88723 0 5 DOI:10.1016/j.redox.2013.10.010 http://api.elsevier.com.ucc.idm.oclc.org/content/article/doi/10.1016/j.redox.2013.10.010 Aging-dependent changes in rat heart mitochondrial glutaredoxins—Implications for redox regulation Xing-Huang, Gao AbstractClinical and animal studies have documented that hearts of the elderly are more susceptible to ischemia/reperfusion damage compared to young adults. Recently we found that aging-dependent increase in susceptibility of cardiomyocytes to apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1) and concomitant decrease in NF-κB-mediated expression of anti-apoptotic proteins. Besides primary localization in the cytosol, Grx1 also exists in the mitochondrial intermembrane space (IMS). In contrast, Grx2 is confined to the mitochondrial matrix. Here we report that Grx1 is decreased by 50–60% in the IMS, but Grx2 is increased by 1.4–2.6 fold in the matrix of heart mitochondria from elderly rats. Determination of in situ activities of the Grx isozymes from both subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria revealed that Grx1 was fully active in the IMS. However, Grx2 was mostly in an inactive form in the matrix, consistent with reversible sequestration of the active-site cysteines of two Grx2 molecules in complex with an iron–sulfur cluster. Our quantitative evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric Grx2 complex with iron–sulfur clusters are increased in SSM and IFM in the hearts of elderly rats. We found that the inactive Grx2 can be fully reactivated by sodium dithionite or exogenous superoxide production mediated by xanthine oxidase. However, treatment with rotenone, which generates intramitochondrial superoxide through inhibition of mitochondrial respiratory chain Complex I, did not lead to Grx2 activation. These findings suggest that insufficient ROS accumulates in the vicinity of dimeric Grx2 to activate it in situ. Redox Biology 22132317 1 1 2013-01-01 2013-12-31 2013 586 598 10.1016/j.redox.2013.10.010 1 true Journal Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved. S2213-2317(13)00079-7 Xing-Huang, Gao | Suparna, Qanungo | Harish V., Pai | David W., Starke | Kelly M., Steller | Hisashi, Fujioka | Edward J., Lesnefsky | Janos, Kerner | Mariana G., Rosca | Charles L., Hoppel | John J., Mieyal Aging | Glutaredoxin | Glutathionylation | Iron–sulfur cluster | Mitochondria | Reactive oxygen species (ROS) | Redox regulation DOI:10.1016/j.ahj.2013.08.018 http://api.elsevier.com.ucc.idm.oclc.org/content/article/doi/10.1016/j.ahj.2013.08.018 Diagnostic performance of non–contrast-enhanced whole-heart magnetic resonance coronary angiography in combination with adenosine stress perfusion cardiac magnetic resonance imaging Tobias, Heer BackgroundWe sought to evaluate the diagnostic performance of 1.5-T non-contrast enhanced whole-heart magnetic resonance coronary angiography (MRCA) alone and in combination with adenosine stress cardiac magnetic resonance imaging (CMR-Perf). MRCA has been proposed to allow for detection of coronary artery disease (CAD). Yet, recent studies failed to show an incremental value of MRCA when added to CMR-Perf.MethodsNon-Gadolinium 1.5-T contrast-enhanced, electrocardiogram-triggered, navigator-gated free-breathing MRCA was performed in 144 patients (pts) with suspected or known CAD. Accuracy of MRCA in detecting CAD was evaluated using X-ray coronary angiography as the reference. A novel algorithm was used to combine the results of MRCA and CMR-Perf.ResultsMRCA was diagnostic in 96/144 pts (67%) with regular breathing (mean age 62.5 ± 13); 77% of all coronary segments (939/1226) and 92% of segments suitable for percutaneous coronary intervention (792/866) were assessable. In 59 pts a novel algorithm to combine MRCA and CMR-Perf was performed with high diagnostic performance: accuracy, sensitivity, specificity, negative and positive predictive values were 91.5% (54/59; 95% CI, 84%-99%), 95.7% (22/23; 77-100), 88.9% (32/36; 74-96), 84.6% (22/26; 71-99), and 97.0% (32/33; 91-100). Compared to the combined use of CMR-Perf and late gadolinium enhancement, specificity with the novel algorithm significantly increased (P = .008).ConclusionMRCA has a high assessability in segments suitable for percutaneous coronary intervention in pts with regular breathing. The combined use of MRCA and CMR-Perf improved specificity for the detection of significant CAD. American Heart Journal 00028703 166 6 2013-12-01 2013-12-31 December 2013 999 1009 10.1016/j.ahj.2013.08.018 1 true Journal Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved. Clinical InvestigationImaging and Diagnostic Testing S0002-8703(13)00589-9 Tobias, Heer | Stephanie, Reiter | Berthold, Höfling | Günter, Pilz 84884511729 2-s2.0-84884511729 DOI:10.1016/j.yjmcc.2013.02.001 http://api.elsevier.com.ucc.idm.oclc.org/content/article/doi/10.1016/j.yjmcc.2013.02.001 Selective heart rate reduction with ivabradine slows ischaemia-induced electrophysiological changes and reduces ischaemia–reperfusion-induced ventricular arrhythmias Fu Siong, Ng AbstractHeart rates during ischaemia and reperfusion are possible determinants of reperfusion arrhythmias. We used ivabradine, a selective If current inhibitor, to assess the effects of heart rate reduction (HRR) during ischaemia–reperfusion on reperfusion ventricular arrhythmias and assessed potential anti-arrhythmic mechanisms by optical mapping. Five groups of rat hearts were subjected to regional ischaemia by left anterior descending artery occlusion for 8min followed by 10min of reperfusion: (1) Control n=10; (2) 1μM of ivabradine perfusion n=10; (3) 1μM of ivabradine+5Hz atrial pacing throughout ischaemia–reperfusion n=5; (4) 1μM of ivabradine+5Hz pacing only at reperfusion; (5) 100μM of ivabradine was used as a 1ml bolus upon reperfusion. For optical mapping, 10 hearts (ivabradine n=5; 5Hz pacing n=5) were subjected to global ischaemia whilst transmembrane voltage transients were recorded. Epicardial activation was mapped, and the rate of development of ischaemia-induced electrophysiological changes was assessed. HRR observed in the ivabradine group during both ischaemia (195±11bpm vs. control 272±14bpm, p<0.05) and at reperfusion (168±13bpm vs. 276±14bpm, p<0.05) was associated with reduced reperfusion ventricular fibrillation (VF) incidence (20% vs. 90%, p<0.05). Pacing throughout ischaemia–reperfusion abolished the protective effects of ivabradine (100% VF), whereas pacing at reperfusion only partially attenuated this effect (40% VF). Ivabradine, given as a bolus at reperfusion, did not significantly affect VF incidence (80% VF). Optical mapping experiments showed a delay to ischaemia-induced conduction slowing (time to 50% conduction slowing: 10.2±1.3min vs. 5.1±0.7min, p<0.05) and to loss of electrical excitability in ivabradine-perfused hearts (27.7±4.3min vs. 14.5±0.6min, p<0.05). Ivabradine administered throughout ischaemia and reperfusion reduced reperfusion VF incidence through HRR. Heart rate during ischaemia is a major determinant of reperfusion arrhythmias. Heart rate at reperfusion alone was not a determinant of reperfusion VF, as neither a bolus of ivabradine nor pacing immediately prior to reperfusion significantly altered reperfusion VF incidence. This anti-arrhythmic effect of heart rate reduction during ischaemia may reflect slower development of ischaemia-induced electrophysiological changes. Journal of Molecular and Cellular Cardiology 00222828 0 2013-06-01 2013-06-30 June 2013 67 75 10.1016/j.yjmcc.2013.02.001 1 true Journal Copyright © 2013 Elsevier Ltd. All rights reserved. Original article S0022-2828(13)00056-4 Fu Siong, Ng | Iqbal T., Shadi | Nicholas S., Peters | Alexander R., Lyon Ischaemia–reperfusion | Reperfusion arrhythmias | Ventricular arrhythmias | Ivabradine | Heart rate reduction 84874944254 2-s2.0-84874944254 23402927 DOI:10.1016/j.yjmcc.2013.09.014 http://api.elsevier.com.ucc.idm.oclc.org/content/article/doi/10.1016/j.yjmcc.2013.09.014 Myocardial glycophagy — A specific glycogen handling response to metabolic stress is accentuated in the female heart M.E., Reichelt AbstractCardiac metabolic stress is a hallmark of many cardiac pathologies, including diabetes. Cardiac glycogen mis-handling is a frequent manifestation of various cardiopathologies. Diabetic females have a higher risk of heart disease than males, yet sex disparities in cardiac metabolic stress settings are not well understood. Oestrogen acts on key glycogen regulatory proteins. The goal of this study was to evaluate sex-specific metabolic stress-triggered cardiac glycogen handling responses. Male and female adult C57Bl/6J mice were fasted for 48h. Cardiac glycogen content, particle size, regulatory enzymes, signalling intermediates and autophagic processes were evaluated. Female hearts exhibited 51% lower basal glycogen content than males associated with lower AMP-activated-kinase (AMPK) activity (35% decrease in pAMPK:AMPK). With fasting, glycogen accumulated in female hearts linked with decreased particle size and upregulation of Akt and AMPK signalling, activation of glycogen synthase and inactivation of glycogen phosphorylase. Fasting did not alter glycogen content or regulatory proteins in male hearts. Expression of glycogen autophagy marker, starch-binding-protein-domain-1 (STBD1), was 63% lower in female hearts than males and increased by 69% with fasting in females only. Macro-autophagy markers, p62 and LC3BII:I ratio, increased with fasting in male and female hearts. This study identifies glycogen autophagy (‘glycophagy’) as a potentially important component of the response to cardiac metabolic stress. Glycogen autophagy occurs in association with a marked and selective accumulation of glycogen in the female myocardium. Our findings suggest that sex-specific differences in glycogen handling may have cardiopathologic consequences in various settings, including diabetic cardiomyopathy. Journal of Molecular and Cellular Cardiology 00222828 0 2013-12-01 2013-12-31 December 2013 67 75 10.1016/j.yjmcc.2013.09.014 1 true Journal Copyright © 2013 The Authors. Published by Elsevier Ltd. All rights reserved. Original article S0022-2828(13)00277-0 M.E., Reichelt | K.M., Mellor | C.L., Curl | D., Stapleton | L.M.D., Delbridge Cardiac | Gender | Sex | Fasting | Autophagy 84885543075 2-s2.0-84885543075 DOI:10.1016/j.ehj.2013.08.010 http://api.elsevier.com.ucc.idm.oclc.org/content/article/doi/10.1016/j.ehj.2013.08.010 Right ventricular systolic echocardiographic parameters in chronic systolic heart failure and prognosis Khaled E., Darahim AbstractBackgroundRight ventricular (RV) dysfunction is associated with poor prognosis in patients with heart failure (HF). Several RV echocardiographic parameters have been proposed as sensitive markers to detect patients at risk.ObjectiveThe aim is to compare the predictive value of several RV systolic echocardiographic parameters for adverse outcome in patients with chronic systolic HF.MethodsWe assessed 117 patients with chronic systolic HF and left ventricular ejection fraction (LVEF) <40% for the following: (i) RV fractional area change (RVFAC), (ii) tricuspid annular plane systolic excursion (TAPSE), (iii) integral of the systolic wave (ISWtdi), and (iv) peak systolic velocity (Satdi). ISWtdi and Satdi were measured using tissue Doppler imaging at the tricuspid annulus. The primary endpoint was death, urgent transplantation, or acute HF episode requiring hospital admission. The follow-up extended for one year.ResultsFifty-two patients reached the primary endpoint. The cut-off thresholds for RVFAC, TAPSE, Satdi, and ISWtdi defined using receiver-operating characteristic curves were 30%, 15.5mm, 10.0cm/s, and 2.4cm, respectively. The area under the curve and the 95% confidence interval for RVFAC, TAPSE, Satdi, and ISWtdi were 0.71(0.65–0.85), 0.66(0.55–0.76), 0.85(0.70–0.96), and 0.75(0.64–0.86), respectively. NYHA>2, and Satdi were found to be independent predictors of adverse outcome.ConclusionSatdi is an independent predictor of adverse outcome in HF at a threshold value of 10.0cm/s and appears to be superior to other RV systolic echocardiographic parameters. The Egyptian Heart Journal 11102608 0 2013-10-13 Available online 13 October 2013 10.1016/j.ehj.2013.08.010 1 true Journal Copyright © 2013 Production and hosting by Elsevier B.V. Invited Article S1110-2608(13)00086-0 Khaled E., Darahim Heart failure | Right ventricle | Prognosis | Echocardiography