Abstract 193: Intraosseous Transfusion With Liposome-Encapsulated Hemoglobin (HbV) Comparably Improves Rat Survival and its Arrythmogenesis Undergoing Progressive Lethal 85% Hemorrhage With Central Venous Infusion: Possible Implication for Pre-Hospital Settings

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Bonpei Takase ◽  
Yuko Higashimura
Keyword(s):  
Blood Loss ◽  
Action Potential Duration ◽  
Electrophysiological Study ◽  
Blood Substitute ◽  
Prolonged Action ◽  
Central Venous ◽  
Blood Exchange ◽  
Mapping Analysis ◽  
Venous Infusion ◽  
Prolonged Action Potential Duration

Liposome-encapsulated hemoglobin (HbV) can serve as blood substitute in hemorrhagic shock (HS). To investigate the resuscitation effect of HbV through intraosseous transfusion (IO) on lethal hemorrhage and its efficacy on myocardial arrhythmogenesis, optical mapping analysis (OMP) and electrophysiological study (EPS) were performed in graded blood exchange up to 85% blood loss in rats. And it was compared with central venous infusion (CVI). Total 90 rats were randomly allocated into 6 subgroups as followings; through IO or CVI, gradually exchanged blood with 5% albumin (Alb-IO/CVI-groups), exchanged with washed rat erythrocyte (wRBC-IO/CVI-groups) and with HbV (HbV-IO/CVI-groups). Survival effects were examined in each six rat groups. After excising the heart, OMP and EPS were performed. All rats died in Alb-IO/CVI-groups whereas excellent and comparably survived for following >48-hours in wRBC-IO/CVI-groups and HbV-IO/CVI-groups (Figure 1). OMP revealed impaired (prolonged) action potential duration (APD) dispersion in LV in Alb-IO/CVI-groups. In contrast, myocardial APD dispersions in LV were substantially attenuated in HbV-IO/CVI-groups and wRBC-IO/CVI-groups (Figure 2). Lethal arrhythmias (VT/VF) were provoked by EPS in Alb-IO/CVI-groups. No VT/VF was induced in both HbV-IO/CVI-groups and wRBC-IO/CVI-groups. Conclusions: IO vascular access could a reliable bridging method to resuscitate lethal HS by HbV. This suggests that IO with HbV resuscitation might be useful in pre-hospital settings in HS through preventing lethal arrhythmias.

Abstract 117: Chronic Efficacy of Liposome-Encapsulated Hemoglobin (HbV) on Rat’s Lethal 85% Hemorrhage: Intraosseus HbV Transfusion Acutely Rescues Through Anti-Arrhythmogenic Effects on Myocardium That Continues in Chronic Phase

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Bonpei Takase ◽  
Yuko Higashimura ◽  
Kenichi Hashimoto
Keyword(s):  
Left Ventricle ◽  
Electrophysiological Study ◽  
Chronic Phase ◽  
Blood Substitute ◽  
Prolonged Action ◽  
Rat Erythrocytes ◽  
Mapping Analysis ◽  
Group Survival ◽  
Prolonged Action Potential Duration ◽  
Arrhythmogenic Effects

Introduction: Liposome-encapsulated hemoglobin vesicles (HbVs) can serve as a blood substitute with human blood. Method: To investigate the resuscitation effect of HbVs on lethal hemorrhage and their efficacy for decreasing myocardial arrhythmogenesis, optical mapping analysis (OMP) and an electrophysiological study (EPS) were performed in graded 85% hemorrhage in rats in both acute and chronic phase. Six rats were resuscitated by intraosseous infusion of 5% albumin solution (ALB group), while 6 rats by washed rat erythrocytes (wRBC group) and 6 rats by HbVs (HbV group). Survival effects over 24 hours were examined in > 10 rats in each group. After excising the heart, OMP and an EPS were performed. Results: All rats died in ALB group, whereas all survived subsequent 24 hours in wRBC group and HbV group. In acute phase, OMP showed impaired (prolonged) action potential duration dispersion (APDd) in left ventricle in ALB group. In contrast, myocardial APDds in left ventricle were substantially attenuated in HbV group and wRBC group. Lethal arrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF], VT/VF) were provoked by EPS in ALB group. No VT/VF was induced in both wRBC group and HbV group. In chronic phase of two weeks after the resuscitation, OMP and an EPS were performed again in excising the heart. Anti-arrhythmic effects were confirmed by normal OMP findings (Normal APDd) and No VT/VF induced as shown in Figure. Conclusions: Lethal hemorrhage causes VT/VF in the presence of impaired APDd. Intraosseous HbVs infusion acutely rescues lethal hemorrhage through preventing lethal arrhythmias with preserved APDd. These effects were preserved in chronic phase.

Method for isolation of human ventricular myocytes from single endocardial and epicardial biopsies

1995 ◽  
Vol 268 (4) ◽  
pp. H1757-H1764 ◽  
Author(s):  
G. A. Peeters ◽  
M. C. Sanguinetti ◽  
Y. Eki ◽  
H. Konarzewska ◽  
D. G. Renlund ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Electrophysiological Study ◽  
Prolonged Action ◽  
Adult Human ◽  
Biopsy Specimens ◽  
Ventricular Cells ◽  
Normal Human ◽  
Prolonged Action Potential Duration

The study of adult human ventricular cells has been limited by tissue availability. In this study we describe techniques for the isolation of Ca(2+)-tolerant adult human ventricular cells from both transvenous endomyocardial and epicardial biopsies. Ca(2+)-tolerant cells were obtained from 80% of the biopsies processed. Although the yield of Ca(2+)-tolerant myocytes from either type of biopsy was low (1–5%), myocytes with normal resting potentials and action potentials can be obtained from single biopsy specimens, providing a source of normal human myocytes for electrophysiological study. Resting potentials (Vrest) were recorded in 41 isolated right ventricular endomyocardial cells at 37 degrees C. Sixteen cells were depolarized (Vrest = -26 +/- 13 mV), and 25 cells had normal resting potentials (Vrest = -84 +/- 6 mV). Action potentials were recorded in 16 cells. At a pacing cycle length of 1 s, 4 cells had prolonged action potential duration at 90% (APD90, 718 +/- 26 ms) and 10 cells had normal APD90 (381 +/- 94 ms) compared with those recorded from intact right ventricular septal trabeculae from explanted hearts. Voltage-clamp studies of isolated human ventricular myocytes obtained from these biopsies document the presence of currents previously reported from cells isolated from explanted hearts.

scholarly journals Human Cardiac Mesenchymal Stem Cells Remodel in Disease and Can Regulate Arrhythmia Substrates

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Prasongchai Sattayaprasert ◽  
Sunil K. Vasireddi ◽  
Emre Bektik ◽  
Oju Jeon ◽  
Mohammad Hajjiri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Action Potential ◽  
Induced Pluripotent Stem Cells ◽  
Cardiac Myocytes ◽  
Pluripotent Stem Cells ◽  
Action Potential Duration ◽  
Calcium Release ◽  
Prolonged Action ◽  
Induced Pluripotent ◽  
Prolonged Action Potential Duration

Background: The mesenchymal stem cell (MSC), known to remodel in disease and have an extensive secretome, has recently been isolated from the human heart. However, the effects of normal and diseased cardiac MSCs on myocyte electrophysiology remain unclear. We hypothesize that in disease the inflammatory secretome of cardiac human MSCs (hMSCs) remodels and can regulate arrhythmia substrates. Methods: hMSCs were isolated from patients with or without heart failure from tissue attached to extracted device leads and from samples taken from explanted/donor hearts. Failing hMSCs or nonfailing hMSCs were cocultured with normal human cardiac myocytes derived from induced pluripotent stem cells. Using fluorescent indicators, action potential duration, Ca2+ alternans, and spontaneous calcium release (SCR) incidence were determined. Results: Failing and nonfailing hMSCs from both sources exhibited similar trilineage differentiation potential and cell surface marker expression as bone marrow hMSCs. Compared with nonfailing hMSCs, failing hMSCs prolonged action potential duration by 24% ( P <0.001, n=15), increased Ca2+ alternans by 300% ( P <0.001, n=18), and promoted spontaneous calcium release activity (n=14, P <0.013) in human cardiac myocytes derived from induced pluripotent stem cells. Failing hMSCs exhibited increased secretion of inflammatory cytokines IL (interleukin)-1β (98%, P <0.0001) and IL-6 (460%, P <0.02) compared with nonfailing hMSCs. IL-1β or IL-6 in the absence of hMSCs prolonged action potential duration but only IL-6 increased Ca2+ alternans and promoted spontaneous calcium release activity in human cardiac myocytes derived from induced pluripotent stem cells, replicating the effects of failing hMSCs. In contrast, nonfailing hMSCs prevented Ca2+ alternans in human cardiac myocytes derived from induced pluripotent stem cells during oxidative stress. Finally, nonfailing hMSCs exhibited >25× higher secretion of IGF (insulin-like growth factor)-1 compared with failing hMSCs. Importantly, IGF-1 supplementation or anti–IL-6 treatment rescued the arrhythmia substrates induced by failing hMSCs. Conclusions: We identified device leads as a novel source of cardiac hMSCs. Our findings show that cardiac hMSCs can regulate arrhythmia substrates by remodeling their secretome in disease. Importantly, therapy inhibiting (anti–IL-6) or mimicking (IGF-1) the cardiac hMSC secretome can rescue arrhythmia substrates.

scholarly journals Comparative Analysis of Genetic Variations in the Nav1.5 Sodium Channel Subunits that Underlie Brugada Syndrome Using Patient-Specific iPSC-CMs

2020 ◽  
Author(s):  
Yue Zhu ◽  
Linlin Wang ◽  
Chang Cui ◽  
Shaojie Chen ◽  
Hongwu Chen ◽  
...  
Keyword(s):  
Action Potential ◽  
Brugada Syndrome ◽  
Action Potential Duration ◽  
Sodium Current ◽  
Genetic Variations ◽  
Patient Specific ◽  
Control Group ◽  
Prolonged Action ◽  
Ips Cell ◽  
Prolonged Action Potential Duration

Abstract Background: Brugada syndrome (BrS) is an autosomal dominant disorder that causes a high predisposition to sudden cardiac death. Several genes have been reported to be associated with BrS. Considering that the heterogeneity in clinical manifestations may result from genetic variations, the application of patient-specific induced pluripotent stem (iPS) cell-derived cardiomyocytes (CMs) may help to reveal cell phenotype characteristics resulting from different genetic backgrounds. The present study was to compare the structural and electrophysiological characteristics of sodium channel subunits with different genetic variations and evaluate the safety of quinidine for use with BrS patient-specific iPSC-derived cardiomyocytes.Methods: Two BrS patient-specific iPS cell lines were constructed that carried missense mutations in SCN5A and SCN1B. One iPS cell line from a healthy volunteer was used as a control. The differentiated cardiomyocytes from the three groups were evaluated by flow cytometry, immunofluorescence staining, electron microscopy, as well as calcium transient and patch clamp analyses to assess different pathological phenotypes. Finally, we evaluated the drug responses to varying concentrations of quinidine by measuring the action potential.Results: Compared to the control group, BrS-CMs showed a significant reduction in sodium current, prolonged action potential duration and varying degrees of decreased Vmax, but no structural difference was observed. After applying different concentrations of quinidine, the disease-specific groups and the control group had a downward trend in maximal upstroke velocity, resting membrane potential and action potential amplitude, and exhibited prolonged action potential duration without increasing incidence of arrhythmic events.Conclusion: Both patient-specific iPSC-CMs recapitulated the BrS phenotype at the cellular level. Although the SCN5A variation led to a markedly lower sodium current than what was observed with the SCN1B variation, their responses to quinidine were quite similar. The present study provides an advantageous platform for exploring disease mechanisms and evaluating drug safety in vitro.

scholarly journals Cellular Mechanism of the QT Prolongation Induced by Sulpiride

2009 ◽  
Vol 28 (3) ◽  
pp. 207-212 ◽  
Author(s):  
Hyang-Ae Lee ◽  
Ki-Suk Kim ◽  
Sang-Joon Park ◽  
Eun-Joo Kim
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Plasma Concentrations ◽  
Clinical Signs ◽  
Dependent Manner ◽  
Prolonged Action ◽  
Patch Clamp Technique ◽  
Concentration Dependent Manner ◽  
Severe Arrhythmia ◽  
Prolonged Action Potential Duration

In this study, the authors investigated the electrophysiological effect of sulpiride on cardiac repolarization using conventional microelectrode recording techniques in isolated canine Purkinje fibers and a whole-cell patch clamp technique in transiently transfected cells with the hERG, KCNQ1/KCNE1, KCNJ2, and SCN5A cDNA and in rat cardiac myocytes for ICa. In studies of action potential duration, 10 μM, 100 μM, 300 μM, and 1 mM sulpiride prolonged action potential duration in a concentration-dependent manner. In studies of cardiac ion channels, sulpiride did not significantly affect INa, ICa, IKs, IK1, except for IKr. Sulpiride dose-dependently decreased the hERG tail current. It is considered that the prolonged action potential duration by sulpiride was mainly the result of inhibition of the hERG channel. The data suggest that the clinical use of sulpiride is reasonable within therapeutic plasma concentrations, but all patients taking this drug should be cautiously monitored for clinical signs of long-QT syndrome and severe arrhythmia.

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