Reorientational dynamics of highly asymmetric binary non-polymeric mixtures - a dielectric spectroscopy study.

We present an analysis of dielectric spectra measured for a specially designed non-polymeric asymmetric binary glass former characterized by a large difference of the component's Tg (ΔTg = 216 K). We cover the whole additive concentration range from 4% up to 90% (by mass). Two main relaxations α1 and α2 are identified, which are characterized by well separated time scales and are attributed to the dynamics associated with the high-Tg component (α1) and the low-Tg component (α2). Frequency-temperature superposition does not apply. To cope with the extraordinary spectral broadening, we introduce a model consisting of a generalized Cole-Davidson (α1) and a Havriliak-Negami function with a low frequency truncation (α2). Whereas the α1-relaxation reflects essentially homogeneous dynamics and its spectra mainly broaden on the high-frequency flank of the relaxation peak, the α2-relaxation becomes broader on the low-frequency side reflecting pronounced dynamic heterogeneity in a more or less arrested matrix of high-Tg molecules. From the extracted time constants, two glass transition temperatures Tg1 and Tg2 can be derived, showing a non-trivial concentration dependence for Tg2. Supplementary, we find a ß-relaxation. The total relaxation strength Δε strongly deviates from ideal mixing, and therefore care has to be taken interpreting the corresponding Δεαi as representation of molecular populations.

Reorientational dynamics in highly asymmetric binary low-molecular mixtures-A quantitative comparison of dielectric and NMR spectroscopy results.

Previously, we scrutinized the dielectric spectra of a binary glass former made by a low-molecular high-Tg component 2-(m-tertbutylphenyl)-2'-tertbutyl-9,9'-spirobi[9H]fluorene (m-TPTS; Tg = 350 K) and low-Tg tripropyl phosphate (TPP; Tg = 134 K) [Körber et al., Phys. Chem. Chem. Phys. 23, 7200 (2021)]. Here, we analyze nuclear magnetic resonance (NMR) spectra and stimulated echo decays of deuterated m-TPTS-d4 (2H) and TPP (31P) and attempt to understand the dielectric spectra in terms of component specific dynamics. The high-Tg component (α1) shows relaxation similar to that of neat systems, yet with some broadening upon mixing. This correlates with high-frequency broadening of the dielectric spectra. The low-Tg component (α2) exhibits highly stretched relaxations and strong dynamic heterogeneities indicated by "two-phase" spectra, reflecting varying fractions of fast and slow liquid-like reorienting molecules. Missing for the high-Tg component, such two-phase spectra are identified down to wTPP = 0.04, indicating that isotropic reorientation prevails in the rigid high-Tg matrix stretching from close to Tg TPP to Tg1 wTPP. This correlates with low-frequency broadening of the dielectric spectra. Two Tg values are defined: Tg1 (wTPP) displays a plasticizer effect, whereas Tg2 (wTPP) passes through a maximum, signaling extreme separation of the component dynamics at low wTPP. We suggest understanding the latter counter-intuitive feature by referring to a crossover from "single glass" to "double glass" scenario revealed by recent MD simulations. Analyses reveal that a second population of TPP molecules exists, which is associated with the dynamics of the high-Tg component. However, the fractions are lower than suggested by the dielectric spectra. We discuss this discrepancy considering the role of collective dynamics probed by dielectric but not by NMR spectroscopy.

Main and secondary relaxations of non-polymeric high-Tg glass formers as revealed by dielectric spectroscopy.

A series of high-Tg glass formers with Tg values varying between 347 and 390 K and molar masses in the range of 341 and 504 g mol-1 are investigated by dielectric spectroscopy. They are compared to paradigmatic reference systems. Differently polar side groups are attached to a rigid non-polar core unit at different positions. Thereby, the dielectric relaxation strength varies over more than two decades. All the relaxation features typical of molecular glass formers are rediscovered, i.e. stretching of the main (α-) relaxation, a more or less pronounced secondary (ß-) process, and a fragility index quite similar to that of other molecular systems. The position of the polar nitrile side group influences the manifestation of the ß-relaxation. The α-relaxation stretching displays the trend to become less with higher relaxation strength Δεα, confirming recent reports. Typical for a generic ß-process is the increase of its amplitude above Tg, which is found to follow a power-law behaviour as a function of the ratio τα/τß with a universal exponent; yet, its relative amplitude to that of the α-relaxation varies as does the temporal separation of both processes. The mean activation energy of the ß-process as well as the width of the energy distribution gß(E) increases more or less systematically with Tg. The latter is determined from the dielectric spectra subjected to a scaling procedure assuming a thermally activated process. Plotting gß(E) as a function of the reduced energy scale E/Tg, the distributions are centred between 19-35 and their widths differ by a factor 2-3.

Systematic differences in the relaxation stretching of polar molecular liquids probed by dielectric vs magnetic resonance and photon correlation spectroscopy.

Relaxation spectra of molecular glass formers devoid of secondary relaxation maxima, as measured by dielectric spectroscopy (DS), nuclear magnetic resonance (NMR) relaxometry, photon correlation spectroscopy (PCS), and Fabry-Perot interferometry, are quantitatively compared in terms of the Kohlrausch stretching parameter ßK. For a reliable estimate of ßK, the excess wing contribution has to be included in the spectral analysis. The relaxation stretching probed by PCS and NMR varies only weakly among the liquids (ßK = 0.58 ± 0.06). It is similar to that found in DS, provided that the liquid is sufficiently nonpolar (relaxation strength Δε≲6). For larger strengths, larger ßK DS (narrowed relaxation spectra) are found when compared to those reported from NMR and PCS. Frequency-temperature superposition (FTS) holds for PCS and NMR. This is demonstrated by data scaling and, for the few glass formers for which results are available, by the equivalence of the susceptibilities χPCS ″ωτ∝χNMR ″τ∝χNMR ″ω, i.e., measuring at a constant frequency is equivalent to measuring at a constant temperature or constant correlation time. In this context, a plot of the spin-lattice relaxation rate R1(T) as a function of the spin-spin relaxation rate R2(T) is suggested to reveal the stretching parameter without the need to perform frequency-dependent investigations. Dielectrically, we identify a trend of increasing deviations from FTS with increasing Δε. Depending on the technique and glass former, the relative relaxation strength of the excess wing varies, whereas its exponent appears to be method independent for a given substance. For polar liquids, we discuss possible reasons for the discrepancy between the results from PCS and NMR as compared to those from DS.

[Increased Ventricular Pacing Threshold Caused by Intake of Dronedaron]. / Erhöhung der ventrikulären Reizschwelle durch Dronedaron-Einnahme.

HISTORY: The 75 year old patient was hospitalized because of vertigo, exertional dyspnea and clamminess. Based on ischemic heart disease with sick sinus syndrome a pacemaker was implanted 5.5 years ago. In consequence of non-permanent atrial fibrillation Dronedaron was added to medication 8 months ago. FINDINGS AND DIAGNOSIS: The patient presented unstable. The ECG showed a second-degree atrioventricular block with wenckebach periodic and a frequency of 29 bpm. The pacemaker survey showed primary a proper atrial function but ineffective ventricular stimulation. THERAPY AND COURSE: After initial external pacing the pacemaker was reprogrammed and in this way the ventricle stimulated effectively. Dronedaron was ceased after checking trigger factors and the patient left hospital after 3 days free of complaints. The pacemaker survey 18 days later showed a proper function with stabilized pacing threshold close to the old level. CONCLUSIONS: In patients with dysfunction of a permanent pacemaker an increased pacing threshold should be excluded and if any the current medication needs to be controlled. Caution should be exercised to Dronedaron here.

Short-term growth hormone treatment and microcirculation: effects in patients with chronic kidney disease.

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and contributes significantly to the high long-term cardiovascular morbidity and mortality. The short-term cardiovascular effects of recombinant human growth hormone (rhGH) in CKD patients (stages III-V) and healthy controls (n=15 each) were explored in a single-center, non-randomized pilot study. Subjects were investigated before, after a 7 day treatment with rhGH, and after a 7 day wash-out period. Microcirculation was assessed by nailfold capillaroscopy and leg strain gauge plethysmography. Echocardiography was performed and serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) were determined. Before the start of rhGH therapy, mean post-ischemic maximum flow velocity of erythrocytes (V(RBC)) and leg blood flow (LBF) in CKD patients were significantly reduced to 68% and 75% of that seen in controls, whereas V(RBC) and LBF under resting conditions were comparable. Treatment with rhGH significantly increased V(RBC) and LBF under resting conditions. Whereas maximum post-ischemic V(RBC) was improved by rhGH in patients and controls, maximum post-ischemic LBF increased in controls only. This was paralleled by a non-significant reduction of total vascular resistance, and increased heart rate and cardiac index. In conclusion, CKD patients respond to short-term rhGH treatment with significantly improved capillary blood flow, whereas only minor effects on total peripheral resistance and cardiac output were noted.

Should we use the rate-adaptive AV delay in cardiac resynchronization therapy-pacing?

AIMS: Recommendations for programming the rate-adaptive AV delay in CRT. METHODS AND RESULTS: In cases of continual biventricular pacing, the optimal AV delay in CRT (AVD(opt)) is the net effect of the pacemaker-related interatrial conduction time (IACT), duration of the left-atrial electromechanical action (LA-EAC(long)), and the duration of the left-ventricular latency period (S(V)-EAC(short)). It can be calculated by AVD(opt) = IACT+LA-EAC(long)-S(V)-EAC(short). We measured these three components in 20 CRT-ICD patients during rest and submaximal ergo metric exercise (71 +/- 9 W) resulting in a 22.5 +/- 9.6 bpm rate increase. IACT and S(V)-EAC(short) did not reveal significant differences. LA-EAC(long), however, varied significantly by -10.7 +/- 16.1 ms (P = 0.008) during exercise. In contrast to AVD(optVDD), there was a significant difference in AVD(optDDD) of -8.8 +/- 14.5 ms (P = 0.014) between the resting and submaximal exercise conditions. In DDD pacing, AVD(opt) was shortened by 2.6 ms/10 bpm. CONCLUSION: In consideration of the findings of the studies performed to date, the rate-adaptive AV delay should be deactivated.

Current role of endovascular therapy in Marfan patients with previous aortic surgery.

The Marfan syndrome is a heritable disorder of the connective tissue which affects the cardiovascular, ocular, and skeletal system. The cardiovascular manifestation with aortic root dilatation, aortic valve regurgitation, and aortic dissection has a prevalence of 60% to 90% and determines the premature death of these patients. Thirty-four percent of the patients with Marfan syndrome will have serious cardiovascular complications requiring surgery in the first 10 years after diagnosis. Before aortic surgery became available, the majority of the patients died by the age of 32 years. Introduction in the aortic surgery techniques caused an increase of the 10 year survival rate up to 97%. The purpose of this article is to give an overview about the feasibility and outcome of stent-graft placement in the descending thoracic aorta in Marfan patients with previous aortic surgery.

NMR at pressures up to 90 GPa.

The past 15 years have seen an astonishing increase in Nuclear Magnetic Resonance (NMR) sensitivity and accessible pressure range in high-pressure NMR experiments, owing to a series of new developments of NMR spectroscopy applied to the diamond anvil cell (DAC). Recently, with the application of electro-magnetic lenses, so-called Lenz lenses, in toroidal diamond indenter cells, pressures of up to 72 GPa with NMR spin sensitivities of about 1012 spin/Hz1/2 has been achieved. Here, we describe the implementation of a refined NMR resonator structure using a pair of double stage Lenz lenses driven by a Helmholtz coil within a standard DAC, allowing to measure sample volumes as small as 100 pl prior to compression. With this set-up, pressures close to 100 GPa could be realised repeatedly, with enhanced spin sensitivities of about 5 × 1011 spin/Hz1/2. The manufacturing and handling of these new NMR-DACs is relatively easy and straightforward, which will allow for further applications in physics, chemistry, or biochemistry.

Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI).

BACKGROUND: Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man. METHODS AND RESULTS: Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control). CONCLUSIONS: G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.

Percutaneous endovascular repair of aneurysm after previous coarctation surgery.

BACKGROUND: Formation of aortic aneurysm late after surgical repair of coarctation carries a significant risk of rupture and lethal outcome, and repeat surgery is associated with a 14% in-hospital mortality rate and morbidity from paraplegia, injury to the central nervous system, or from bleeding. The potential of nonsurgical endovascular repair by the use of stent-grafts in lieu of repeat surgery for postcoarctation aneurysm is unknown. METHODS AND RESULTS: The concept of postsurgical endovascular stent-graft placement was evaluated with respect to feasibility and safety in 6 consecutive patients with late aneurysm formation after coarctation repair. All patients had aneurysm formation late after patch aortoplasty; placement of an elephant trunk during surgical repair of secondary type I dissection preceded formation of a local aneurysm in 2 cases. Patient age was 49+/-12 years, ranging from 31 to 68 years. Transluminal placement of customized stent-grafts was successful, with no 30-day or 1-year intervention-related mortality or morbidity. Follow-up survey of 11 to 47 months revealed optimal reconstruction of the thoracic aorta; 1 patient died 11 months after endovascular repair from cancer. CONCLUSIONS: Nonsurgical aortic reconstruction of postsurgical thoracic aneurysms forming late after coarctation repair is safe and feasible; interventional stent-graft placement has the potential to avoid repeat surgery of postsurgical aortic aneurysm.

[Treatment of acute ST Elevation myocardial infarction in a regional network ("Drip & Ship Network Rostock")]. / Behandlung des akuten ST-Hebungsinfarkts in Netzwerkstrukturen: "Drip&Ship -- das Rostocker Infarktmodell".

Management of acute ST elevation myocardial infarction (STEMI) demands rapid and complete reperfusion of the infarct-related artery (IRA). With postinfarction prognosis depending on time delay from onset of symptoms to complete reperfusion (TIMI 3 flow) of the IRA, primary percutaneous coronary intervention (PPCI) performed by an experienced team has been shown to be superior to thrombolytic therapy with lower mortality, less frequent occurrence of nonfatal reinfarction and stroke, and thus represents the preferred treatment strategy according to the national and international guidelines. For regional implementation of PPCI, particularly in rural areas, information and transfer logistics within networks of care and direct transport of an infarction patient to a PCI hospital rather than to the closest hospital are a challenge. With successful implementation of network logistics and standardized therapeutic pathways, current guidelines and requested timelines versus thrombolysis could be met. The implemented logistics comprised 24 h/7 days stand-by services of an experienced PCI team, direct telephone hotline contact between rescue service/emergency physician and interventional cardiologist on call, and direct open access to a catheterization laboratory at any time. Within the Drip&Ship network Rostock, to date (July 2007) 1,022 consecutive patients with PCI for STEMI were documented and analyzed over 5 years; of these, 490 patients were transferred from a community hospital to the PCI center and 532 patients were admitted directly to the interventional center. In 95.1% of all transferred and in 94.8% of all directly admitted patients, PCI was successfully accomplished upon arrival. A normalized flow to the IRA after PCI was documented in 96% of both groups, no patient was subjected to thrombolytic therapy. At 12-month follow-up, there were no differences between both groups with respect to infarct size and mortality. Moreover, there was no evidence of differences in left ventricular ejection fraction between groups. Thus, transportation of STEMI patients within an established PCI network did not result in any prognostic disadvantage. Efficient network logistics with transportation for PPCI in acute STEMI ensure both safety and outcome profiles similar to patients treated by PCI in metropolitan areas.

How can the rate-adaptive atrioventricular delay be programmed in atrioventricular block pacing?

AIM: To optimize recommendations for programming of the rate-adaptive atrioventricular (AV) delay. METHODS AND RESULTS: Optimal AV delay (AVD(opt)) is the net effect of the pacemaker-related interatrial conduction time (IACT), duration of the left-atrial electromechanical action (LA-EAC(long)) and duration of left-ventricular latency (S(V)-EAC(short)). It can be calculated by AVD(opt) = IACT + LA-EAC(long)-S(V)-EAC(short). We measured these three components in 20 DDD pacemaker patients (EF >45%) with the third degree AV block (AVB) at rest and submaximal ergometric exercise load of 71 +/- 9 W which resulted in a 31.5 +/- 9.9 bpm rate increase. Between exercise and rest, the components of and the final AVD(opt) showed no significant differences. Interatrial conduction time in VDD and DDD pacing varied by 2.3 +/- 8.4 ms and 1.4 +/- 8.8 ms, respectively, S(V)-EAC(short) changed by -2.6 +/- 21.8 ms and AVD(opt) by -3.5 +/- 33.3 ms and -4.3 +/- 37.8 ms in VDD and DDD operation, respectively. The greatest variation was of LA-EAC(long) by -8.4 +/- 32.7 ms. Linear regressions of the rate-dependent variations (Deltaf) in VDD operation yielded DeltaIACT(f) = 0.04Deltaf + 0.95 ms, DeltaLA-EAC(long) = -0.59Deltaf + 10.1 ms, and DeltaS(V) - EAC(short) = 0.14Deltaf -7.2 ms which resulted in DeltaAVD(opt) = -0.69Deltaf + 18.2 ms. CONCLUSION: A recommendation for programming of rate-adaptive AV delay in AV block patients cannot be given.

Interventional closure with Amplatzer PFO occluder of patent foramen ovale in patients with paradoxical cerebral embolism.

Percutaneous transcatheter closure has been proposed as an alternative to surgical closure or long-term anticoagulation in patients with presumed paradoxical embolism and patent foramen ovale (PFO). We report our mid-term results of 55 consecutive symptomatic patients (mean age: 47 years, range: 20-79) who underwent percutaneous transcatheter closure of PFO after at least one event of cerebral ischemia; 16 (29%) patients had at least one transient ischemic attack and 39 (71%) patients at least one embolic stroke. Multiple embolic events had occurred in 6 (11%) patients. Percutaneous transcatheter closure was technically successful in all 55 patients (100%). For the majority of patients, an Amplatzer PFO occluder measuring 25 mm in diameter (n=49) or an Amplatzer PFO occluder measuring 35 mm in diameter (n=6) was used. Complete occlusion by color Doppler and transesophageal contrast echocardiography investigation was achieved in 96% at follow-up 3-6 months after implantation; only 2 patients had a trivial residual shunt at follow-up. Mean fluoroscopy time was 6.7 minutes (range: 1.7-47.1), and in-hospital follow-up was uneventful except for 1 patient who developed a cardiac tamponade requiring uneventful and successful needle pericardiocentesis. At a mean follow-up of 19 months (range: 3-32) no recurrent embolic neurological events was observed. Transcatheter closure of PFO with Amplatzer PFO occluder devices is a safe and effective therapy for patients with previous paradoxical embolism and aneurysmatic or nonaneurysmatic PFO. Percutaneous closure is associated with a high success rate, low incidence of hospital complications, and freedom of cerebral ischemia events.

Intentional occlusion of the left subclavian artery during stent-graft implantation in the thoracic aorta: risk and relevance.

PURPOSE: To examine the clinical consequences and/or potential need for postinterventional transposition after stent-graft occlusion of the left subclavian artery (LSA). METHODS: The records of 171 consecutive patients (128 men; mean age 60.2+/-13.2 years, range 20-83) undergoing elective stent-graft repair in the thoracic aorta were reviewed to identify intentional endograft coverage of the ostial LSA, as documented by transesophageal echocardiography and/or aortography. Patients were treated for subacute type B dissection, true aneurysm, pseudoaneurysm, or previously operated type A dissection with persistent false lumen flow in the descending aorta. Among the 171 cases, 22 (12.9%) patients were identified with stent-graft occlusion of the LSA. RESULTS: A systolic blood pressure differential existed between the right (138.4+/-14.0 mmHg) and the left (101.8+/-21.0 mmHg; p<0.05) arms after occlusion of the LSA. No patient showed a malperfusion syndrome during postinterventional hospitalization. During a mean follow-up of 24.0+/-15.8 months, 15 (68.2%) patients remained completely asymptomatic, with no functional deficit or temperature differential between the arms, while 7 patients reported mild symptoms of a subclavian steal syndrome. However, no patient required any secondary surgical intervention. CONCLUSIONS: Stent-graft-induced occlusion of the ostial LSA was tolerated by all patients without chronic functional deficit. In the absence of stenotic vertebral and/or carotid arteries and with a documented intact vertebrobasilar system, prophylactic transposition of the LSA is not required prior to intentional stent-graft occlusion of the LSA.