Liposome-Encapsulated Hemoglobin Vesicle Improves Persistent Anti-arrhythmogenesis through Improving Myocardial Electrical Remodeling and Modulating Cardiac Autonomic Activity in a Hemorrhagic Shock-Induced Rat Heart Model

Objective Shock heart syndrome(SHS)is associated with lethal arrhythmias(ventricular tachycardia/ventricular fibrillation,VT/VF).We investigated whether liposome-encapsulated human hemoglobin vesicles(HbVs)has comparable persistent efficacy to washed red blood cells(wRBCs)for improving arrhythmogenesis in the subacute to chronic phase of SHS.Methods Optical mapping analysis(OMP),electrophysiological study(EPS),and pathological examinations were performed on blood samples from Sprague-Dawley rats following induction of hemorrhagic shock.After hemorrhagic shock,the rats were immediately resuscitated by transfusing 5%albumin(ALB),HbV,or wRBCs.All rats survived for 1 week.OMP and EPS were performed on Langendorff-perfused hearts.Spontaneous arrhythmias and heart rate variability(HRV)were evaluated using awake 24-h telemetry,cardiac function by echocardiography,and pathological examination of Connexin43.Results OMP showed significantly impaired action potential duration dispersion(APDd)in the left ventricle(LV)in the ALB group whereas APDd was substantially preserved in the HbV and wRBCs groups.Sustained VT/VF was easily provoked by EPS in the ALB group.No VT/VF was induced in the HbV and wRBCs groups.HRV,spontaneous arrhythmias,and cardiac function were preserved in the HbV and wRBCs groups.Pathology showed myocardial cell damage and Connexin43 degradation in the ALB group,all of which were attenuated in the HbV and wRBCs groups.Conclusion LV remodeling after hemorrhagic shock caused VT/VF in the presence of impaired APDd.Similar to wRBCs,HbV persistently prevented VT/VF by inhibiting persistent electrical remodeling,preserving myocardial structures,and ameliorating arrhythmogenic modifying factors in the subacute to chronic phase of hemorrhagic shock-induced SHS.

Low-Molecular-Weight Heparin and Protamine-Based Polyelectrolyte Nano Complexes for Protein Delivery (A Review Articles)

We produced low-molecular-weight heparin/protamine micro (nano) particles (LMW-H/P MPs·NPs) as a carrier for heparin-binding growth factors (GFs), such as fibroblast growth factor (FGF)-2 and various GFs in platelet-rich plasma (PRP). A mixture of LMW-H (MW: approximately 5000 Da, 6.4 mg/ml) and protamine (MW: approximately 3000 Da, 10 mg/ml) at a ratio of 7:3 (vol:vol) yields a dispersion of micro (nano) particles (200 nm - 3 μm in diameter). The diluted LMW-H solution in saline (0.32 mg/ml) mixed with diluted protamine (0.5 mg/ml) at a ratio at 7:3 (vol:vol) resulted in soluble nanoparticles (approximately 100 nm in diameter). The generated NPs could be then stabilized by adding 2 mg/ml dextran (MW: 178-217 kDa) and remained soluble after lyophilization of dialyzed LMW-H /P NPs solution. The LMW-H/P MPs·NPs adsorb GFs, control their release, protect GFs and activate their biological activities. Furthermore, administration of GFs-containing F/P MPs·NPs exhibited significantly higher inductions of vascularization and fibrous tissue formation in vivo than GFs alone. LMW-H/P MPs·NPs can also efficiently bind to tissue culture plates and retain the binding of GFs. The LMW-H/P MPs·NP-coated matrix with various GFs or cytokines provided novel biomaterials that could control cellular activity such as proliferation and differentiation. Thus, LMW-H/P MPs·NPs are an excellent carrier for GFs and are a functional coating matrix for various kinds of cell cultures.