Pre-procedural high-pitch coronary CT angiography assessment of patients undergoing transcatheter aortic valve implantation (TAVI) without patient-specific adjustment: analysis of diagnostic performance.

AIM: To evaluate the ability to assess the coronary arteries using pre-procedural computed tomography (CT; high-pitch mode) in patients referred for transcatheter aortic valve implantation (TAVI). METHODS AND MATERIALS: CT and invasive coronary angiography (ICA) were performed pre-TAVI in 100 patients (46 women; 79 ± 5.9 years). CT was performed in prospectively ECG-triggered high-pitch mode after intravenous administration of 70 ml iodinated contrast medium. Image quality was assessed using a four-point scale (graded 0-3). Significant coronary artery stenosis (≥50% diameter) was graded as either present or absent by one observer and in one-third of patients by two observers independently. ICA was the standard of reference. Results were reported per segment and per patient. RESULTS: Twenty-two percent of patients had known coronary artery disease (CAD). In two cases, a coronary anomaly was detected. Diagnostic image quality (grade 1-3) was achieved in 30.3% of segments. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75%, 80.5%, 16%, and 98.5%, respectively. Significant coronary stenosis could be ruled out completely in all segments in three patients. The interrater agreement per patient was excellent (kappa = 1). CONCLUSION: Relevant coronary findings can frequently be observed in high-pitch TAVI-planning CT. Despite the limitations of the technique and in patients referred to pre-TAVI evaluation (rapid heart rate, coronary calcifications, etc.), a valid evaluation of coronary arteries is possible in a considerable proportion of segments with a high NPV; however, few studies were completely free of motion artefacts to dependably exclude CAD using this technique in this challenging group of patients.

High inter- and intra-observer agreement in mapping sequences compared to classical Lake Louise Criteria assessment of myocarditis by inexperienced observers.

AIM: To investigate the observer agreement for the assessment of chronic myocarditis by native T1 and T2 relaxation times, post-contrast T1 relaxation time, and extracellular volume (ECV) fraction, compared to Lake Louise Criteria: oedema ratio (OR) and early gadolinium enhancement ratio (EGEr). MATERIALS AND METHODS: Data were collected retrospectively on 71 consecutive patients who underwent cardiac magnetic resonance imaging as part of a complete diagnostic work-up according to current guidelines for suspected myocarditis. Thirteen cases were excluded due to previous myocardial infarction or technical issues. To test for intra- and interobserver agreement, the determination of the myocardial native T1 and T2 relaxation times, post-contrast T1 relaxation time, ECV, OR and EGEr was undertaken by two medical school graduates after comprehensive training. Bland-Altman analysis and intraclass correlation coefficient (ICC) were assessed. RESULTS: The final analysis included 27 patients with chronic myocarditis, 21 patients with dilated cardiomyopathy and/or hypertensive heart disease, and 10 patients with unremarkable investigations in the control group. Excellent interobserver agreement was obtained for native T1 and T2 relaxation times, post-contrast T1 relaxation time and ECV, with ICC of 0.982/0.977/0.991/0.994, p < 0.001. Interobserver agreement was lower for OR and EGEr, with ICC of 0.841 and 0.818, p < 0.001, respectively. Mapping parameters (cut-off values: T1 1,070 ms, T2 54 ms, ECV 30%) yield good performance in the diagnosis of chronic myocarditis with the best sensitivity/specificity/accuracy of 93%/80%/88% for ECV, followed by 70%/80%/74% for T2, and 52%/88%/69% for T1. CONCLUSIONS: mapping parameters show excellent agreement between observers in the assessment of myocarditis.

Comparison of volumetric and functional parameters in simultaneous cardiac PET/MR: feasibility of volumetric assessment with residual activity from prior PET/CT.

OBJECTIVE: To compare cardiac left ventricular (LV) parameters in simultaneously acquired hybrid fluorine-18-fluorodeoxyglucose ([18F] FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with residual tracer activity of upstream PET/CT. METHODS: Twenty-nine patients (23 men, age 58±17 years) underwent cardiac PET/MRI either directly after a non-cardiac PET/CT with homogenous cardiac [18F] FDG uptake (n=20) or for viability assessment (n=9). Gated cardiac [18F] FDG PET and cine MR sequences were acquired simultaneously and evaluated blinded to the cross-imaging results. Image quality (IQ), end-diastolic (LVEDV), end-systolic volume (LVESV), ejection fraction (LVEF) and myocardial mass (LVMM) were measured. Pearson correlation and intraclass correlation coefficient (ICC), regression and a Bland-Altman analysis were assessed. RESULTS: Except LVMM, volumetric and functional LV parameters demonstrated high correlations (LVESV: r=0.97, LVEDV: r=0.95, LVEF: r=0.91, LVMM: r=0.87, each p<0.05), but wide limits of agreement (LOA) for LVEDV (-25.3-82.5ml); LVESV (-33.1-72.7ml); LVEF (-18.9-14.8%) and LVMM (-78.2-43.2g). Intra- and interobserver reliability were very high (ICC≥0.95) for all parameters, except for MR-LVEF (ICC=0.87). PET-IQ (0-3) was high (mean: 2.2±0.9) with significant influence on LVMM calculations only. CONCLUSION: In simultaneously acquired cardiac PET/MRI data, LVEDV, LVESV and LVEF show good agreement. However, the agreement seems to be limited if cardiac PET/MRI follows PET/CT and only the residual activity is used. KEY POINTS: • [ 18 F] FDG PET-MRI is feasible with residual [ 18 F] FDG activity in patients with homogenous cardiac uptake. • Cardiac volumes and function assessed by PET/MRI show good agreement. • LVEDV and LVESV are underestimated; PET overestimates LVMM and LVEF. • Cardiac PET and MRI data correlate better when acquired simultaneously than sequentially. • PET and MRI should not assess LV parameters interchangeably.

Modern Imaging of Myocarditis: Possibilities and Challenges / Moderne Bildgebung bei Myokarditis: Möglichkeiten und Herausforderungen

UNLABELLED: Myocarditis is known as the chameleon of cardiac diseases. The symptoms and the course of disease vary greatly so that it is often challenging to establish a diagnosis. Early and accurate diagnosis is of utmost importance, since myocarditis is one of the leading causes of sudden cardiac death in young adults and represents an important precursor to dilated cardiomyopathy. Due to the constraints of the routinely used diagnostic approach, including clinical history and examination, laboratory testing, and electrocardiogram, different imaging modalities have emerged over the last decades as contributors to the noninvasive diagnosis of myocarditis. With this interdisciplinary review we would like to present the current state-of-the-art imaging of myocarditis across all available imaging modalities (i. e., echocardiography, cardiac magnetic resonance, cardiac computed tomography, and nuclear medicine). Furthermore, we present novel imaging techniques that might become useful in the near future for easier and more accurate diagnosis of this highly relevant disease. KEY POINTS: • Different imaging modalities are increasingly used in the diagnostic workup of myocarditis. • Several emerging imaging techniques are currently on the way to becoming part of the clinical routine. • This review summarizes the diagnostic value of echocardiography, CMR, CT, and nuclear medicine imaging. • There is special focus on the possibilities and challenges of novel imaging tools within the different modalities.

Effective diameter of the aortic annulus prior to transcatheter aortic valve implantation: influence of area-based versus perimeter-based calculation.

In computed tomography (CT) evaluation prior to transcatheter aortic valve implantation area- and perimeter-based calculation of the aortic annulus diameter, the so-called effective annulus diameter (ED), is the preferred parameter for decision making regarding prosthesis sizes. Currently, it is unclear how relevant the differences between the two methods of measurement are and how they are influenced by the cardiac cycle. The aim of this study was to compare area- and perimeter-based measurements in computed tomography derived aortic annulus sizing. A total of 60 patients who underwent evaluation for transcatheter aortic valve implantation were included in this study. All patients received pre-procedural ECG gated CT. The aortic annulus area and perimeter were measured and the derived ED compared using parametric statistics and Bland and Altman analysis. The mean patient age was 80.2 ± 4 years. Systolic aortic annulus area and perimeter were higher compared to diastolic results (mean difference area 12.8 ± 24 mm(2) and perimeter 0.72 ± 1 mm; p = 0.009-0.068). Both the area- and perimeter-based ED had a good agreement within two standard deviations for systolic and diastolic measurements. Effective diameter measurements derived from the area were significantly smaller compared to perimeter-based measurements (mean difference: systolic 0.72 ± 0.3 mm and diastolic 0.81 ± 0.4 mm; p < 0.001). While the area-based ED was significantly influenced by the cardiac cycle with a mean difference of 0.4 ± 0.6 mm (p = 0.009), no significant difference was found for the perimeter-based ED (mean difference: 0.2 ± 0.4; p = 0.07). For patients undergoing CT evaluation prior to transcatheter aortic valve implantation, the perimeter-based effective annulus diameter provides a reliable parameter for annulus sizing without significant affection by the cardiac cycle and therefore facilitates annulus measurements with a single heart phase. However, perimeter-based diameters of the annulus are significantly larger than area-based diameters.

Post-processing in cardiovascular computed tomography: performance of a client server solution versus a stand-alone solution.

PURPOSE: To compare the performance of server-based (CSS) versus stand-alone post-processing software (ES) for the evaluation of cardiovascular CT examinations (cvCT) and to determine the crucial steps. MATERIALS AND METHODS: Data of 40 patients (20 patients for coronary artery evaluation and 20 patients prior to transcatheter aortic valve implantation [TAVI]) were evaluated by 5 radiologists with CSS and ES. Data acquisition was performed using a dual-source 128-row CT unit (SOMATOM Definition Flash, Siemens, Erlangen, Germany) and a 64-row CT unit (Brilliance 64, Philips, Hamburg, Germany). The following workflow was evaluated: Data loading, aorta and coronary segmentation, curved multiplanar reconstruction (cMPR) and 3 D volume rendering technique (3D-VRT), measuring of coronary artery stenosis and planimetry of the aortic annulus. The time requirement and subjective quality for the workflow were evaluated. RESULTS: The coronary arteries as well as the TAVI data could be evaluated significantly faster with CSS (5.5  ±  2.9  min and 8.2  ±  4.0  min, respectively) than with ES (13.9  ±  5.2  min and 15.2  ±â€Š 10.9  min, respectively, p ≤  0.01). Segmentation of the aorta (CSS: 1.9 ±  2.0  min, ES: 3.7  ±  3.3  min), generating cMPR of coronaries (CSS: 0.5  ±  0.2  min, ES: 5.1  ±  2.6  min), aorta and iliac vessels (CSS: 0.5  ±  0.4  min and 0.4  ±  0.4  min, respectively, ES: 1.6  ±  0.7  min and 2.8  ±  3  min, respectively) could be performed significantly faster with CSS than with ES with higher quality of cMPR, measuring of coronary stenosis and 3D-VRT (p < 0.05). CONCLUSION: Evaluation of cvCT can be accomplished significantly faster and better with CSS than with ES.  The segmentation remains the most time-consuming workflow step, so optimization of segmentation algorithms could improve performance even further.

[Imaging prior to transcatheter aortic valve implantation]. / Bildgebung vor Transkatheteraortenklappenersatz.

Percutaneous transcatheter aortic valve implantation (TAVI) is an established alternative to open heart surgery in patients with severe aortic stenosis (AS) unsuitable for conventional aortic valve replacement due to comorbidities with a high perioperative risk or contraindications. Preprocedural imaging plays a major role for adequate determination of indications and prosthesis selection, prosthesis sizing and therefore for a reduction of periprocedural complications. Besides Doppler echocardiography which is mainly used for grading of the severity of aortic valve stenosis and peri-interventional imaging, cardiac computed tomography (CCT) is the imaging modality of choice. The CCT procedure not only allows for reliably assessment and measuring of the complex 3-dimensional geometry of the aortic root but also for the aorta and the peripheral vessels used as potential access paths.

Role of preprocedural computed tomography in transcatheter aortic valve implantation.

UNLABELLED: Transcatheter aortic valve implantation (TAVI) is currently considered an acceptable alternative for the treatment of patients with severe aortic stenosis and a high perioperative risk or a contraindication for open surgery. The benefit of TAVI significantly outweighs the risk of the procedure in patients requiring treatment that are not suitable for open surgery, and leads to a lower mortality in the one-year follow-up. The absence of a direct view of the aortic root and valve remains a challenge for the transcatheter approach. While direct inspection of the aortic valve during open surgery allows an adequate prosthesis choice, it is crucial for TAVI to know the individual anatomical details prior to the procedure in order to assure adequate planning of the procedure and proper prosthesis choice and patient selection. Among the imaging modalities available for the evaluation of patients prior to TAVI, computed tomography (CT) plays a central role in patient selection. CT reliably visualizes the dimensions of the aortic root and allows a proper choice of the prosthesis size. The morphology of the access path and relevant comorbidities can be assessed. The present review summarizes the current state of knowledge regarding the value of CT in the evaluation of patients prior to TAVI. KEY POINTS: CT plays a central role in patient selection and planning prior to TAVI. ▶ CT reliably detects the dimensions of the aortic root including the size of the aortic annulus, the degree of valve calcification and the morphology of the access routes. ▶ CT provides a more accurate measurement of the aortic annulus than 2D TEE and CT is the only imaging modality that allows a risk assessment for paravalvular leakages based on the calcification of the aortic valve.

[MRI for myocarditis]. / MRT bei Myokarditis.

Cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for the non-invasive assessment in patients with suspected myocarditis, especially after exclusion of acute coronary syndrome (ACS) for the differential diagnosis. Various MRI parameters are available which have different accuracies. Volumetric and functional ventricular assessment and the occurrence of pericardial effusion alone demonstrate only a poor sensitivity and specificity. The calculation of the T2-ratio (edema assessment), the early or global relative myocardial enhancement (gRE) and the late gadolinium enhancement (LGE), which represents irreversibly injured myocardium, are more specific parameters. All MRI parameters demonstrate the best accuracy in infarct-like acute myocarditis, whereas in chronic myocarditis sensitivity and specificity are less accurate. Therefore, a multisequential (at least two out of three parameters are positive) approach is recommended. The assessment of the value of newer, more quantitative MRI sequences, such as T1 and T2-mapping is still under investigation.

Role of preprocedural computed tomography in transcatheter aortic valve implantation.

UNLABELLED: Transcatheter aortic valve implantation (TAVI) is currently considered an acceptable alternative for the treatment of patients with severe aortic stenosis and a high perioperative risk or a contraindication for open surgery. The benefit of TAVI significantly outweighs the risk of the procedure in patients requiring treatment that are not suitable for open surgery, and leads to a lower mortality in the one-year follow-up. The absence of a direct view of the aortic root and valve remains a challenge for the transcatheter approach. While direct inspection of the aortic valve during open surgery allows an adequate prosthesis choice, it is crucial for TAVI to know the individual anatomical details prior to the procedure in order to assure adequate planning of the procedure and proper prosthesis choice and patient selection. Among the imaging modalities available for the evaluation of patients prior to TAVI, computed tomography (CT) plays a central role in patient selection. CT reliably visualizes the dimensions of the aortic root and allows a proper choice of the prosthesis size. The morphology of the access path and relevant comorbidities can be assessed. The present review summarizes the current state of knowledge regarding the value of CT in the evaluation of patients prior to TAVI. CT plays a central role in patient selection and planning prior to TAVI. CT reliably detects the dimensions of the aortic root including the size of the aortic annulus, the degree of valve calcification and the morphology of the access routes. KEY POINTS: CT plays a central role in patient selection and planning prior to TAVI. CT reliably detects the dimensions of the aortic root including the size of the aortic annulus, the degree of valve calcification and the morphology of the access routes. CT provides a more accurate measurement of the aortic annulus than 2D TEE and CT is the only imaging modality that allows a risk assessment for paravalvular leakages based on the calcification of the aortic valve.

[Memento mori: what can be learned from early paintings and woodcuts about death and dying in former times?]. / Memento mori: Was lehren die alten Abbildungen über das Sterben in früheren Zeiten?

What was the impression on death and dying from people living in the 15th century? To answer this question written information is rare on this topic, as few people were able to read at that time, but paintings and early woodcuts may be helpful. Danses macabres (Totentänze) could be seen in Tallinn (formerly Reval), Lübeck, Bern and other places: parts of the original dance macabre still exist in Tallinn, but those in Bern and Lübeck are destroyed; copies however may give a decent impression of their former appearance. At all these dances macabre the death invites persons for a dance: the pope, the Kaiser, the king, the queen, various noblemen and citizens, even young women and small children; to dance with the death meant to die. The death does not dance with any old person. At the time of these dances macabre epidemics and famines were frequent causes of untimely early death.--A booklet Ars moriendi was published about 1470 and taught people how to behave at their hour of death; various devils appear at the deathbed haggling for the soul of the dying person. Thereafter an angel convinces him to trust in god and to resist those false promises of the devil.Nowadays dying is quite different. Usually persons die at very old age and are frequently demented, they die in hospitals, even in intensive care units and possibly without attendance of family members. They may have suffered for a long time and have spent years in nursing homes. Today dying may be just a release from very long suffering.

Insights into immunophilin structure and function.

The immunophilins are proteins which are capable of influencing the immune response in combination with an immunosuppressive drug. Their natural function, however, is mainly the cis/trans isomerization of peptidyl-prolyl bonds in other proteins. This review lists all immunophilin structure coordinates currently available in the RCSB protein data bank and highlights the key active-site factors that define their catalytic and immunological action. In addition, an overview of biologically-relevant functions is provided for various immunophilin members.

Mesenchymal stem cells improve murine acute coxsackievirus B3-induced myocarditis.

AIMS: Coxsackievirus B3 (CVB3)-induced myocarditis, initially considered a sole immune-mediated disease, also results from a direct CVB3-mediated injury of the cardiomyocytes. Mesenchymal stem cells (MSCs) have, besides immunomodulatory, also anti-apoptotic features. In view of clinical translation, we first analysed whether MSCs can be infected by CVB3. Next, we explored whether and how MSCs could reduce the direct CVB3-mediated cardiomyocyte injury and viral progeny release, in vitro, in the absence of immune cells. Finally, we investigated whether MSC application could improve murine acute CVB3-induced myocarditis. METHODS AND RESULTS: Phase contrast pictures and MTS viability assay demonstrated that MSCs did not suffer from CVB3 infection 4-12-24-48 h after CVB3 infection. Coxsackievirus B3 RNA copy number decreased in this time frame, suggesting that no CVB3 replication took place. Co-culture of MSCs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis, oxidative stress, intracellular viral particle production, and viral progeny release in a nitric oxide (NO)-dependent manner. Moreover, MSCs required priming via interferon-γ (IFN-γ) to exert their protective effects. In vivo, MSC application improved the contractility and relaxation parameters in CVB3-induced myocarditis, which was paralleled with a reduction in cardiac apoptosis, cardiomyocyte damage, left ventricular tumour necrosis factor-α mRNA expression, and cardiac mononuclear cell activation. Mesenchymal stem cells reduced the CVB3-induced CD4- and CD8- T cell activation in an NO-dependent way and required IFN-γ priming. CONCLUSION: We conclude that MSCs improve murine acute CVB3-induced myocarditis via their anti-apoptotic and immunomodulatory properties, which occur in an NO-dependent manner and require priming via IFN-γ.

[Cases from the area between geriatrics and trauma surgery. Examples from the medical arbitration board]. / Fälle aus dem Grenzgebiet zwischen Geriatrie und Unfallchirurgie. Aus der Arbeit der Schlichtungsstelle.

Medical arbitration boards ("Schlichtungsstellen", expert panels for extrajudicial malpractice claim resolution) try to settle claims of suspected malpractice between patients and their physicians and to avoid court trials. Numerous studies found an increasing incidence of adverse events with rising age. Injuries that occur in the hospital are frequently beyond the specialty of the treating physician. Therefore, the physician has to broaden his diagnostic view beyond the borders of his own specialty to recognize injuries in his patients and to prevent malpractice claims.In this paper, we report on adverse events in elderly patients where the geriatrician/internist was accused of negligence for not having promptly recognized a fracture after a fall or having chosen an inadequate operative procedure. For example, the importance of weight bearing osteosynthesis, mandatory in hip fractures in the elderly population to prevent long-term immobilization, is discussed.Adverse events due to negligence are more frequent among the elderly; the reasons are discussed. They will never be entirely preventable. The data presented in this report may be helpful to recognize fractures in time and to ensure adequate treatment, in order to reduce the number of court claims.

[Diagnosis and treatment of femural neck fractures from the beginning to operative treatment: a historical overview]. / Zur Geschichte von Diagnostik und Therapie hüftnaher Femurfrakturen bis zum Beginn der operativen Therapie : Ein historischer Uberblick.

Operative stabilisation of femural neck fractures is a routine procedure nowadays and is usually performed without delay. Treatment by osteosynthesis or endoprosthesis allows immediate mobilisation with at least partial weight bearing.Immobilisation for months, associated with high mortality as practiced in former times, is nearly forgotten. We present a review on 430 years of diagnosis and treatment of these fractures since the first description by Ambroise Paré. In fact, it took 150 years to recognise the different locations of various hip fractures; at the time, fractures close to the caput were felt to have no chance of healing. Impacted fractures of the femural neck were first described 250 years after the first publication by A. Paré.This article also presents an overview on the development of various treatments to stabilise hip fractures: closed reduction and repositioning by internal rotation of the external rotated leg, positioning of the leg on the double inclined splint, different types of extension treatment and finally early operative procedures, when asepsis was established and fractures could be imaged by x-rays.

[Effectiveness and efficiency of stationary geriatric treatment of old and very old patients]. / Zur Effektivität und Effizienz der stationären geriatrischen Behandlung bei hochbetagten Patienten.

In this study we compared characteristics and treatment results in patients of 60 to 79 (group I, n = 682) and of 80 to 100 years of age (group II, n = 593) treated in a geriatric hospital. Neurologic diseases (mainly stroke) predominated in group I (38%), and patients with fractures in group II (53%). Diabetes mellitus and hyperlipidemia were less frequent in patients of group II, but overt cardial insufficiency was more frequent than in group I. While the effectiveness of geriatric treatment was identical in both groups, the efficiency-defined as progress per day-was in some parts slightly higher in group II. There are three independent variables strongly related to the decision of transfer into a nursing home: 1) Barthel Index on discharge; 2) Household-Size (living alone/living not allone); 3) Age.

Local vascular complications after use of the hemostatic puncture closure device Angio-Seal.

BACKGROUND: As an alternative to manual pressure techniques new systems for achieving arterial hemostasis after cardiac catheterization were developed. Here we report about the diagnosis and therapy of femoral artery complications after use of the closure device Angio-Seal, consisting of an intraarterial anchor and extravascular collagen plug. PATIENTS AND METHODS: Angio-Seal was deployed in 350 patients undergoing cardiac catheterization. Vascular investigations after device application consisted of ankle/brachial-pressure-index measurement, duplex sonography, and angiography. RESULTS: Vascular complications occurred in 10 of 350 patients. In two patients complete occlusions of the superficial femoral artery required immediate vascular surgery. Stenoses of the superficial (five patients) and the common (three patients) femoral arteries were diagnosed in 8 cases. Of these 10 patients eight were obese, in 2 cases there was a further catheterization with Angio-Seal device application via the same femoral approach. Until now six patients underwent successful surgery: in 4 cases the whole Angio-Seal device was located intraarterially, there was 1 case of intima-dissection, and 1 case remained unclear due to a diagnostic delay of 7 months. In three patients with stenoses of the common femoral arteries without hemodynamic relevance no therapy was required. CONCLUSIONS: Occlusions or stenoses of femoral arteries after use of Angio-Seal can be diagnosed easily by duplex sonography. All hemodynamic relevant complications (n = 7 of 350 [2%]) concerned a puncture of superficial femoral arteries. In these patients vascular surgery seems to be an adequate therapy.

Solution structure and dynamics of the functional domain of Paracoccus denitrificans cytochrome c(552) in both redox states.

A soluble and fully functional 10.5 kDa fragment of the 18.2 kDa membrane-bound cytochrome c(552) from Paracoccus denitrificans has been heterologously expressed and (13)C/(15)N-labeled to study the structural features of this protein in both redox states. Well-resolved solution structures of both the reduced and oxidized states have been determined using high-resolution heteronuclear NMR. The overall protein topology consists of two long terminal helices and three shorter helices surrounding the heme moiety. No significant redox-induced structural differences have been observed. (15)N relaxation rates and heteronuclear NOE values were determined at 500 and 600 MHz. Several residues located around the heme moiety display increased backbone mobility in both oxidation states, while helices I, III, and V as well as the two concatenated beta-turns between Leu30 and Arg36 apparently form a less flexible domain within the protein structure. Major redox-state-dependent differences of the internal backbone mobility on the picosecond-nanosecond time scale were not evident. Hydrogen exchange experiments demonstrated that the slow-exchanging amide proton resonances mainly belong to the helices and beta-turns, corresponding to the regions with high order parameters in the dynamics data. Despite this correlation, the backbone amide protons of the oxidized cytochrome c(552) exchange considerably faster with the solvent compared to the reduced protein. Using both differential scanning calorimetry as well as temperature-dependent NMR spectroscopy, a significant difference in the thermostabilities of the two redox states has been observed, with transition temperatures of 349.9 K (76.8 degrees C) for reduced and 307.5 K (34.4 degrees C) for oxidized cytochrome c(552). These results suggest a clearly distinct backbone stability between the two oxidation states.