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Biomedical subjects

A Meissner

Publications and source records attributed to A Meissner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Naloxone improves functional recovery of myocardial stunning in conscious dogs through its action on the central nervous system.

This study tests the hypothesis that naloxone, but not its quarternary salt, naloxone methiodide (which does not enter the central nervous system), improves recovery from myocardial stunning in conscious dogs. Twenty dogs were chronically instrumented for measurement of heart rate, left atrial, aortic and left ventricular pressure (LVP), LV dP x dtmax(-1) and myocardial wall thickening fraction (WTF). Regional myocardial blood flow was determined with coloured microspheres. Occluder around the left anterior descending artery (LAD) allowed induction of reversible LAD ischaemia. Each of the 20 dogs underwent two LAD ischaemic challenges. Experiments (performed on separate days, in crossover fashion) were: (i) 10 min of LAD occlusion after application of naloxone 63 microg kg(-1) or naloxone methiodide 63 microg kg(-1) and (ii) occlusion without naloxone or naloxone methiodide. WTF was measured at baseline and until complete recovery occurred. LAD ischaemia significantly reduced LAD WTF with (mean (SD) 54 (15)% lower than baseline) and without naloxone (55 (16)% lower than baseline), without significant haemodynamic differences. Between I to 30 min of reperfusion, WTF was significantly higher with naloxone (P < 0.05). There was no difference in WTF with or without naloxone methiodide. We conclude that naloxone improved recovery from myocardial stunning in conscious dogs, and that this was centrally mediated.

Animals↗
PubMed2001

Effects of thoracic epidural anesthesia with and without autonomic nervous system blockade on cardiac monophasic action potentials and effective refractoriness in awake dogs.

BACKGROUND: The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization. METHODS: The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters. RESULTS: Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected. CONCLUSIONS: This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.

Action Potentials↗
PubMed2000

Three-dimensional protein NMR TROSY-type (15)N-resolved (1)H(N)-(1)H(N) NOESY spectra with diagonal peak suppression.

An earlier two-dimensional NOESY experiment with diagonal peak suppression in the (1)H(N)-(1)H(N) region is extended to three dimensions by including (15)N evolution while maintaining the TROSY approach throughout. The technique suppresses all anti-TROSY resonances by appropriate pulse sequence elements and for large molecules at high fields possible semi- and anti-TROSY artifacts are further suppressed by virtue of much shorter transverse relaxation times for these components. The new technique is demonstrated using an (15)N-labeled protein sample, RAP 17-97 (N-terminal domain of alpha2-macroglobulin Receptor Associated Protein), in H(2)O at 500 MHz.

Carrier Proteins↗
PubMed2000

New techniques for the measurement of C'N and C'H(N) J coupling constants across hydrogen bonds in proteins.

Two new two- or three-dimensional NMR methods for measuring (3h)J(C'N) and (2h)J(C'H) coupling constants across hydrogen bonds in proteins are presented. They are tailored to suit the size of the TROSY effect, i.e., the degree of interference between dipolar and chemical shift anisotropy relaxation mechanisms. The methods edit 2D or 3D spectra into two separate subspectra corresponding to the two possible spin states of the (1)H(N) spin during evolution of (13)CO coherences. This allows (2h)J(C'H) to be measured in an E.COSY-type way while (3h)J(C'N) can be measured in the so-called quantitative way provided a reference spectrum is also recorded. A demonstration of the new methods is shown for the (15)N,(13)C-labeled protein chymotrypsin inhibitor 2.

Carbon↗
PubMed2000

Suppression of diagonal peaks in three-dimensional protein NMR TROSY-type HCCH correlation experiments.

A novel method for suppression of (13)C-(13)C diagonal peaks without sensitivity loss in three-dimensional HCCH TROSY-type NMR correlation experiments involving aromatic side chains in proteins (Pervushin et al., J. Am. Chem. Soc. 120, 6394-6400 (1998)) is presented. The key element is a spin-state-selective filter in the (13)C-(13)C mixing sequence with the dual effect of selecting the TROSY resonance in the preceding evolution period and interchanging TROSY and anti-TROSY resonances. The cross peaks are invariant to this filter but diagonal peak coherence gets concentrated on the anti-TROSY transition so that it can be eliminated by a (13)C --> (1)H TROSY transfer element. The new method is demonstrated using a (13)C,(15)N-labeled protein sample, RAP 18-112 (N-terminal domain of alpha(2)-macroglobulin receptor associated protein), at 750 MHz.

Carbon Isotopes↗
PubMed2000

3hJ coupling between C(alpha) and H(N) across hydrogen bonds in proteins.

J couplings between (13)C(alpha) and (1)H(N) across hydrogen bonds in proteins are reported for the first time, and a two- or three-dimensional NMR technique for their measurement is presented. The technique exploits the TROSY effect, i.e., the degree of interference between dipolar and chemical shift anisotropy relaxation mechanisms, for sensitivity enhancement. The 2D or 3D spectra exhibit E.COSY patterns where the splittings in the (13)CO and (1)H(N) dimensions are (1)J((13)C(alpha), (13)CO) and the desired (3h)J((13)C(alpha), (1)H(N)), respectively. A demonstration of the new method is shown for the (15)N,(13)C-labeled protein chymotrypsin inhibitor 2 where 17 (3h)J((13)C(alpha), (1)H(N)) coupling constants ranging from 0 to 1.4 Hz where identified and all of positive sign.

Carbon↗
PubMed2000

Pericardiocentesis: differential aspects of a common procedure.

OBJECTIVE: To evaluate the risk and effectiveness of pericardiocentesis in primary and repeat cardiac tamponade. DESIGN: Retrospective analysis. SETTING: Intensive care unit in a medical university hospital. PATIENTS: Sixty-three consecutively admitted patients with cardiac tamponade. INTERVENTIONS: In all patients pericardiocentesis was performed via the subxiphoid pathway after echocardiographic detection of the pericardial effusion. MEASUREMENTS AND RESULTS: There was no adverse event in patients undergoing primary pericardiocentesis, which was sufficient to resolve pericardial effusion in 51 of 63 patients (81%). However, repeat pericardiocentesis necessitated by the recurrence of symptomatic pericardial effusion yielded suboptimal results in 10 of 12 patients (83%). CONCLUSION: Pericardiocentesis is the treatment of choice for primary symptomatic pericardial effusion. In recurrent pericardial effusion surgical approaches appear to be preferable.

Adult↗
PubMed2000

Bone morphogenetic protein 2 (BMP-2) induces sequential changes of Id gene expression in the breast cancer cell line MCF-7.

Bone morphogenetic proteins (BMPs) are involved in the development of various organs including the mammary gland. They are well-regulated and act in a time-, concentration- and cell-type-specific manner. We found that BMP-2 is expressed in primary breast tumor tissue samples and in breast cancer cell lines. Hybridization of labeled cDNA, obtained from the breast cancer cell line MCF-7, against the Atlas human cDNA expression array revealed differential gene expression depending on BMP-2 treatment. The most prominent changes were observed for the helix-loop-helix proteins Id-1, Id-2 and Id-3. Id-1 expression had increased severalfold after 4 h and was even higher after 24 h. Id-2 and Id-3 were more strongly induced after 4 h and showed no further significant change after 24 h. Analysis of cell-cycle distribution revealed a marked increase of the sub-G1 phase after 48 h in serum-deprived cells. In the presence of BMP-2 no change was observed over 48 h indicating that BMP-2 does not induce apoptosis. In addition, expression of caspase-3 was reduced in BMP-2-treated cells after 24 h. In summary, our results clearly indicate that BMP-2 is a susceptibility factor keeping the cells ready for the integration of various other signals for cell progression.

Bone Morphogenetic Protein 2↗
PubMed2000

The early response genes c-jun and HSP-70 are induced in regional cardiac stunning in conscious mammals.

OBJECTIVES: A reversible contractile dysfunction without necrosis after transient myocardial ischemia has been termed stunning. The molecular mechanisms underlying this phenomenon are only now beginning to be unraveled. It is conceivable that the expression of early-response genes may play a crucial role in stunning. METHODS: The expression of HSP-70, c-jun, and GRP-94 was investigated in a chronically instrumented dog model (n = 9). The left anterior descending coronary artery was occluded temporarily for 10 minutes after the animals had fully recovered from instrumentation. The wall thickening fraction was measured in the left anterior descending coronary artery and the nonischemic ramus circumflex of the left coronary artery-perfused region. When the wall thickening fraction of the left anterior descending coronary artery had recovered to 50% of preocclusion values, tissue samples were obtained from the areas perfused by the left anterior descending coronary artery and the nonischemic ramus circumflex of the left coronary artery. RESULTS: The messenger RNA of HSP-70 was increased to 214% +/- 26% in the area perfused by the left anterior descending artery compared with that perfused by the nonischemic ramus circumflex of the left coronary artery. There was no difference in the messenger RNA of GRP-94. The HSP-70 content was elevated to 130% +/- 14% in the left anterior descending artery compared with the area perfused by the ramus circumflex of the left coronary artery, and the c-jun protein content was 70% +/- 25% higher in the ischemic area compared with the control area. CONCLUSIONS: The induction of early-response genes observed here may indicate that they play an adaptive role in myocardial stunning, even in conscious mammals.

Animals↗
PubMed2000

Recovery from myocardial stunning is faster with desflurane compared with propofol in chronically instrumented dogs.

Volatile anesthetics exert a protective role in myocardial ischemia. An increase in sympathetic tone might exert deleterious effects on the ischemic myocardium. The use of the volatile anesthetic desflurane in myocardial ischemia is controversial because of its sympathetic activation. We compared propofol and desflurane on myocardial stunning in chronically instrumented dogs. Mongrel dogs (n = 8) were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure, rate of rise of left ventricular pressure, and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed the induction of reversible LAD-ischemia. Two experiments were performed in a cross-over fashion on separate days: 1) Induction of 10 min of LAD-ischemia during desflurane anesthesia and 2) Induction of 10 min of LAD-ischemia during propofol anesthesia. Both anesthetics were discontinued immediately after completion of ischemia. WTF was measured at predetermined time points until complete recovery from ischemic dysfunction occurred. Both anesthetics caused a significant decrease of WTF in the LAD-perfused myocardium. LAD-ischemia led to a further significant decrease of LAD-WTF in both groups. During the first 3 h of reperfusion, WTF was significantly larger in the desflurane group. Mean arterial pressure and heart rate were greater during ischemia and the first 10 min of reperfusion in the desflurane group compared with the propofol group. Recovery from myocardial stunning in dogs was faster when desflurane was used at the time of ischemia as compared with propofol anesthesia. The mechanism for this difference is unclear, but sympathetic activation by desflurane was not a limiting factor for ischemic tolerance in chronically instrumented dogs.

Anesthetics, Inhalation↗
PubMed2000

Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy: long term follow up of the first series of 25 patients.

OBJECTIVE: To determine the long term outcome in patients treated with percutaneous transluminal septal myocardial ablation (PTSMA) for hypertrophic obstructive cardiomyopathy (HOCM). DESIGN AND SETTING: Observational, single centre study. PATIENTS: 25 patients (13 women, 12 men, mean (SD) age 54.7 (15.0) years) with drug treatment resistant New York Heart Association (NYHA) class 2.8 (0. 6) symptoms attributed to a high left ventricular outflow gradient (LVOTG) and a coronary artery anatomy suitable for intervention. INTERVENTION: PTSMA by injection of 4.1 (2.6) ml of alcohol (96%) into 1.4 (0.6) septal perforator arteries to ablate the hypertrophied interventricular septum. OUTCOME MEASURES: During in-hospital follow up, enzyme rise, the frequency of atrioventricular conduction lesions requiring permanent DDD pacing, and in-hospital mortality were assessed. Long term follow up (30 (4) months, range 24-36 months) included symptoms, echocardiographic measurements of left atrial and left ventricular dimensions and function, and LVOTG. RESULTS: Mean postinterventional creatine kinase rise was 780 (436) U/l. During PTSMA 13 patents developed total heart block, permanent pacing being necessary in five of them. One 86 year old patient died from ventricular fibrillation associated with intensive treatment (beta mimetic and theophylline) for coexistent severe obstructive airway disease. After three months, three patients underwent re-PTSMA because of a dissatisfactory primary result, leading to LVOTG elimination in all of them. During long term follow up, LVOTG showed sustained reduction (3 (6) mm Hg at rest and 12 (19) mm Hg with provocation) associated with stable symptomatic improvement (NYHA class 1.2 (1.0)) and without significant global left ventricular dilatation. CONCLUSIONS: PTSMA is an effective non-surgical technique for reduction of symptoms and LVOTG in HOCM. Prospective, long term observations of larger populations are necessary in order to determine the definitive significance of the procedure.

Angioplasty, Balloon, Coronary↗
PubMed2000

Biochemical mechanism(s) of stunning in conscious dogs.

The mechanism(s) underlying contractile dysfunction in cardiac stunning is not completely understood. The expression and/or the phosphorylation state of cardiac Ca(2+) homoeostasis-regulating proteins might be altered in stunning. We tested this hypothesis in a well-characterized model of stunning. Conscious dogs were chronically instrumented, and the left anterior descending artery (LAD) was occluded for 10 min. Thereafter, reperfusion of the LAD was initiated. Tissues from reperfused LAD (stunned) and Ramus circumflexus (control) areas were obtained when left ventricular regional wall thickening fraction had recovered by 50%. Northern and Western blotting revealed no differences in the expression of the following genes: phospholamban, calsequestrin, sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, and the inhibitory subunit of troponin I (TnI). However, the phosphorylation state of TnI and phospholamban were reduced in the LAD area. Fittingly, cAMP levels were reduced by 28% (P < 0.05). It is concluded that the contractile dysfunction in cardiac stunning might be mediated in part by decreased levels of cAMP and subsequently a reduced phosphorylation state of phospholamban and TnI.

Animals↗
PubMed1999

Expression of cardiac calcium regulatory proteins in atrium v ventricle in different species.

The duration of contraction in isolated electrically driven preparations from atrium and ventricle of mouse, rat, rabbit, guinea-pig and dog was consistently shorter in atrial compared to ventricular preparations. Overexpression of phospholamban (PLB) in transgenic mice prolonged duration of contraction, underscoring the importance of PLB for kinetics of cardiac contractility. The expression of regulatory proteins was studied by Western and Northern blot analysis. In rat myocardium, expression of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) was higher in atrium than in ventricle, as was also observed in the rabbit, guinea-pig and wild-type mouse samples. Canine myocardium, however, had similar levels of SERCA (protein and mRNA) in atrium and ventricle. PLB and calsequestrin on protein and RNA levels were lower in atrium than in ventricle from rat, rabbit, guinea-pig and wild-type mouse. PLB protein and RNA levels were higher in ventricle than in atrium at ages 1 and 5 days postnatally and in adult rats. SERCA protein and RNA levels were higher in ventricle than in atrium at days 1 and 5 after birth, but lower in ventricle than in atrium in adult rats. In dog, the calsequestrin level was identical in atrium and ventricle (protein and mRNA) and PLB did not differ between atrium vs ventricle at the protein level but was lower at the mRNA level. Also, Ca2+ uptake was higher in atrium than in ventricle in the dog samples. The expression of the inhibitory subunit of troponin was unchanged between atrium and ventricle in all species studied (protein and mRNA). In dog, protein expression of triadin and junctin was lower in atrium vs ventricle. Triadin mRNA was not altered in dog atrium vs ventricle. In summary, while the hastened relaxation of atrium vs ventricle correlates in part with the lower expression of PLB and higher expression of SERCA, altered regional expression of other SR proteins handling Ca2+ may also play an important role in some species.

Animals↗
PubMed1999

13C natural abundance S3E and S3CT experiments for measurement of J coupling constants between 13Calpha or 1Halpha and other protons in a protein.

It is demonstrated that the spin-state-selective pulse sequence elements, S3E and S3CT, previously introduced for measurement of J coupling constants in 15N-labeled proteins can be applied for work with peptides and proteins with 13C at the natural abundance level. In addition, a method is described for suppression of crosstalk caused by passive spin flips and pulse imperfections, which otherwise results in systematically underestimated J coupling constants and thereby inaccurate structural constraints. This method is also applicable for crosstalk suppression in applications of S3E and S3CT to 13C- or 15N-labeled samples. Experimental confirmation is obtained using a 10 mM BPTI sample focusing on 13C in the alpha position. The measured J coupling constants include 3J(HN-Halpha) and 3J(Halpha-Hbeta) related to the phi and chi1 angles, respectively.

Carbon Isotopes↗
PubMed1999

Spin-state-selective TPPI: a new method for suppression of heteronuclear coupling constants in multidimensional NMR experiments.

A novel multidimensional NMR pulse sequence tool, spin-state-selective time-proportional phase incrementation (S(3) TPPI), is introduced. It amounts to application of different TPPIs on the two components of doublets so that their frequencies can be manipulated independently. The chief application is for suppression of large heteronuclear one-bond coupling constants in indirect dimensions of multidimensional experiments without interchanging the two transverse magnetization components of doublets as conventional decoupling does, which is advantageous when they relax at different rates such as by partial compensation of dipolar and CSA relaxation contributions. For experimental confirmation we use a sample of (15)N-labeled neural cell adhesion molecule modules 1 and 2, a protein with a molecular weight of about 20 kDa. The new tool is general and can be combined with many multidimensional NMR experiments for proteins.

Magnetic Resonance Spectroscopy↗
PubMed1999

The role of coherence transfer efficiency in design of TROSY-type multidimensional NMR experiments.

An improved method for TROSY-type (Pervushin et al., Proc. Natl. Acad. Sci. USA 94, 12366-12371 (1997)) heteronuclear two-dimensional correlation involving protons of negligible CSA is presented. Rather than applying a simple INEPT sequence for back-transfer to protons (Pervushin et al., J. Am. Chem. Soc. 120, 6394-6400 (1998)), we replace the pi/2 proton pulse in INEPT by a spin-state-selective coherence transfer element (Sorensen et al., J. Biomol. NMR 10, 181-186 (1997)) and maintain broadband decoupling during acquisition. Theoretically that results in a sensitivity enhancement of a factor of 2. The new method is demonstrated using a (13)C,(15)N-labeled protein sample, RAP 18-112 (N-terminal domain of alpha(2)-macroglobulin receptor associated protein), at 750 MHz.

Magnetic Resonance Spectroscopy↗
PubMed1999

Optimization of three-dimensional TROSY-type HCCH NMR correlation of aromatic (1)H-(13)C groups in proteins.

Improved methods for three-dimensional TROSY-Type HCCH correlation involving protons of negligible CSA are presented. The TROSY approach differs from the conventional approach of heteronuclear decoupling in evolution and detection periods by not mixing fast and slowly relaxing coherences and usually suppressing the former. Pervushin et al. (J. Am. Chem. Soc. 120, 6394-6400 (1998)) have proposed a 3D TROSY-type HCCH experiment where the TROSY approach is applied only in one of the (13)C dimensions. A new pulse sequence applying the TROSY approach in both indirect dimensions is advantageous when the TROSY effect of the carbons is large or when a relatively high resolution is required. For lower resolutions or moderate TROSY effects we show that it is possible to combine the best of both worlds, namely to suppress heteronuclear couplings without mixing fast and slowly relaxing coherences while at the same time superimpose the two components and thus have both contribute to the detected signal. That is possible using the novel technique of Spin-State-Selective Time-Proportional Phase Incrementation (S(3) TPPI). The new 3D S(3) TPPI TROSY HCCH method is demonstrated on a (13)C,(15)N-labeled protein sample, RAP 18-112 (N-terminal domain of alpha(2)-macroglobulin receptor associated protein), at 750 MHz and average sensitivity enhancements of 10% are obtained for the cross peaks in comparison to methods based on conventional decoupling on one of the carbons or on TROSY on both carbons.

Magnetic Resonance Spectroscopy↗