-handed wrapping and STw < 0 for left-handed wrapping. Class (2) is the sphere, for which STw = 0 for both types of handedness. Case (3) includes oblate ellipsoids and some regions of convex paraboloids; here STw < 0 for right handed wrapping and STw > 0 for left-handed wrapping.

DNA↗

[An unusual series of complications in therapy with implantable cardioverter-defibrillator].

A 48-year-old man with dilative cardiomyopathy and a history of resuscitation due to ventricular fibrillation received an implantable cardioverter-defibrillator (ICD) with epicardial sensing and defibrillation electrodes in March 1990. An early battery depletion due to increased electrical leakage of a filter capacitor necessitated a generator exchange in July 1990. Subsequent inappropriate discharges occurred, but no underlying cause could be documented by history, clinical examination, Holter monitoring, and beepograms. Only 3 months later was it possible to demonstrate oversensing by repeated beepograms, and a new generator and transvenous sensing electrode were implanted in October 1991. Four months later, inappropriate shocks were suspected again. Once more, history, clinical examination, Holter monitoring, and beepograms were without pathological result. At follow-up, repeated beepograms during exercise demonstrated an oversensing, and an insulation defect of the newly implanted sensing electrode close to the edge of the generator could be documented on x-ray. Since replacement of generator and sensing electrode in July 1992 the patient is doing well. He received two appropriate shocks which were associated with presyncope. ICD therapy is very complex and therefore should only be performed in centers providing the necessary personal, apparative and logistic conditions.

Death, Sudden, Cardiac↗

Effects of postnatal blockage of cortical activity with tetrodotoxin upon lesion-induced reorganization of vibrissae-related patterns in the somatosensory cortex of rat.

Previous studies have shown that postnatal blockade of thalamocortical activity with either tetrodotoxin (TTX) or the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV) does not prevent the formation of vibrissae-related patterns. In the present study, blockade of cortical activity with TTX was combined with ablation of a row of vibrissae follicles or transection of the infraorbital nerve (ION, the trigeminal nerve branch that supplies the vibrissae follicles) to determine whether the cortical reorganization that follows these lesions in otherwise untreated animals was dependent upon neuronal activity that could be blocked with TTX. The results demonstrated that cortical TTX implants had no quantitative or qualitative effects upon the cortical reorganization that followed either vibrissae follicle cauterization or ION transection.

2-Amino-5-phosphonovalerate↗

Nucleosome structural changes due to acetylation.

We have measured the helical repeat of acetylated nucleosomes reconstituted with HeLa cell histone octamers and the 5 S RNA gene positioning sequence from Xenopus borealis. The hydroxyl radical footprinting experiments show that the helical repeat of nucleosome-bound DNA is unchanged upon acetylation, and that the extent of DNA-protein contacts remains unaltered. These results, combined with previous determinations of the linking number change in minichromosomes as a function of the extent of acetylation, are analyzed with surface linking theory. We demonstrate that the shape of the nucleosome changes upon acetylation, in such a way as to decrease the number of times the DNA winds around the nucleosome central axis.

Acetylation↗

Interrelation of coronary effects of atrial natriuretic peptide and the renin-angiotensin system in the isolated perfused rat heart.

The coronary vascular effect of atrial natriuretic peptide is controversial: Coronary vasodilator as well as constrictor effects have been reported. The controversy may originate from interference of atrial natriuretic peptide with the renin-angiotensin system and/or tachyphylaxis of the effect of atrial natriuretic peptide. The effect of alpha-human atrial natriuretic peptide bolus application on changes of coronary flow was examined in the isolated, constant-pressure perfused rat heart. Six groups were considered: (1) control group; groups in which the renin-angiotensin system was modulated by pretreatment with continuous infusion of: (2) angiotensin II, (3) the angiotensin converting enzyme inhibitor captopril (4) the angiotensin II receptor blocker saralasin; and groups in which tachyphylaxis was examined by pretreatment with ANP, (5) as continuous infusion and (6) as bolus application. First, in control hearts, dose-response curves were obtained for single ANP dosages of 1-100 nmol. The effect of high dosages (40 and 100 nmol) was biphasic, with an initial vasodilator and subsequent long-lasting vasoconstrictor component. Hearts in which coronary flow was reduced by approximately 18% through continuous angiotensin II infusion showed an enhanced early vasodilator response after ANP administration, whereas the vasoconstrictor effect was no longer observable. Angiotensin converting enzyme inhibition and angiotensin II receptor blockade reduced the vasodilator effect of ANP. In addition, saralasin nearly abolished ANP-induced vasoconstriction, whereas vasoconstriction was unaltered by pretreatment with captopril. Captopril or saralasin alone did not change coronary flow, heart rate and left ventricular developed pressure. In groups (5) and (6). ANP bolus application showed significantly reduced vasomotor activity. We conclude that in the isolated rat heart. ANP has a biphasic effect with early vasodilation and late vasoconstriction. Both effects can be modulated by inhibition of the renin-angiotensin system at different levels indicating that vasomotor ANP effects result from interaction of ANP with the local renin-angiotensin system. ANP effects can be markedly reduced by tachyphylaxis.

Angiotensin II↗