Ca2+‐Binding Proteins in Dogs with Heart Failure: Effects of Cardiac Contractility Modulation Electrical Signals

Background: In dogs with heart failure (HF), chronic therapy with cardiac contractility modulation (CCM) electrical signals delivered to left ventricular (LV) muscle during the absolute refractory period improves LV function. This study examined the effects of CCM therapy on the expression of calcium (Ca²⁺)‐binding proteins (CBPs) in dogs with HF. Methods and Results: Studies were performed in LV tissue from seven CCM‐treated HF dogs, seven untreated HF dogs, and six normal (NL) dogs. mRNA expression of S100A1, sorcin, presenillin‐1 (PS1), PS2, histidine‐rich Ca²⁺‐binding protein (HRC), and 18S ribosomal RNA (18S), a housekeeping gene, was measured using RT‐PCR. Protein levels of CBPs and calsequestrin (CSQ) were determined by Western blotting. No difference was observed in the expression of 18S and CSQ among study groups. Compared with NL, the expression of S100A1, sorcin, and HRC was decreased, whereas the expression of PS2 was increased in untreated HF dogs. CCM therapy normalized the expression of S100A1, sorcin, and PS2 but not of HRC. No change was seen in the expression of PS1 among study groups. Conclusion: CCM therapy restores LV expression of S100A1, PS2, and sorcin. Normalization of CBPs may partly contribute to improved LV function in HF following CCM therapy.     

Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients

From May 2007 to January 2008, patients with Stage 3‐5 chronic kidney disease (CKD) undergoing gadobenate dimeglumine (GBD)‐enhanced magnetic resonance (MR) examinations were included in the retrospective investigation. The electronic medical records were reviewed to assess the prevalence of nephrogenic systemic fibrosis (NSF) in renally impaired patients underwent GBD‐enhanced MR examinations. In all, 250 patients (98 men, mean age 72.6 years) were included: 97% of the patients had Stage 3 CKD (estimated GFR 30–59 mL/min/1.73 m²); 37% had been exclusively exposed to GBD. The remaining were exposed to GBD and other gadolinium‐based contrast agents (GBCAs). The mean dose of GBD was 22 mL (standard deviation [SD], 11.2). Including exposure to other GBCAs, the mean cumulative dose of gadolinium was 61 mL (SD, 62.3). A total of 206 patients (82%) had skin examinations following the last GBD administration (mean duration, 108 days). No evidence of suspected or diagnosed NSF was found. In conclusion, on the basis of a retrospective chart review there was no skin evidence of NSF in predominantly Stage 3 CKD patients who were exposed to GBD at an average follow‐up of 108 days, either solely or in combination with other GBCAs. J. Magn. Reson. Imaging 2009;30:1335–1340. © 2009 Wiley‐Liss, Inc.     

Zentrale Notfallaufnahme des Universitätsklinikums Köln im Verbund des städtischen Rettungswesens

Zusammenfassung Das Klinikum der Universit?t zu K?ln führt seit einem Jahrzehnt eine Zentrale Notaufnahme (ZNA). Sie ist zust?ndig für j?hrlich ca. 16.000 Notfallpatienten, die privat das Klinikum aufsuchen, und für ca. 3.000 Patienten, die mit Rettungsmitteln über die Berufsfeuerwehr K?ln und Umgebung per bodengebundenem (KTW, RTW und RTW mit Notarzt) oder luftgestütztem (RTH) Transport über den Dachlandeplatz eingeliefert werden. Darüber hinaus stellt das Personal der ZNA das hausinterne Rettungsteam und einen Notarzt für den ?ffentlichen Rettungsdienst der Stadt K?ln. Die Gesch?ftsleitung und Koordination der ZNA obliegt der Klinik für An?sthesiologie und Operative Intensivmedizin. Die Versorgung erfolgt je nach Erkrankung durch ein interdisziplin?res Team aus An?sthesiologen, Unfallchirurgen, Viszeralchirurgen, Neurochirurgen, Mund-, Kiefer-, Gesichtschirurgen, Internisten, Dermatologen und Radiologen. So beinhaltet das linksrheinische Notfallzentrum des Klinikum der Universit?t zu K?ln das gesamte Spektrum notfallmedizinischer M?glichkeiten mit Notarztdienst, zentraler Anfahrt für Rettungswagen, Hubschrauberlandeplatz, 3 Schockr?umen, Notfallradiologie mit CT-Diagnostik und unmittelbarer N?he zum Operationsbereich und zu den Intensivstationen.     

Current and emerging drug treatment strategies for peripheral arterial disease

ABSTRACT

Introduction

Peripheral artery disease (PAD) is a prevalent but underdiagnosed manifestation of atherosclerosis that has a worse prognosis than coronary artery disease. Patients with PAD are at heightened risk of both systemic cardiovascular adverse events and limb-related morbidity. There is insufficient awareness of its clinical manifestations, including intermittent claudication and critical limb ischemia and of its risk of adverse cardiovascular and limb outcomes.     

The Clinical Dilemma of Quantifying Mechanical Left Ventricular Dyssynchrony for Cardiac Resynchronization Therapy: Segmental or Global?

Heart failure (HF) represents a serious clinical and public cause of mortality, morbidity, as well as healthcare expenditures. Guidelines for treatment of HF join in recommending multimedical regimen at targeted doses as the best medical strategy, despite that a significant percentage of patients remain symptomatic. Studies have shown that these patients might benefit from cardiac resynchronization therapy (CRT), particularly those presenting with broad QRS duration, >135 msec. Trials have already shown that CRT results in improved morbidity and survival of these patients particularly those in New York Heart Association class III–IV HF, but almost 30% do not show any symptomatic or survival benefit, hence are classified as nonresponders. Exhaustive efforts have been made in using noninvasive methods of assessing left ventricle (LV) dyssynchrony in predicting nonresponders to CRT, including Doppler echocardiography, magnetic resonance imaging, and even single photon emission computed tomography analysis, but only with modest success. In this report, we aimed to review the available evidence for assessing markers of mechanical LV dyssynchrony by various echocardiographic modalities and their respective strength in predicting favorable response to CRT treatment, comparing global with segmental ones. While the accuracy of segmental markers of dyssynchrony in predicting satisfactory response to CRT remains controversial because of various technical limitations, global markers seem easier to measure, reproducible, and potentially accurate in reflecting overall cavity response and its clinical implications. More studies are needed to qualify this proposal.     

A brief history of tendon and ligament bioreactors: Impact and future prospects

Bioreactors are powerful tools with the potential to model tissue development and disease in vitro. For nearly four decades, bioreactors have been used to create tendon and ligament tissue-engineered constructs in order to define basic mechanisms of cell function, extracellular matrix deposition, tissue organization, injury, and tissue remodeling. This review provides a historical perspective of tendon and ligament bioreactors and their contributions to this advancing field. First, we demonstrate the need for bioreactors to improve understanding of tendon and ligament function and dysfunction. Next, we detail the history and evolution of bioreactor development and design from simple stretching of explants to fabrication and stimulation of two- and three-dimensional constructs. Then, we demonstrate how research using tendon and ligament bioreactors has led to pivotal basic science and tissue-engineering discoveries. Finally, we provide guidance for new basic, applied, and clinical research utilizing these valuable systems, recognizing that fundamental knowledge of cell-cell and cell-matrix interactions combined with appropriate mechanical and chemical stimulation of constructs could ultimately lead to functional tendon and ligament repairs in the coming decades.