The association between O2-pulse slope ratio and functional severity of coronary stenosis: A combined cardiopulmonary exercise testing and quantitative flow ratio study.

Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.

Amyloid-ß Oligomer-Induced Electrophysiological Mechanisms and Electrical Impedance Changes in Neurons.

Amyloid plays a critical role in the pathogenesis of Alzheimer's disease (AD) and can aggregate to form oligomers and fibrils in the brain. There is increasing evidence that highly toxic amyloid-ß oligomers (AßOs) lead to tau protein aggregation, hyperphosphorylation, neuroinflammation, neuronal loss, synaptic loss, and dysfunction. Although the effects of AßOs on neurons have been investigated using conventional biochemical experiments, there are no established criteria for electrical evaluation. To this end, we explored electrophysiological changes in mouse hippocampal neurons (HT22) following exposure to AßOs and/or naringenin (Nar, a flavonoid compound) using electrical impedance spectroscopy (EIS). AßO-induced HT22 showed a decreased impedance amplitude and increased phase angle, and the addition of Nar reversed these changes. The characteristic frequency was markedly increased with AßO exposure, which was also reversed by Nar. The AßOs decreased intranuclear and cytoplasmic resistance and increased nucleus resistance and extracellular capacitance. Overall, the innovative construction of the eight-element CPE-equivalent circuit model further reflects that the pseudo-capacitance of the cell membrane and cell nucleus was increased in the AßO-induced group. This study conclusively revealed that AßOs induce cytotoxic effects by disrupting the resistance characteristics of unit membranes. The results further support that EIS is an effective technique for evaluating AßO-induced neuronal damage and microscopic electrical distinctions in the sub-microscopic structure of reactive cells.

Oxygen pulse variation in symptomatic patients with suspected coronary artery disease: a diagnostic analysis.

Background: Cardiopulmonary exercise testing (CPET) has been found high sensitivity and specificity in cardiac ischemia. However, the role of CPET in coronary artery disease (CAD) is unclear. This study was to explore the diagnostic value of CPET indicators in CAD. Methods: A total of 138 symptomatic patients with suspected CAD who underwent a CPET were included in this cross-sectional study. CPET indicators of all individuals were collected. ΔVO2/HR(Peak-AT) defined as the difference between the value of the oxygen consumption/heart rate (VO2/HR) at anaerobic threshold and peak exercise. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score of all the CAD patients was calculated based on the complexity of the coronary lesions. The diagnostic performance of the CPET indicators was assessed by the area under the curve (AUC), sensitivity, and specificity. Results: No significant differences in the CPET indicators were observed among the patients with or without CAD. The high SNYTAX score (≥22) group showed a significant reduction in the ΔVO2/HR(Peak-AT) compared to the low SNYTX score (<22) group (P=0.004). The AUC of the ΔVO2/HR(Peak-AT) was 0.804 (P=0.005), with the sensitivity of 95.7% and the specificity of 62.5%. The other CPET indicators did not differ significantly between the 2 groups. Oxygen pulse variation after the anaerobic threshold (AT) is superior to other CPET-derived variables in detecting intermediate to severe stenosis of the coronary artery in CAD patients. Conclusions: The ΔVO2/HR(Peak-AT) is a quantitative indicator of the variation of the oxygen pulse response after the AT during incremental exercise. However, due to sample limitations, our results need to be interpreted with caution.

A Dendrite-Resistant Zinc-Air Battery.

Zinc-air batteries (ZABs) have drawn widespread attention for their high energy densities, abundant raw materials, and low cost. However, the issues of metal dendrite formation and air electrode failure have been impeding the development and application of ZABs. Herein, we designed a novel dendrite-resistant ZAB system by adopting multiphase electrolytes to conduct the zinc deposition and the oxygen evolution reaction. The oxygen reduction reaction electrode is kept out of the zinc deposition region to extend the lifespan. The ZABs show an energy density of 1,050.9 Wh kg-1 based on the mass of zinc consumption, with an average Coulombic efficiency of ∼97.4% in 2,000 h discharge and charge cycling. More impressively, even if a short circuit occurs while charging, the battery can maintain the cycle performance without irreversible failure, which is conducive to the reliability of battery modules and its application in other energy storage/conversion devices.

Ibutilide Reduces Ventricular Defibrillation Threshold and Organizes Ventricular Fibrillation Activation in Canine Heart Failure Model.

PURPOSE: To compare the effects of class III antiarrhythmic agents (amiodarone vs. ibutilide) on ventricular fibrillation (VF) and hemodynamic status in a canine heart failure (HF) model. METHODS: A total of 12 beagles were used to establish the HF model by rapid pacing for 4 consecutive weeks. These canines were randomly divided into two groups based on the administration of ibutilide and amiodarone. A 12 × 12 unipolar electrode plaque was used for ventricular epicardial mapping, and a 6-electrode plunge needle was inserted for ventricular transmural mapping. The restitution curve was estimated from activation recovery intervals (ARIs) by pacing from the plaque electrodes before and after drug administration. The defibrillation threshold (DFT) and VF activation patterns, including the activation rate, cycle length (VF-CL) and the transmural dispersion of the activation rate, were evaluated and the hemodynamic parameters were mearsured and compared before and after drug administration. RESULTS: Compared to HF baseline, ibutilide administration has markedly decreased the DFT by 28% (18 ± 2 J vs. 13 ± 2.7 J, P < 0.01) without affecting the canine's hemodynamics (mean arterial pressure 91 ± 15 mmHg vs. 92 ± 17 mmHg, P > 0.05). Furthermore, VF activation pattern became more organized, and spontaneous termination was observed only after ibutilide administration. Conversely, amiodarone has significantly compromised the hemodynamic status (mean arterial pressure 92 ± 6.1 mmHg vs. 52 ± 11.6 mmHg, P < 0.05), but did not alter the DFT (17 ± 2.3 J vs. 16 ± 2.0 J, P > 0.05). Compared to pre-medication, both ibutilide and amiodarone have significantly prolonged the VERP (178 ± 9.6 ms vs. 208 ± 8.9 ms, P < 0.05; 185 ± 10.5 ms vs. 202 ± 7.5 ms, P < 0.05, respectively) and reduced the dispersion of refractoriness, the maximal slope of restitution curve, and the epicardial dispersion during pacing. Additionally, both drugs have significantly increased the VF-CL and reduced the transmural dispersion of the VF activation rate. CONCLUSIONS: Ibutilide had potential antifibrillatory properties, which was shown by decreasing the DFT and organizing the VF activation in HF, and with no apparent impact on the hemodynamic status. In contrast, intravenous amiodarone administration demonstrated prominent negative effects on the hemodynamic status possibly by affecting the myocardial contractility before and after defibrillation but did not alter the DFT.

Impact of Pulmonary Vein Anatomy on Long-term Outcome of Cryoballoon Ablation for Atrial Fibrillation.

Variant pulmonary vein anatomy (PVA) has been reported to influence the recurrence of atrial fibrillation (AF) after radiofrequency ablation. However, the effects of PVA on AF in patients undergoing cryoballoon ablation (CBA) remain unknown. The present study aimed to examine the impact of PVA on the long-term outcome of CBA for AF. A total of 78 patients (mean age 60.7±10.9 years, 64.1% males) with symptomatic and drug-refractory paroxysmal AF were enrolled in the study. Left atrium (LA) and PVA acquired at computed tomography angiography (CTA) were reconstructed with CARTO® 3 SYSTEM. Patients were routinely evaluated by 24-hour Holter monitoring following CBA. Cox regression was used to detect the predictors of AF recurrence after CBA. The results showed abnormal PVA in 30 patients (38.5%) and 18 patients (23.1%) had left common PV (LCPV). Electrical pulmonary vein isolation was achieved in all patients. After a mean follow-up of 689.5±103.8 days, it was found that patients with abnormal PVA had similar AF recurrence rate to those with normal PVA (26.7% vs. 25.0%, P=0.54), and there was no significant difference in AF recurrence rate between LCPV patients and non-LCPV patients (33.7% vs. 23.3%, P=0.29). Cox regression analysis showed that AF duration (72.9±9.0 vs. 42.3±43.2 months, HR 1.001; 95%CI 1.003-1.014; P<0.001) and cryo-applications of right-side PVs (3.0±1.6 vs. 4.7±1.7, HR 0.661; 95% CI 0.473-0.925; P=0.016) were independent predictors of freedom from AF, but PVA was not identified as a predictor of long-term success. In conclusion, the variant PVA cannot significantly influence the long-term outcome of AF patients undergoing CBA; longer AF duration and less cryo-applications of right-side PVs are associated with higher AF recurrent rate.

Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

NEW FINDINGS: What is the central question of this study? In the present study, we investigated the effects of renal denervation on the vulnerability to ventricular fibrillation and the ventricular electrical properties in a rapid pacing-induced heart failure canine model. What is the main finding and its importance? Renal denervation significantly attenuated the process of heart failure and improved left ventricular systolic dysfunction, stabilized ventricular electrophysiological properties and decreased the vulnerability of the heart to ventricular fibrillation during heart failure. Thus, renal denervation can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action in a pacing-induced heart failure canine model. In this study, we investigated the effects of renal denervation (RDN) on the vulnerability to ventricular fibrillation (VF) and the ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). Heart failure was induced by rapid right ventricular pacing. Renal denervation was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle. The restitution properties and dispersion of refractoriness were estimated from the activation recovery intervals (ARIs) by a pacing protocol. The VF threshold (VFT) was defined as the maximal pacing cycle length required to induce VF using a specific pacing protocol. The defibrillation threshold (DFT) was measured by an up-down algorithm. Renal denervation partly restored left ventricular systolic function and attenuated the process of HF. Compared with the control group, the VFT in the HF group was decreased by 27% (106 ± 8.0 versus 135 ± 10 ms, P < 0.01). However, RDN increased the VFT by 13% (135 ± 10 versus 118 ± 7.5 ms, P < 0.05) and decreased the DFT by 27% (30 ± 6.3 versus 21.8 ± 4.7 J, P < 0.05) in the treated hearts compared with the failing hearts. Renal denervation significantly flattened the ventricular ARI restitution curve by 15% (1.48 ± 0.2 versus 1.26 ± 0.11, P < 0.05) and decreased the dispersion of ARI by 25% (0.08 ± 0.02 versus 0.06 ± 0.01, P < 0.01) in the treated group compared with the HF group. The findings of this study suggest that RDN can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action on VF in a canine model of pacing-induced HF.

Restitution characteristics of His bundle and working myocardium in isolated rabbit hearts.

The Purkinje system (PS) and the His bundle have been recently implicated as an important driver of the rapid activation rate after 1-2 minutes of ventricular fibrillation (VF). It is unknown whether activations during VF propagate through the His-Purkinje system to other portions of the the working myocardium (WM). Little is known about restitution characteristic differences between the His bundle and working myocardium at short cycle lengths. In this study, rabbit hearts (n = 9) were isolated, Langendorff-perfused, and electromechanically uncoupled with blebbistatin (10 µM). Pacing pulses were delivered directly to the His bundle. By using standard glass microelectrodes, action potentials duration (APD) from the His bundle and WM were obtained simultaneously over a wide range of stimulation cycle lengths (CL). The global F-test indicated that the two restitution curves of the His bundle and the WM are statistically significantly different (P<0.05). Also, the APD of the His bundle was significantly shorter than that of WM throughout the whole pacing course (P<0.001). The CL at which alternans developed in the His bundle vs. the WM were shorter for the His bundle (134.2±13.1ms vs. 148.3±13.3ms, P<0.01) and 2:1 block developed at a shorter CL in the His bundle than in WM (130.0±10.0 vs. 145.6±14.2ms, P<0.01). The His bundle APD was significantly shorter than that of WM under both slow and rapid pacing rates, which suggest that there may be an excitable gap during VF and that the His bundle may conduct wavefronts from one bundle branch to the other at short cycle lengths and during VF.

Global Bi-ventricular endocardial distribution of activation rate during long duration ventricular fibrillation in normal and heart failure canines.

BACKGROUND: The objective of this study was to detect differences in the distribution of the left and right ventricle (LV & RV) activation rate (AR) during short-duration ventricular fibrillation (SDVF, <1 min) and long-duration ventricular fibrillation VF (LDVF, >1 min) in normal and heart failure (HF) canine hearts. METHODS: Ventricular fibrillation (VF) was electrically induced in six healthy dogs (control group) and six dogs with right ventricular pacing-induced congestive HF (HF group). Two 64-electrode basket catheters deployed in the LV and RV were used for global endocardium electrical mapping. The AR of VF was estimated by fast Fourier transform analysis from each electrode. RESULTS: In the control group, the LV was activated faster than the RV in the first 20 s, after which there was no detectable difference in the AR between them. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the posterior LV was activated fastest, while the anterior was slowest. In the HF group, a detectable AR gradient existed between the two ventricles within 3 min of VF, with the LV activating more quickly than the RV. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of the LV was activated fastest, while the anterior was activated slowest. CONCLUSIONS: A global bi-ventricular endocardial AR gradient existed within the first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR gradient was always observed in both SDVF and LDVF in HF hearts. The findings of this study suggest that LDVF in HF hearts can be maintained differently from normal hearts, which accordingly should lead to the development of different management strategies for LDVF resuscitation.

[Factors associated with the efficacy of cardiac resynchronization therapy in patients with chronic heart failure].

OBJECTIVE: To observe the clinical effects of cardiac resynchronization therapy (CRT) in patients with chronic heart failure, and compare the clinical characteristics and outcome between responders and non-responders to define factors related to the efficacy of CRT. METHODS: We retrospectively analyzed the data of patients underwent CRT-P/D implantation from January 2006 to December 2012 in our Hospital. All patients received long-term follow-up including NYHA classification, left ventricular ejection fraction (LVEF) and left ventricular internal dimension at end diastole (LVIDd). RESULTS: A total of 204 patients were included (130 males, mean age (64.8 ± 11.9) years). The total response rate of CRT was 61.3%. Women, QRS duration ≥ 150 ms, and left bundle branch block (LBBB) were related with better response after CRT (all P < 0.05). Multivariate regression analysis showed that QRS duration was an independent determinant for CRT response. All-cause mortality rate was significantly lower in responder group than in non-responder group (P < 0.001). CONCLUSIONS: In patients with chronic heart failure, women, QRS duration ≥ 150 ms, and LBBB are related with better CRT response rate post CRT. QRS duration ≥ 150 ms is an independent predictor of CRT response, and positive response is associated with lower all-cause mortality in this patient cohort.

Protective effect of carnosine on subcortical ischemic vascular dementia in mice.

AIMS: Recently, we found carnosine protects against N-Methyl-D-Aspartate (NMDA) induced excitotoxicity through a histaminergic pathway. The aim of this study was to determine whether the carnosine-histidine-histamine pathway also played a protective role in subcortical ischemic vascular dementia (SIVD). METHODS: Adult male mice (C57BL/6 strain) were subjected to right unilateral common carotid arteries occlusion (rUCCAO) and treated with carnosine or histidine. Object recognition test, passive avoidance task, Morris water maze, and immunohistochemical analyses were performed after rUCCAO. RESULTS: We found that carnosine (200, 500 mg/kg) ameliorated white matter lesion and cognitive impairment evaluated by object recognition test, passive avoidance task, and Morris water maze test after rUCCAO in both wide-type mice and histidine decarboxylase knockout mice, which are lack of endogenous histamine. However, administration of histidine did not show the same effect. The myelin basic protein in the corpus callosum decreased obviously at day 37 after rUCCAO, which was largely reversed by carnosine (200, 500 mg/kg). Carnosine (200, 500 mg/kg) suppressed the activation of microglia and astrocyte as attenuating the elevation of glial fibrillary acidic protein (GFAP) and Iba-1 fluorescent intensity. Moreover, carnosine (200, 500 mg/kg) significantly attenuated the increase in reactive oxygen species generation after rUCCAO. CONCLUSION: These data suggest that the neuroprotective effect of carnosine on rUCCAO in mice is not dependent on the histaminergic pathway, but may be due to a suppression of reactive oxygen species generation, glia activation, and myelin degeneration.