Antiarrhythmic management and implantable defibrillator use in survivors of prehospital cardiac arrest without myocardial infarction in West Yorkshire.

OBJECTIVE: To explore the current use of secondary preventive treatment in survivors of out of hospital cardiac arrest without myocardial infarction (primary ventricular tachycardia/ventricular fibrillation (VT/VF)) in West Yorkshire, and assess the implications of recent studies on the benefits of implantable cardioverter-defibrillators (AICD) in this context. DESIGN: Retrospective analysis of an ambulance service based database of outcome after resuscitation of out of hospital cardiac arrest and the Leeds AICD implantation database. MAIN OUTCOME MEASURES: Mortality, rate of referral for specialist investigation, antiarrhythmic treatment. RESULTS: Twelve month mortality following successful discharge after primary VF arrest was 15%. Of 53 patients with primary VF/VT, 29 apparently did not see a cardiologist during the initial admission. Amiodarone was the most widely used antiarrhythmic agent. Six patients (15%) received an AICD. During the same period 22 patients from the same catchment area received an AICD following an in-hospital cardiac arrest. CONCLUSIONS: Mortality among survivors of non-infarct related prehospital cardiac arrest remains significant, with few patients being referred for specialist investigation. The implementation of recent guidelines on AICD use in cardiac arrest survivors would have resulted in an approximate 60% increase in the total numbers of defibrillators implanted in the West Yorkshire area.

Tip-link organization in anomalously-oriented hair cells of the guinea pig cochlea.

Stereocilia are described in a group of guinea pigs with abnormal conformation of the outer hair cell stereociliary bundles. Rows of stereocilia were found which were circular instead of V- or W-shaped, and rotated or even reversed in orientation with respect to normal. The stereocilia have however a normal gradation in heights of the rows of stereocilia, and have tip links running in the direction of gradation in height.

South Asians are Under-Represented in a Clinic Treating Atrial Fibrillation in a Multicultural City in the UK.

The Leeds rapid access atrial fibrillation (AF) clinic was set up to streamline and standardise management of patients with newly diagnosed AF. Anecdotal evidence suggests that there is under-representation of south Asians in these clinics.All patient attendances between June 2007 and June 2011 were documented and combined with ethnicity data from patient administration records. Local population demographics for 2009 were obtained from the office of national statistics. This was used to estimate the expected prevalence of AF across the different ethnic groups in Leeds taking age into account. One thousand two hundred and ten patients were referred. The study sample included 992 patients, and the number of south Asians attending was 88% less than expected (Chi squared analysis; p<0.0001). These results suggest that there is an under-representation of south Asians in a large centre that serves a cosmopolitan population. Potential reasons for this discrepancy including barriers to accessing treatment for this population or a lower prevalence of AF in south Asians due to an as yet unidentified genetic factor.

Two-dimensional strain imaging: a new echocardiographic advance with research and clinical applications.

Over the past two decades the quest for quantitative evaluation of left ventricular function and regional wall motion has escalated, allowing several aspects of myocardial contractile patterns to be quantified, both during stress echocardiography and in the assessment of dyssynchrony. Most of the literature to date has used Tissue Doppler Imaging (TDI) techniques to assess essentially long-axis function due to the angle dependency of Doppler based techniques. This brief review introduces the early development, validation and potential clinical applications of a new technique of quantifying two-dimensional (radial and circumferential) strains and strain rates through tracking myocardial "speckles". In-vivo and in-vitro validation of this 2D-strain imaging technique has been undertaken and reached a point where it is considered ready for more widespread investigations into clinical utility. One important advantage over TDI techniques is that it is not limited by dependency on the angle of insonation. Several recent studies looking at ventricular function in specific groups of patients have reported practical ability to distinguish the abnormally from the normally contracting regions of ventricular walls. It provides new and complementary quantitative information about ventricular dyssynchrony and regional wall motion abnormalities. More research studies are needed to determine the sensitivity and specificity of the measurements obtained using this technique and define its strengths and limitations. In particular, whether the measured values correlate well with clinical outcomes will need to be established in longitudinal interventional studies. The clinical utilities of this technique over the coming years are likely to expand rapidly.

Orthostatic changes in AV node conduction causing dizziness during paroxysmal atrial tachycardia.

Dizziness in the upright posture is a common reason to seek medical advice and is often dismissed as benign orthostatic hypotension. We present an unusual case of dizziness in the upright posture due to possible changes in atrioventricular nodal conduction during atrial tachycardia.

Issues in the culture of the extremely thermophilic methanogen, Methanothermus fervidus.

Basic issues in the culture of the extremely thermophilic archaeon, Methanothermus fervidus, have been investigated, including culture medium formulation, substrate yield and product yield coefficient, growth rate and stoichiometry, and H(2) uptake kinetics. The pH optimum for growth of this organism was estimated at 6.9. Growth medium buffered with PIPES instead of bicarbonate supported both increased growth rate and maximum biomass concentration. Substitution of titanium(III) citrate for the reducing agent sodium sulfide improved culture performance as well. However, independent adjustment of iron and nickel concentrations from 11 to 111 microM, respectively, and carbon dioxide partial pressure from 5 to 20 psia did not impact the culture of M. fervidus significantly. An elemental balance approach was utilized to aid in design of a defined medium to support growth to a target maximum biomass concentration of at least 1.0 g dry wt/L. The growth of this organism was limited by H(2) availability in this reformulated culture medium. The maximum growth rate and biomass concentration achieved in anaerobic vials with the defined medium was 0.16 h(-1) and 0.74 g dry wt/L, respectively. This maximum biomass concentration was a 72% improvement over that obtained with a literature-based defined medium. The Monod parameter, K(s), with H(2) as limiting substrate, was estimated at 1.1 +/- 0.4 psia (55 +/- 20 microM in the broth), based on a H(2) consumption study. Representative values for the substrate yield, Y(X/CO(2) ), and product yield coefficient, Y(CH(4)/) (X), were determined experimentally to be 1.78 +/- 0.04 g dry wt/mol CO(2), and 0.52 +/- 0.01 mol CH(4)/g dry wt, respectively. A bench-scale fermentation system suitable for the culture of extremely thermophilic anaerobes was designed and constructed and proved effective for the culture of M. fervidus.

Use of a long preshaped sheath to facilitate cannulation of the coronary sinus at electrophysiologic study.

INTRODUCTION: Catheterization of the coronary sinus (CS) from the femoral vein can be challenging. We tested whether use of a long preshaped sheath facilitates CS cannulation. METHODS AND RESULTS: One hundred four patients were randomized into two phases. In phase 1, consecutive patients were allocated to CS catheterization using the long sheath (n = 26) or standard 7-French 15-cm sheath (n = 25). If unsuccessful within 10 minutes, the alternative technique was used. Phase 2 assessed the utility of the long sheath in difficult cases. All patients initially were approached using the standard sheath. If cannulation failed after 10 minutes, patients were randomly allocated to the standard or long sheath approach. In phase 1, the standard approach failed in 4 (16%) of 25 cases. In each case, a long sheath proved successful (mean 3.2 min). The long sheath approach was successful within 10 minutes in all 26 cases. Catheter deployment was significantly quicker with the long sheath, but this was offset by the time required for sheath insertion. In phase 2, the standard approach was successful in 46 (87%) of 53 cases. Of 7 "failures," 3 were randomized to continue the standard approach, which was successful in 1; 4 were randomized to the long sheath approach, and success was achieved in all (mean 4.4+/-1.5 min). Overall, the CS could not be promptly catheterized in 15% of cases within 10 minutes using the standard sheath, and no failures were seen using the long sheath. No complications arose from the use of either technique. CONCLUSION: The long sheath was uniformly successful in permitting catheterization of the CS from the femoral approach in both unselected and difficult cases.

Endothelial inhibition of myofilament calcium response in intact cardiac myocytes.

Recent studies suggest that factors released by endothelial cells can modify contraction of isolated cardiac preparations. We compared the effects of 1) coronary effluent collected from Langendorff-perfused rat hearts and 2) cultured vascular endothelial cell superfusate on isolated fura 2-loaded rat ventricular cardiac myocytes. Coronary and cultured cell effluent produced similar effects. Isotonic contraction amplitude was reduced by 31.6 +/- 2.6 and 70.2 +/- 9.1%, respectively; myocyte diastolic length increased by 0.8 +/- 0.2 and 1.5 +/- 0.4 microns, and time to 50% relaxation fell by 6.2 +/- 1.8 and 10.1 +/- 2.0% (all P < 0.05; n = 29 and 15 myocytes, respectively). A small fall in the amplitude of the intracellular Ca2+ transient was observed (8.5 +/- 1.5 and 10.9 +/- 3.5%, respectively; both P < 0.01), insufficient to account for the reduction in twitch amplitude. In intact myocytes tetanized in the presence of thapsigargin, the steady-state myofilament response to Ca2+ was reduced by coronary and cultured cell effluent. These results suggest that both coronary endothelial cells in situ and cultured endothelial cells tonically release a factor(s) that reduces myofilament Ca2+ response.

The cardiac endothelium: cardioactive mediators.

Endothelial cells within the heart release a number of substances that modulate myocardial contractile function. These agents include nitric oxide, endothelin, prostanoids, adenylpurines, and other substances that have so far been characterized only in bioassay studies. A notable feature of many of these agents is that they influence contractile behavior predominantly by modifying cardiac myofilament properties rather than altering cytosolic Ca2+ transients. A consequence of this subcellular action is often a disproportionate effect on myocardial relaxation and diastolic tone. The paracrine modulation of cardiac myocyte function by endothelial cell factors is likely to be an important mechanism contributing to the overall regulation of cardiac contractile function, both physiologically and in pathological states.

Inhibition of myocardial crossbridge cycling by hypoxic endothelial cells: a potential mechanism for matching oxygen supply and demand?

Previous studies have shown that cardiac endothelial cells release substances that influence myocardial contraction. Since PO2 is an important stimulus that modulates endothelial function, we investigated the effects of acute moderate hypoxia and reoxygenation on the release of cardioactive factors by endothelial cells. Endothelial cells cultured from several vascular beds were superfused with normoxic (equilibrated with room air; PO2, approximately 160 mm Hg) or hypoxic (PO2, 40 to 50 mm Hg) physiological buffer solution, and the superfusates were reequilibrated to a PO2 of approximately 160 mm Hg and then tested for their effects on various myocardial assays. Endothelial cell viability and buffer ionic composition were unaltered after the superfusion procedures. The superfusates of hypoxic endothelial cells induced rapid, potent, reversible inhibition of isolated cardiac myocyte contraction without reducing cytosolic Ca2+ transients. This activity was not lost after heating (95 degrees C) and was present in low molecular weight (Mr, <500) superfusate fractions. Hypoxic endothelial superfusate reduced unloaded shortening velocity of human skinned soleus muscle fibers. It markedly depressed in vitro actin motility over cardiac myosin and reduced the rate of actin-activated cardiac myosin ATPase activity but had no effect on corresponding smooth muscle myosin assays. Reoxygenation of hypoxic endothelial cells resulted in loss of this inhibitory activity. These data indicate that cultured endothelial cells respond to acute moderate hypoxia by releasing an unidentified substance(s) that inhibits myocardial crossbridge cycling, independent of Ca2+ or other second messenger signaling pathways. Such a mechanism could have important implications for the regulation of oxygen supply-demand balance in the heart and be relevant to conditions such as myocardial hibernation.