Ryanodine receptor phosphorylation in human heart failure

Heart failure is a complex disorder, characterized by activation of the sympathetic nervous system, leading to dysregulated Ca2+ homeostasis in cardiac myocytes and tissue remodeling. In a variety of diseases, cardiac malfunction is associated with aberrant fluxes of Ca2+ across both the surface membrane and the internal Ca2+ store, the sarcoplasmic reticulum (SR). One prominent hypothesis residues is that in heart failure, the activity of the ryanodine receptor (RyR2) Ca2+ release channel in the SR is increased due to excess phosphorylation and that this contributes to excess SR Ca2+ leak in diastole, reduced SR Ca2+ load and decreased contractility (Huke & Bers, 2008). There is controversy over which serine residues in RyR2 are hyperphosphorylated in animal models of heart failure and whether this is via the CaMKII or the PKA-linked signaling pathway. S2808, S2814 and S2030 in RyR2 have been variously claimed to be hyperphosphorylated. Our aim was to examine the degree of phosphorylation of these residues in RyR2 from failing human hearts. The use of human tissue was approved by the Human Research Ethics Committee, The Prince Charles Hospital, EC28114. Left ventricular tissue samples were obtained from an explanted heart of a patient with endstage heart failure (Emery Dreifuss Muscular Dystrophy with cardiomyopathy) and non-failing tissue was from a patient with cystic fibrosis undergoing heart-lung transplantation with no history of heart disease. SR vesicles were prepared as described by Laver et al. (1995) and examined with SDS-Page and Western Blot. Transferred proteins were probed with antibodies to detect total protein phosphorylation, phosphorylation of RyR2 serine residues S2808, S2814, S2030 and for the key proteins calsequestrin, triadin, junctin and FKBP12.6. To avoid membrane stripping artifact, each membrane was exposed to one phosphorylation-specific antibody and signal densities quantified using Bio-Rad Quantity One software. We found no distinguishable difference between failing and healthy hearts in the protein expression levels of RyR2, triadin, junctin or calsequestrin. We found an expected upregulation of total RyR2 phosphorylation in the failing heart sample, compared to a matched amount of RyR2 (quantified using densiometry) in healthy heart. Probing with antibodies detecting only the phosphorylated form of the specific RyR2 residues showed that the increase in total RyR2 phosphorylation in the failing heart was due to hyperphosphorylation of S2808 and S2814. We found that S2030 phosphorylation levels were unchanged in human heart failure. Interestingly, we found that S2030 has a basal level of phosphorylation in the healthy human heart, different from the absence of basal phosphorylation recently reported in rodent heart (Huke & Bers, 2008). Finally, preliminary results indicate that less FKBP 12.6 is associated with RyR2 in the failing heart, possibly as a consequence of PKA activation. In conclusion, residues S2808 and S2814 are hyperphosphorylated in human heart failure, presumably due to upregulation of the CaMKII and/or PKA signaling pathway as a result of chronic activation of the sympathetic nervous system. Such changes in RyR2 phosphorylation are believed to contribute to the leaky RyR2 phenotype associated with heart failure, which increases the incidence of arrhythmia and contributes to the severely impaired contractile performance of the failing heart. Huke S & Bers DM. (2008). Ryanodine receptor phosphorylation at serine 2030, 2808 and 2814 in rat cardiomyocytes. Biochemical and Biophysical Research Communications 376, 80-85. Laver DR, Roden LD, Ahern GP, Eager KR, Junankar PR & Dulhunty AF. (1995). Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle. Journal of Membrane Biology 147, 7-22. Proceedings

Nurse-led telephone interventions for people with cardiac disease : A review of the research literature

Background: Nurse-led telephone follow-up offers a relatively inexpensive method of delivering education and support for assisting recovery in the early discharge period; however, its efficacy is yet to be determined. Aim: To perform a critical integrative review of the research literature addressing the effectiveness of nurse-led telephone interventions for people with coronary heart disease (CHD). Methods: A literature search of five health care databases; Sciencedirect, Cumulative Index to Nursing and Allied Health Literature, Pubmed, Proquest and Medline to identify journal articles between 1980 and 2009. People with cardiac disease were considered for inclusion in this review. The search yielded 128 papers, of which 24 met the inclusion criteria. Results: A total of 8330 participants from 24 studies were included in the final review. Seven studies demonstrated statistically significant differences in all outcomes measured, used two group experimental research design and valid and reliable instruments. Some positive effects were detected in eight studies in regards to nurse-led telephone interventions for people with cardiac disease and no differences were detected in nine studies. Discussion: Studies with some positive effects generally had stronger research designs, large samples, used valid and reliable instruments and extensive nurse-led educative interventions. Conclusion: The results suggest that people with cardiac disease showed some benefits from nurse-led/delivered telephone interventions. More rigorous research into this area is needed.

Development and pilot test of a peer-support based Cardiac-Diabetes Self-Management program : a study protocol

Background: People with cardiac disease and type 2 diabetes have higher hospital readmission rates (22%)compared to those without diabetes (6%). Self-management is an effective approach to achieve better health outcomes; however there is a lack of specifically designed programs for patients with these dual conditions. This project aims to extend the development and pilot test of a Cardiac-Diabetes Self-Management Program incorporating user-friendly technologies and the preparation of lay personnel to provide follow-up support. Methods/Design: A randomised controlled trial will be used to explore the feasibility and acceptability of the Cardiac-Diabetes Self-Management Program incorporating DVD case studies and trained peers to provide follow-up support by telephone and text-messaging. A total of 30 cardiac patients with type 2 diabetes will be randomised, either to the usual care group, or to the intervention group. Participants in the intervention group will received the Cardiac-Diabetes Self-Management Program in addition to their usual care. The intervention consists of three faceto- face sessions as well as telephone and text-messaging follow up. The face-to-face sessions will be provided by a trained Research Nurse, commencing in the Coronary Care Unit, and continuing after discharge by trained peers. Peers will follow up patients for up to one month after discharge using text messages and telephone support. Data collection will be conducted at baseline (Time 1) and at one month (Time 2). The primary outcomes include self-efficacy, self-care behaviour and knowledge, measured by well established reliable tools. Discussion: This paper presents the study protocol of a randomised controlled trial to pilot evaluates a Cardiac- Diabetes Self-Management program, and the feasibility of incorporating peers in the follow-ups. Results of this study will provide directions for using such mode in delivering a self-management program for patients with both cardiac condition and diabetes. Furthermore, it will provide valuable information of refinement of the intervention program.

Using user-friendly telecommunications to improve cardiac and diabetes self-management programme : a pilot study

Previous studies exploring the incidence and readmission rates of cardiac patients admitted to a coronary care unit (CCU) with type 2 diabetes [1] have been undertaken by the first author. Interviews of these patients regarding their experiences in managing their everyday conditions [2] provided the basis for developing the initial cardiac–diabetes self-management programme (CDSMP) [3]. Findings from each of these previous studies highlighted the complexity of self-management for patients with both conditions and contributed to the creation of a new self-management programme, the CDSMP, based on Bandura’s (2004) self-efficacy theory [4]. From patient and staff feedback received for the CDSMP [3], it became evident that further revision of the programme was needed to improve self-management levels of patients and possibility of incorporating methods of information technology (IT). Little is known about the applicability of different methods of technology for delivering self-management programmes for patients with chronic diseases such as those with type 2 diabetes and cardiac conditions. Although there is some evidence supporting the benefits and the great potential of using IT in supporting self-management programmes, it is not strong, and further research on the use of IT in such programmes is recommended [5–7]. Therefore, this study was designed to pilot test feasibility of the CDSMP incorporating telephone and text-messaging as follow-up approaches.

Cardiac health diagnosis using higher order spectra and support vector machine

The Electrocardiogram (ECG) is an important bio-signal representing the sum total of millions of cardiac cell depolarization potentials. It contains important insight into the state of health and nature of the disease afflicting the heart. Heart rate variability (HRV) refers to the regulation of the sinoatrial node, the natural pacemaker of the heart by the sympathetic and parasympathetic branches of the autonomic nervous system. The HRV signal can be used as a base signal to observe the heart's functioning. These signals are non-linear and non-stationary in nature. So, higher order spectral (HOS) analysis, which is more suitable for non-linear systems and is robust to noise, was used. An automated intelligent system for the identification of cardiac health is very useful in healthcare technology. In this work, we have extracted seven features from the heart rate signals using HOS and fed them to a support vector machine (SVM) for classification. Our performance evaluation protocol uses 330 subjects consisting of five different kinds of cardiac disease conditions. We demonstrate a sensitivity of 90% for the classifier with a specificity of 87.93%. Our system is ready to run on larger data sets.