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Yanyan Ma,1,* Ying Cao,2,* Hong Gao,3 Rui Tong,1 Jing Yi,3 Zhongwei Zhang,1 Rui Chen,1 Zhijun Pan1 1School of Anesthesia, Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Anesthesiology, The Second People’s Hospital of Guiyang, Guiyang, People’s Republic of China; 3Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Gao, Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, No. 9 Beijing Road, Guiyang, People’s Republic of China, Email 2169617@qq.com; anesth@qq.comPurpose: This study investigated the effect of exosomes derived from sevoflurane-treated cardiac fibroblasts (Sev-CFs-Exo) on reperfusion arrhythmias (RA), ventricular conduction, and myocardial ischemia-reperfusion injury (MIRI).Methods: Primary cardiac fibroblasts (CFs) were isolated from the hearts of neonatal rats and identified by morphology and immunofluorescence. Exosomes were isolated from CFs at passages 2– 3 after they had been treated with 2.5% sevoflurane for an hour and cultivated for 24– 48 hours. The control group was CFs that did not receive any treatment. The hypothermic global ischemia-reperfusion injury model was established using the Langendorff perfusion technique following injection with exosomes through the caudal vein. Multi-electrode array (MEA) mapping was used to investigate the changes in RA and ventricular conduction in isolated hearts. Western blots and immunofluorescence were used to examine the relative expression and location of connexin 43 (Cx43). In addition, the MIRI was evaluated with triphenyl tetrazolium chloride and Hematoxylin-Eosin staining.Results: The primary CFs had a variety of morphologies, no spontaneous pulsation, and were vimentin-positive, which confirmed their successful isolation. Sev-CFs-Exo increased the heart rate (HR) at reperfusion for 15 minutes (T2) and 30 minutes (T3) and lowered the score and duration of RA and the time for restoration of heartbeat in reperfusion. Meanwhile, Sev-CFs-Exo increased conduction velocity (CV), decreased absolute inhomogeneity (P5-95) and inhomogeneity index (P5-95/P50) at T2 and T3, as well as promoted the recovery of HR, CV, P5-95 and P5-95/P50 after hypothermic global ischemia-reperfusion injury. Furthermore, Sev-CFs-Exo raised expression and reduced lateralization of Cx43, and improved myocardial infarct sizes and cellular necrosis. However, while cardiac fibroblast-derived exosomes (CFs-Exo) showed similar cardioprotective effects, the outcomes were not as significant.Conclusion: Sevoflurane reduces the risk of RA and improves ventricular conduction and MIRI by CFs-Exo, and this may be driven by the expression and location of Cx43.Keywords: anesthetic, extracellular vesicles, arrhythmia, electrophysiology, electrical mapping, connexin 43, Cx43

Augmented reality (AR) has been found to be advantageous in enhancing visualization of complex neuroanatomy intraoperatively and in neurosurgical education. Another key tool that allows neurosurgeons to have enhanced visualization, namely of white matter tracts, is diffusion tensor imaging (DTI) that is processed with high-definition fiber tractography (HDFT). There remains an enduring challenge in the structural–functional correlation of white matter tracts that centers on the difficulty in clearly assigning function to any given fiber tract when evaluating them through separated as opposed to integrated modalities. Combining the technologies of AR with fiber tractography shows promise in helping to fill in this gap between structural–functional correlation of white matter tracts. This novel study demonstrates through a series of three cases of awake craniotomies for glioma resections a technique that allows the first and most direct evidence of fiber tract stimulation and assignment of function or deficit in vivo through the intraoperative, real-time fusion of electrical cortical stimulation, AR, and HDFT. This novel technique has qualitatively shown to be helpful in guiding intraoperative decision making on extent of resection of gliomas. Future studies could focus on larger, prospective cohorts of glioma patients who undergo this methodology and further correlate the post-operative imaging results to patient functional outcomes.

Abstract Background Cyclic motor patterns (CMP) are the predominant motor pattern in the distal colon, and are important in both health and disease. Their origin, mechanism and relation to bioelectrical slow-waves remain incompletely understood. During abdominal surgery, an increase in the CMP occurs in the distal colon. This study aimed to evaluate the feasibility of detecting propagating slow waves and spike waves in the distal human colon through intraoperative, high-resolution (HR), serosal electrical mapping. Methods HR electrical recordings were obtained from the distal colon using validated flexible PCB arrays (6 × 16 electrodes; 4 mm inter-electrode spacing; 2.4 cm2, 0.3 mm diameter) for up to 15 min. Passive unipolar signals were obtained and analysed. Results Eleven patients (33–71 years; 6 females) undergoing colorectal surgery under general anaesthesia (4 with epidurals) were recruited. After artefact removal and comprehensive manual and automated analytics, events consistent with regular propagating activity between 2 and 6 cpm were not identified in any patient. Intermittent clusters of spike-like activities lasting 10–180 s with frequencies of each cluster ranging between 24 and 42 cpm, and an average amplitude of 0.54 ± 0.37 mV were recorded. Conclusions Intraoperative colonic serosal mapping in humans is feasible, but unlike in the stomach and small bowel, revealed no regular propagating electrical activity. Although sporadic, synchronous spike-wave events were identifiable. Alternative techniques are required to characterise the mechanisms underlying the hyperactive CMP observed in the intra- and post-operative period. New findings The aim of this study was to assess the feasibility of detecting propagating electrical activity that may correlate to the cyclic motor pattern in the distal human colon through intraoperative, high-resolution, serosal electrical mapping. High-resolution electrical mapping of the human colon revealed no regular propagating activity, but does reveal sporadic spike-wave events. These findings indicate that further research into appropriate techniques is required to identify the mechanism of hyperactive cyclic motor pattern observed in the intra- and post-operative period in humans.

Background: Second-generation cryoballoon ablation is safe and effective in patients with paroxysmal (PAF) and persistent atrial fibrillation (AF). Objective: This study aimed to assess the long-term clinical outcomes and freedom from AF in patients undergoing thermal-guided cryoablation without the use of an electrical mapping catheter. Methods: All patients who had undergone thermal-guided second-generation cryoablation without electrical mapping between January 2015 and April 2018 at Eastbourne District General Hospital were retrospectively analysed. Success was defined as freedom from atrial arrhythmia lasting >30 s during the follow up period. Results: The study included 234 patients with a mean age of 65.3 ± 10.6 years. There were 134 (57.0%) and 100 (42.7%) patients who had PAF and persistent AF respectively.Arrhythmia recurrence occurred in 38 of 134 (28.4%) PAF and 42 of 100 (42.0%) persistent AF patients after mean follow up of 40 ± 9.2 months. The patients with PAF had a significantly greater freedom from arrhythmia than patients with persistent AF (p = .040). The mean procedure time was 55.5 ± 12.2 min and the mean fluoroscopy time was 10.9 ± 4.8 min 73.5% of patients were discharged on the same day. Conclusion: Thermal-guided cryoablation is feasible, safe and results in freedom from arrhythmia in the majority of paroxysmal and persistent AF patients in the long term. Randomised controlled trials are required to confirm the findings of this study.

Background: Multisite pacing strategies that improve response to cardiac resynchronization therapy (CRT) have been proposed. Current available options are pacing 2 electrodes in a multipolar lead in a single vein (multipoint pacing [MPP]) and pacing using 2 leads in separate veins (multizone pacing [MZP]). Objective: The purpose of this study was to compare in a systematic manner the acute hemodynamic response (AHR) and electrophysiological effects of MPP and MZP and compare them with conventional biventricular pacing (BiVP). Methods: Hemodynamic and electrophysiological effects were evaluated in a porcine model of acute left bundle branch block (LBBB) (n = 8). AHR was assessed as LVdP/dtmax. Activation times were measured using >100 electrodes around the epicardium, measuring total activation time (TAT) and left ventricular activation time (LVAT). Results: Compared to LBBB, BiVP, MZP, and MPP reduced TAT by 26% ± 10%, 32% ± 13%, and 32% ± 14%, respectively (P = NS between modes) and LVAT by 4% ± 5%, 11% ± 5%, and 12% ± 5%, respectively (P 5 cm vs

Abstract Background Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration where a biventricular pacemaker is implanted to achieve faster activation and more synchronous contraction of the left ventricle (LV). Despite the convincing effect of CRT, 30–40% of patients do not respond. Among the most important correctable causes of non-response to CRT is non-optimal LV lead position. Methods We will enroll 122 patients in this patient-blinded and assessor-blinded, randomized, clinical trial aiming to investigate if implanting the LV lead guided by electrical mapping towards the latest LV activation as compared with imaging-guided implantation, causes an excess increase in left ventricular (LV) ejection fraction (LVEF). The patients are randomly assigned to either the intervention group: preceded by cardiac computed tomography of the cardiac venous anatomy, the LV lead is placed according to the latest LV activation in the coronary sinus (CS) branches identified by systematic electrical mapping of the CS at implantation and post-implant optimization of the interventricular pacing delay; or patients are assigned to the control group: placement of the LV lead guided by cardiac imaging. The LV lead is targeted towards the latest mechanical LV activation as identified by echocardiography and outside myocardial scar as identified by myocardial perfusion (MP) imaging. The primary endpoint is change in LVEF at 6-month follow up (6MFU) as compared with baseline measured by two-dimensional echocardiography. Secondary endpoints include relative percentage reduction in LV end-systolic volume, all-cause mortality, hospitalization for heart failure, and a clinical combined endpoint of response to CRT at 6MFU defined as the patient being alive, not hospitalized for heart failure, and experiencing improvement in NYHA functional class or/and > 10% increase in 6-minute walk test. Discussion We assume an absolute increase in LVEF of 12% in the intervention group versus 8% in the control group. If an excess increase in LVEF can be achieved by LV lead implantation guided by electrical mapping, this study supports the conduct of larger trials investigating the impact of this strategy for LV-lead implantation on clinical outcomes in patients treated with CRT. Trial registration ClinicalTrials.gov, NCT02346097. Registered on 12 January 2015. Patients were enrolled between 16 February 2015 and 13 December 2017.

Background: Cardiomyocyte progenitor cells (CMPCs) are a promising cell source for regenerative cell therapy to improve cardiac function after myocardial infarction. However, it is unknown whether undifferentiated CMPCs have arrhythmogenic risks. We investigate whether undifferentiated, regionally applied, human fetal CMPCs form a pro-arrhythmic substrate in co-culture with neonatal rat ventricular myocytes (NRVMs).Method: Unipolar extracellular electrograms, derived from micro-electrode arrays (8 × 8 electrodes) containing monolayers of NRVMs (control), or co-cultures of NRVMs and locally seeded CMPCs were used to determine conduction velocity and the incidence of tachy-arrhythmias. Micro-electrodes were used to record action potentials. Conditioned medium (Cme) of CMPCs was used to distinguish between coupling or paracrine effects.Results: Co-cultures demonstrated conduction slowing (5.6 ± 0.3 cm/s, n = 50) compared to control monolayers (13.4 ± 0.4 cm/s, n = 26) and monolayers subjected to Cme (13.7 ± 0.6 cm/s, n = 11, all p < 0.001). Furthermore, co-cultures had a more depolarized resting membrane than control monolayers (−47.3 ± 17.4 vs. −64.8 ± 7.7 mV, p < 0.001) and monolayers subjected to Cme (−64.4 ± 8.1 mV, p < 0.001). Upstroke velocity was significantly decreased in co-cultures and action potential duration was prolonged. The CMPC region was characterized by local ST-elevation in the recorded electrograms. The spontaneous rhythm was faster and tachy-arrhythmias occurred more often in co-cultured monolayers than in control monolayers (42.0 vs. 5.4%, p < 0.001).Conclusion: CMPCs form a pro-arrhythmic substrate when co-cultured with neonatal cardiomyocytes. Electrical coupling between both cell types leads to current flow between a, slowly conducting, depolarized and the normal region leading to local ST-elevations and the occurrence of tachy-arrhythmias originating from the non-depolarized zone.