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.

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.

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.

Abstract 116: Acute and Chronic Anti-Arrhythmogenic Effect of Liposome-Encapsulated Hemoglobin (HbV) on the Myocardium Through Improving Myocardial Electrical Remodeling and the Arrhythmogenic Substrate in Hemorrhagic Shock-Induced Heart

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Bonpei Takase ◽  
Yuko Higashimura ◽  
Kenichi Hashimoto
Keyword(s):  
Left Ventricle ◽  
Hemorrhagic Shock ◽  
Structural Damage ◽  
Cell Damage ◽  
Electrophysiological Study ◽  
Chronic Phase ◽  
Electrical Remodeling ◽  
Sprague Dawley ◽  
Total Blood ◽  
Arrhythmogenic Substrate

Introduction: Prolonged blood pressure < 40 mmHg in hemorrhagic shock (HS) causes irreversible heart dysfunction, “Shock Heart Syndrome” (SHS), which is associated with lethal arrhythmias (VT/VF). Methods: To investigate whether liposome-encapsulated human hemoglobin (HbV) is comparable to washed red blood cells (wRBCs) for improving arrhythmogenesis in SHS in either acute or chronic phase, optical mapping analysis (OMP), electrophysiological study (EPS) and pathological examinations were performed in Sprague-Dawley rat hearts, being obtained from both acute and chronic phase when each rat survived. The first, they were subjected to acute HS by withdrawing 30% of total blood volume. After HS, rats were immediately resuscitated by transfusing exactly same amount of 5% albumin (5%ALB, n=13), HbV (n=13), or wRBCs (n=13). All rats in chronic phase survived at least several weeks. After excising heart, OMP and EPS were performed in Langendorff-perfused hearts. Results: In both acute and chronic phase, OMP showed tendency for abnormal conduction and significantly impaired action potential duration dispersion (APDd) in left ventricle with 5%ALB (25±9 / 24±10 ms, Acute / Chronic phase). In contrast, myocardial conduction and APDd were substantially preserved with HbV (14±3 / 13±5 ms) and wRBCs (14±3 / 15±3 ms) as shown in Figure . Sustained VT/VF was easily provoked by burst pacing stimulus to left ventricle with 5%ALB. No VT/VF was induced with HbV and wRBCs. Pathology showed myocardial structural damage characterized by worse myocardial cell damage and Connexin43 with 5%ALB, whereas it was attenuated with HbV and wRBCs in both acute and chronic phase. Conclusions: Ventricular structural remodeling after HS causes VT/VF in the presence of APDd. Transfusion of HbV prevents acutely and chronically VT/VF, similarly to transfusion of wRBCs, by preventing chronic electrical remodeling of APDd and preserving myocardial structures in HS-induced SHS

Effects of thyroid hormone on action potential and repolarizing currents in rat ventricular myocytes

2000 ◽  
Vol 278 (2) ◽  
pp. E302-E307 ◽  
Author(s):  
Zhuo-Qian Sun ◽  
Kaie Ojamaa ◽  
William A. Coetzee ◽  
Michael Artman ◽  
Irwin Klein
Keyword(s):  
Action Potential ◽  
Cardiac Electrophysiology ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Mechanisms Of Action ◽  
Transient Outward Current ◽  
Prolonged Action ◽  
Electrophysiological Properties ◽  
Whole Cell Patch Clamp ◽  
Prolonged Action Potential Duration

Thyroid hormones play an important role in cardiac electrophysiology through both genomic and nongenomic mechanisms of action. The effects of triiodothyronine (T3) on the electrophysiological properties of ventricular myocytes isolated from euthyroid and hypothyroid rats were studied using whole cell patch clamp techniques. Hypothyroid ventricular myocytes showed significantly prolonged action potential duration (APD90) compared with euthyroid myocytes, APD90 of 151 ± 5 vs. 51 ± 8 ms, respectively. Treatment of hypothyroid ventricular myocytes with T3 (0.1 μM) for 5 min significantly shortened APD by 24% to 115 ± 10 ms. T3 similarly shortened APD in euthyroid ventricular myocytes, but only in the presence of 4-aminopyridine (4-AP), an inhibitor of the transient outward current ( I to), which prolonged the APD by threefold. Transient outward current ( I to) was not affected by the acute application of T3 to either euthyroid or hypothyroid myocytes; however, I to density was significantly reduced in hypothyroid compared with euthyroid ventricular myocytes.

scholarly journals Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium

2018 ◽  
Vol 315 (5) ◽  
pp. H1091-H1100 ◽  
Author(s):  
Jeevan Kumar Jadapalli ◽  
Griffin W. Wright ◽  
Vasundhara Kain ◽  
Mohammad Asif Sherwani ◽  
Ravi Sonkar ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Structural Changes ◽  
Low Dose ◽  
Chronic Phase ◽  
Saline Control ◽  
Control Group ◽  
High Dose ◽  
Saline Control Group ◽  
Inflammation Resolution ◽  
Acute And Chronic Exposure

Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-month-old male C57BL/6J mice were divided into high- and low-dose DOX-treated groups with a maintained saline control group. The first group was injected with a high dose of DOX (H-DOX; 15 mg·kg−1·wk−1), and the second group was injected with 7.5 mg·kg−1·wk−1 as a latent low dose of DOX (LL-DOX). H-DOX treatment led to complete mortality in 2 wk and 70% survival in the LL-DOX group compared with the saline control group. Therefore, an additional group of mice was injected with an acute high dose of DOX (AH-DOX) and euthanized at 24 h to compare with LL-DOX and saline control groups. The LL-DOX and AH-DOX groups showed obvious apoptosis and dysfunctional and structural changes in cardiac tissue. Splenic contraction was evident in AH-DOX- and LL-DOX-treated mice, indicating the systems-wide impact of DOX on integrative organs of the spleen, which is essential for cardiac homeostasis and repair. DOX dysregulated splenic-enriched immune-sensitive lipoxygenase and cyclooxygenase in the spleen and left ventricle compared with the saline control group. As a result, lipoxygenase-dependent D- and E-series resolvin precursors, such as 16HDoHE, 4HDoHE, and 12-HEPE, as well as cyclooxygenase-mediated PG species (PGD2, PGE2, and 6-keto-PG2α) were decreased in the left ventricle, suggestive of defective immunometabolism. Both AH-DOX and LL-DOX induced splenic contraction and expansion of red pulp with decreased CD169+ metallophilic macrophages. AH-DOX intoxicated macrophages in the spleen by depleting CD169+ cells in the acute setting and sustained the splenic macrophage loss in the chronic phase in the LL-DOX group. Thus, DOX triggers a vicious cycle of splenocardiac cachexia to facilitate defective immunometabolism and irreversible macrophage toxicity and thereby impaired the inflammation-resolution program. NEW & NOTEWORTHY Doxorubicin (DOX) triggered splenic mass loss and decreased CD169 with germinal center contraction in acute and chronic exposure. Cardiac toxicity of DOX is marked with dysregulation of immunometabolism and thereby impaired resolution of inflammation. DOX suppressed physiological levels of cytokines and chemokines with signs of splenocardiac cachexia.

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