Ventricular fibrillation-induced intracellular Ca2+ overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation

Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca2+]i overload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca2+]i transients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca2+]i during VF (by increasing [Ca2+]o from 3 to 6 mM) increased the defibrillation threshold (DFT) from 1.9 +/- 0.6 to 3.5 +/- 0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6 +/- 7.7 to 48.6 +/- 7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca2+]i (r=0.69 and 0.83, P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca2+]i overload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca2+]i overload (-115 +/- 3%). In contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]i overload after initially successful shocks were often followed by synchronized spontaneous [Ca2+]i oscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca2+]i overload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca2+]i overload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.     

Tissue reactions to bacteria-challenged implantable leads with enhanced infection resistance

Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3 1/2, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials.     

Continuous purification of porcine lipase by rotating annular size-exclusion chromatography

Non-accidental head injury, be it shaking, impact(s) or a combination of the two, is characterised by subdural and/or subarachnoid haemorrhages with retinal haemorrhages, but minimal or absent external cranio-facial trauma. The classical assault scenario depicts the infant being gripped around the head, face, chest and abdomen and shaken or being gripped by a limb and swung. This gripping might be expected to leave physical evidence in the form of bruising. A study was undertaken to establish the prevalence, distribution and pathological association of external bruising in 24 cases of fatal non-accidental head injury in children. At autopsy, 17 cases had new external bruises, 15 old external bruises and 13, a combination of both. However, seven (29%) cases showed no fresh external bruising and five (21%) showed no external bruising at all. Thus, external bruising may be absent in children with fatal intracranial injury. The face was shown to be the commonest site of bruising followed by the forehead and buttocks. Limb, chest and abdominal bruising were found to be uncommon. Retinal haemorrhages were confirmed in 23 (96%) cases. It is hypothesised that bruising, when present, may be a result of abuse in the form of punches and slaps rather than due to gripping during the assault. We discuss why gripping does not necessarily result in external bruising.     

Does arterial revascularization decrease the risk of infarction after coronary artery bypass grafting?

BACKGROUND: This study sought to determine whether extensive arterial grafting reduces the prevalence and consequences of infarct after coronary artery bypass grafting. METHODS: Post-primary coronary artery bypass grafting infarcts and time-related events thereafter were identified by 99.9% complete follow-up of 9,600 patients (1971 to 1992). The contribution of arterial grafting to freedom from infarct was assessed by multivariable hazard function analysis to adjust for other risk factors. RESULTS: Unadjusted 1-month and 10-year freedom from infarction was 97% and 86%. By multivariable analysis, arterial grafting lowered the prevalence of periprocedural (p = 0.005), intermediate term (p = 0.007 and 0.006), and late infarction (arterial grafting to the left anterior descending coronary artery, p = 0.0006). Unadjusted survival after first infarct after coronary artery bypass grafting was 74% and 52% at 1 and 10 years; arterial grafting improved 10-year survival from 48% to 59% (p = 0.002). An additional benefit or cost of extending arterial grafting (n = 1,727) beyond a single one could not be identified (p > 0.1). CONCLUSIONS: Arterial conduits, particularly to the left anterior descending coronary artery, should be used for coronary artery bypass grafting to reduce early and late myocardial infarction and its consequences. However, use of more than a single arterial graft appears to confer no additional benefit.     

Cognitive ability and cerebral lateralisation in transsexuals

INTRODUCTION: The application of high-frequency current to the AV junctional area results in a temperature rise in the myocardium and may cause accelerated junctional rhythm (AJR). The aim of the study was to characterize heat-induced AJR in an in vitro animal model. METHODS AND RESULTS: Studies were performed in isolated perfused pig and rabbit hearts. Using a small heating probe, we could induce AJR from a discrete area located in the middle of the triangle of Koch, which was smaller than the area from which RF energy application could elicit AJR. Histology showed that the heat-sensitive area was located over, or close to, the compact AV node. It did not correspond with the areas where double potentials were found or with the site(s) of earliest atrial activation during VA conduction. Microelectrode recordings revealed that AJR arose in nodal-type cells. Heat increased the slope of the phase 4 depolarization and shortened the action potential duration. Two types of AJR were observed: the first one was regular and the second one showed irregularity in the intervals. Interaction of multiple foci and the presence of conduction block between the foci and the His bundle caused the irregularity of the His-His intervals during the second type of AJR. CONCLUSION: AJR observed during heat and RF application in the AV nodal area results from the effect of heat on AV nodal cells with underlying pacemaker activity. The heat-sensitive area is located over, or very close to, the compact AV node.     

Mathematical models for motile bacterial transport in cylindrical tubes

Mathematical models considering motile bacterial transport within a geometrically restrictive cylindrical tube were developed. Two macroscopic transport parameters, the random motility coefficient as a self-diffusion coefficient of the cell population and the chemotactic velocity as a chemical-induced velocity, were derived. The three-dimensional cell balance equation was reduced to forms similar to Segel's one-dimensional phenomenological cell balance equations with additional modifications for bacteria-wall interactions. Two conceptually different approaches accounting for such interactions were presented. The first approach parallels treatments in the gas kinetic theory by viewing bacterial interactions with walls as collisions and subsequent diffusive/specular reflections, which led to the Bosanquet formula for the bacterial diffusion coefficient. Based on the experimental observation that bacterial swimming motion is guided by a straight tube, the second approach considered modifications in the bacterial swimming orientation as a consequence of various long-range interactions with the tube surface. A phenomenological turning model capable of aligning bacterial motion along a tube axis was proposed. The model predicts that under the geometrical restriction of a small cylindrical tube, the macroscopic bacterial transport resulting from the proposed turning model can exhibit behavior that ranges from dimensionally reduced diffusion to pure wave propagation, depending on the influence of the tube diameter on the reversal probability in the bacterial swimming motion. Our theoretical model provides explicit equations that explain how such a transition can occur. The predicted results were then qualitatively compared with experimental data from the literature. As a preliminary comparison, we concluded that bacterial transport in cylindrical tubes of diameter 10 micrometers remains in the mode of a dimensionally reduced diffusion, and shifts to a wave motion when the tube diameter decreases to 6 micrometers.     

Fish as models for the neuroendocrine regulation of reproduction and growth

Models are essential for the full understanding of neuroendocrine control processes. In this regard fish offer a rich source of biological material. They have diverse growth and reproductive strategies, inhabiting most of the Earth's aquatic ecological niches. Fish possess many of the common vertebrate features but also offer several unique aspects to allow the biologist easy access to the study of hypothalamic and pituitary function. Several key examples of how teleosts, or the bony fish, can offer insight into fundamental mechanisms of vertebrate sex differentiation, growth and reproduction are reviewed.     

Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.     

Metastatic carcinoma of the prostate mimicking primary carcinoid tumor of the lung and mediastinum

AIMS: To investigate the current use of thrombolytic therapy in the management of patients with acute myocardial infarction and to determine the potential for an increased use of thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: All hospitalised cases of acute myocardial infarction were identified in three health districts in the UK (population of 960,000) in patients under the age of 76 years during a 2-year period; 2439 patients had acute myocardial infarction, of whom 1264 (52%) received thrombolytic therapy. Failure to administer thrombolytic therapy was a result of the absence of diagnostic electrocardiograms in 712 (29.2%) patients, late presentation in 127 (5.2%), therapeutic error in 112 (4.6%), presence of a bleeding risk in 139 (5.7%) and other miscellaneous reasons in 80 (3.3%) patients. Thirty-eight of the 139 patients in whom bleeding risk was reported as a contra-indication could, in retrospect, have received thrombolytic therapy and a further 76 would have been suitable for primary PTCA. CONCLUSIONS: The potential for increasing the use of thrombolytic therapy seems to be limited and is unlikely to make a major impact on the in-hospital mortality from acute myocardial infarction. However, primary PTCA should be considered in those who are ineligible for thrombolysis because of bleeding risk as a contra-indication.