Right Ventricular Septal Pacing: A Comparative Study of Outflow Tract and Mid Ventricular Sites

Background: Prolonged right ventricle (RV) apical pacing is associated with left ventricle (LV) dysfunction due to dysynchronous ventricular activation and contraction. Alternative RV pacing sites with a narrower QRS compared to RV pacing might reflect a more physiological and synchronous LV activation. The purpose of this study was to compare the QRS morphology, duration, and suitability of RV outflow tract (RVOT) septal and mid‐RV septal pacing. Methods: Seventeen consecutive patients with indication for dual‐chamber pacing were enrolled in the study. Two standard 58‐cm active fixation leads were passed to the RV and positioned in the RVOT septum and mid‐RV septum using a commercially available septal stylet (model 4140, St. Jude Medical, St. Paul, MN, USA). QRS duration, morphology, and pacing parameters were compared at the two sites. The RV lead with less‐satisfactory electrical parameters was withdrawn and deployed in the right atrium. Results: Successful positioning of the pacing leads at the RVOT septum and mid‐RV septum was achieved in 15 patients (88.2%). There were no significant differences in the mean stimulation threshold, R‐wave sensing, and lead impedance between the two sites. The QRS duration in the RVOT septum was 151 ± 14 ms and in the mid‐RV septum 145 ± 13 ms (P = 0.150). Conclusions: This prospective observational study shows that septal pacing can be reliably achieved both in the RVOT and mid‐RV with active fixation leads using a specifically shaped stylet. There are no preferences in regard to acute lead performance or paced QRS duration with either position. (PACE 2010; 33:1169–1173)     

Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

The pandemic H1N1 2009 influenza virus has caused the first influenza pandemic of the 21st century, leading to disproportionate fatalities in the low-risk population despite the generally mild nature of the illness. Advances in sci     

Malaysian Dialysis and Transplant Registry Report

This report summarizes data for dialysis and transplant patients up to the end of 1995. We estimate coverage to be about 30% of dialysis patients and near complete ascertainment of transplant patients. On the 31 December 1995, there were 2224 patients on renal replacement therapy (RRT), comprising 50% on haemodialysis (HD), 12% on continuous ambulatory peritoneal dialysis (CAPD) and 38% with functioning transplants. The prevalence rate for dialysis was 68 per million population (p.m.p.) and that of transplant 42 p.m.p. The new dialysis acceptance rate was 15 p.m.p. and transplant 5 p.m.p. Forty-seven per cent of new patients had unknown primary renal disease and 30% was due to non-insulin dependent diabetes mellitus. Mean age of prevalent HD patients was 42 years, CAPD 46 years and 34 years for transplant. Patient survival on CAPD was 85% at 1 year and for HD was 88%. One year transplant patient survival was 94% and graft survival 91%.     

Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis

Endothelial dysfunction, including endothelial hyporesponsiveness to prototypical angiogenic growth factors and eNOS agonists, underlies vascular pathology in many dysmetabolic states. We investigated effects of a saturated free fatty acid, palmitic acid (PA), on endothelial cell responses to VEGF. PA-pretreated endothelial cells had markedly diminished Akt, eNOS, and ERK activation responses to VEGF, despite normal VEGFR2 phosphorylation. PA inhibited VEGF-induced angiogenic cord formation in Matrigel, and PA-treated endothelial cells accumulated early species (C16) ceramide. The serine palmitoyltransferase inhibitor myriocin reversed these defects. Protein phosphatase 2A (PP2A) became more eNOS-associated in PA-treated cells; the PP2A inhibitor okadaic acid reversed PA-induced signaling defects. Mice fed a diet high in saturated fat for 2 to 3 weeks had impaired i) aortic Akt and eNOS phosphorylation to infused VEGF, ii) ear angiogenic responses to intradermal adenoviral-VEGF injection, and iii) vascular flow recovery to hindlimb ischemia as indicated by laser Doppler and α_Vβ₃ SPECT imaging. High-fat feeding did not impair VEGF-induced signaling or angiogenic responses in mice with reduced serine palmitoyltransferase expression. Thus, de novo ceramide synthesis is required for these detrimental PA effects. The findings demonstrate an endothelial VEGF resistance mechanism conferred by PA, which comprises ceramide-induced, PP2A-mediated dephosphorylation of critical activation sites on enzymes central to vascular homeostasis and angiogenesis. This study defines potential molecular targets for preservation of endothelial function in metabolic syndrome.Endothelial dysfunction is the inability of the endothelium to promote vasodilation in a stimulus-dependent fashion, primarily as a consequence of impaired nitric oxide (NO) production. Individuals with risk factors for vascular disease, including metabolic syndrome and dysplipidemia,¹ exhibit varying degrees of endothelial dysfunction, which is an early feature of vascular pathology with prognostic significance.² Elevation of circulating free fatty acids (FFAs), experimentally or as seen in obese insulin-resistant individuals and in type 2 diabetes, results in 40% to 50% lower endothelium-dependent vasodilation.^3,4 The elevation of circulating FFA in obesity, metabolic syndrome, and type 2 diabetes is associated with impaired endothelium-dependent vasodilation, suggesting a link between FFA and endothelial dysfunction. We investigated such a link by assessing the effect of FFA on NO-producing growth factor signaling in the endothelium.Similar to hyperinsulinemia in insulin resistance, elevated systemic VEGF levels have been detected in individuals with visceral obesity, type 2 diabetes, and atherosclerosis.^5,6 VEGF levels are also elevated in chronically ischemic coronary and peripheral artery disease states,⁶ as well as in essential hypertension.⁷ In the present study, we evaluated the effects of palmitic acid (PA) on endothelial signaling responses to VEGF. PA profoundly impaired VEGF-dependent eNOS activation and angiogenic responses in vitro and in two independent in vivo murine models. The effects of PA were dependent on de novo synthesis of ceramide, which increased association of protein phosphatase 2A (PP2A) with eNOS. Here, we discuss this VEGF resistance as a possible central feature of the widespread vascular pathology seen in numerous dysmetabolic states.