Victor Chang Cardiac Research Institute

About: Victor Chang Cardiac Research Institute is a nonprofit organization based out in Sydney, New South Wales, Australia. It is known for research contribution in the topics: Mechanosensitive channels & Heart failure. The organization has 708 authors who have published 1599 publications receiving 70035 citations.

Probe-Directed Degradation (PDD) for Flexible Removal of Unwanted cDNA Sequences from RNA-Seq Libraries.

Abstract: Most applications for RNA-seq require the depletion of abundant transcripts to gain greater coverage of the underlying transcriptome. The sequences to be targeted for depletion depend on application and species and in many cases may not be supported by commercial depletion kits. This unit describes a method for generating RNA-seq libraries that incorporates probe-directed degradation (PDD), which can deplete any unwanted sequence set, with the low-bias split-adapter method of library generation (although many other library generation methods are in principle compatible). The overall strategy is suitable for applications requiring customized sequence depletion or where faithful representation of fragment ends and lack of sequence bias is paramount. We provide guidelines to rapidly design specific probes against the target sequence, and a detailed protocol for library generation using the split-adapter method including several strategies for streamlining the technique and reducing adapter dimer content.

Cardiovascular magnetic resonance imaging for structural heart disease.

Abstract: Cardiovascular magnetic resonance (CMR) has increasingly become a powerful imaging technique over the past few decades due to increasing knowledge about clinical applications, operator experience and technological advances, including the introduction of high field strength magnets, leading to improved signal-to-noise ratio. Its success is attributed to the free choice of imaging planes, the wide variety of imaging techniques, and the lack of harmful radiation. Developments in CMR have led to the accurate evaluation of cardiac structure, function and tissues characterisation, so this non-invasive technique has become a powerful tool for a broad range of cardiac pathologies. This review will provide an introduction of magnetic resonance imaging (MRI) physics, an overview of the current techniques and clinical application of CMR in structural heart disease, and illustrated examples of its use in clinical practice.

Permanent pacing for late-onset atrioventricular block in patients with heart transplantation: a single center experience.

Abstract: INTRODUCTION: The incidence, mechanisms, clinical associations, and outcomes in patients with late-onset (>3 months) atrioventricular (AV) block following heart transplantation are not well known. This study will characterize late-onset AV block following cardiac transplantation. METHODS: We retrospectively reviewed our databases to identify patients who required pacemakers for late-onset AV block postheart and heart-lung transplantation from January 1990 to December 2007. Orthotopic heart and heart-lung transplantation were separately analyzed. RESULTS: This study included 588 adults who received cardiac transplants over a 17-year period at our center (519 orthotopic, 64 heart-lung transplants, and five heterotopic heart transplants). Of the 519 patients with orthotopic heart transplant, 39 required pacing (7.5%), 17 (3.3%) within 3 months posttransplant, 11 (2.1%) for late-onset sinus node dysfunction (SND), 11 (2.1%) for late-onset AV block. Also, five patients (7.8%) out of 64 heart-lung transplants required pacemakers, two (3.1%) for late-onset SND, three (4.7%) for late-onset AV block. None of the five patients who underwent heterotopic transplant required cardiac pacing prior to or posttransplant. CONCLUSIONS: Late-onset AV block occurs in 2.4% of patients with orthotopic heart transplant or heart-lung transplant. AV block is predominantly intermittent and, often, does not progress to permanent AV block. There are no predictable factors for its onset.

Heightened α1A-adrenergic receptor activity suppresses ischaemia/reperfusion-induced Ins(1,4,5)P3 generation in the mouse heart : a comparison with ischaemic preconditioning

Abstract: Reperfusion of ischaemic rat or mouse hearts causes NE [noradrenaline (‘norepinephrine’)] release, stimulation of α1-ARs (α1-adrenergic receptors), PLC (phospholipase C) activation, Ins(1,4,5) P 3 generation and the development of arrhythmias. In the present study, we examined the effect of increased α1A-AR drive on these responses. In hearts from non-transgenic mice (α1A-WT), Ins(1,4,5) P 3 generation was observed after 2 min of reperfusion following 30 min of zero-flow ischaemia. No Ins(1,4,5) P 3 response was observed in hearts from transgenic mice with 66-fold overexpression of α1A-AR (α1A-TG). This was despite the fact that α1A-TG hearts had 8–10-fold higher PLC responses to NE than α1A-WT under normoxic conditions. The immediate phospholipid precursor of Ins(1,4,5) P 3, PtdIns(4,5) P 2, responded to ischaemia and reperfusion similarly in α1A-WT and α1A-TG mice. Thus the lack of Ins(1,4,5) P 3 generation in α1A-TG mice is not caused by limited availability of PtdIns(4,5) P 2. Overall, α1-AR-mediated PLC activity was markedly enhanced in α1A-WT mice under reperfusion conditions, but responses in α1A-TG mice were not significantly different in normoxia and post-ischaemic reperfusion. Ischaemic preconditioning prevented Ins(1,4,5) P 3 generation after 30 min of ischaemic insult in α1A-WT mice. However, the precursor lipid PtdIns(4,5) P 2 was also reduced by preconditioning, whereas heightened α1A-AR activity did not influence PtdIns(4,5) P 2 responses in reperfusion. Thus preconditioning and α1A-AR overexpression have different effects on early signalling responses, even though both prevented Ins(1,4,5) P 3 generation. These studies demonstrate a selective inhibitory action of heightened α1A-AR activity on immediate post-receptor signalling responses in early post-ischaemic reperfusion. Abbreviations: AR, adrenergic receptor; IP3-R, Ins(1,4,5)P3 receptor; NE, noradrenaline; PLC, phospholipase C; TCA, trichloroacetic acid; TG, transgenic; WT, wild-type

Conditional (loxP-flanked) allele for the gene encoding the retinoic acid-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2).

Abstract: Retinoic acid, the active vitamin A derivative, has pleiotropic functions during vertebrate development and postnatal life. Retinaldehyde dehydrogenase 2 (RALDH2) acts as the main retinoic acid-synthesizing enzyme during development. Mouse Raldh2 germline null mutants are early embryonic lethal and exhibit complex abnormalities that include defective heart looping morphogenesis. To investigate later functions of this enzyme, we have engineered a "floxed" (loxP-flanked) allele allowing Cre-mediated somatic gene inactivations. Mice heterozygous or homozygous for the floxed Raldh2 allele are viable and fertile. We tested whether the novel Raldh2 allele behaves as a null mutation after Cre-mediated in vivo excision by crossing the conditional mutants with CMV-Cre transgenic mice. An embryonic lethal phenotype indistinguishable from that of germline mutants was obtained. The conditional allele described herein is a genetic tool for studying tissue-specific, RALDH2-dependent functions of retinoic acid during development and in adult life.