Improving cardiac function with new-generation plasma volume expanders

Abstract

Background Plasma expander (PE) based on polyethylene glycol (PEG) conjugated to albumin has shown positive results maintaining blood volume (BV) during hemodilution and restoring BV during resuscitation from hemorrhagic shock. PEG conjugation to human serum albumin (HSA), PEG-HSA, increasing size, weigh and colloidal osmotic pressure (COP), with minor effects on solution viscosity. Methods This study was designed to test the hypothesis that PEG-HSA (2 g/dL) produced by direct PEGylation chemistry improves cardiac function during two experimental models, i) moderate hemodilution and ii) resuscitation from hemorrhagic shock, compared to a conventional colloidal plasma expander (dextran 70 kDa, D×70, 6 g/dL). Cardiac function was studied using a miniaturized pressure volume (PV) conductance catheter implanted in the left ventricle (LV) and evaluated in terms of cardiac indices derived from the PV measurements. Results PEG-HSA increased cardiac output (CO), stroke volume (SV) and stroke work (SW), and decreased systemic vascular resistance (SVR) compared to D×70, in both experimental models. The improvements induced by PEG-HSA in cardiac function were sustained over the observation time. PEG-HSA cardiac mechanoenergetics changes are the result of increased energy transferred per stroke, and decreased resistance of the vasculature connecting the heart. In summary, PEG-HSA decreased LV ejection impedance. Conclusion Ejection of blood diluted with PEG-HSA presented a reduced load to the heart, increased contractile function, and lowered the energy consumed per unit volume compared to D×70. Our results emphasize the importance of heart function as a parameter to be included in the evaluation changes induced by new PEs.

Infusion Antihypoxants in Children with Critical Conditions

“…A number of experimental studies with the aim to evaluate the efficiency of polyethylene glycol also demon strated its positive effects [49,50].…”

“…В ряде зарубежных исследований, посвященных оценке эффективности использования полиоксифума рина у детей, также были продемонстрированы его по ложительные эффекты [49,50].…”

Blood Substitutes

“…In particular the inherent hemodilution associated with its introduction and it is shear thinning endowing properties reduces blood viscosity in the heart, therefore reducing its workload. 30, 81 …”

The Effect of Length and Structure of Attached Polyethylene Glycol Chain on Hydrodynamic Radius, and Separation of PEGylated Human Serum Albumin by Chromatography

“…However, as macromolecules leak continuesly into the interstitial space, this expanding effect of albumin is not enough, and so frequent HSA infusion is necessary in order to manage the interstitial edema, and to maintain the demanded blood concentration 8,11 . As the size of HSA's molecule has very important role in its retention during the circulation, therefore increased hydrodynamic radius of HSA by PEGylation, makes it an excellent volume expander that can prevent the interstitial edema, and reduce its infusion peridicity 8,12 . PEG which is biocompatible and non-immunogenic polymer has wide application in protein conjugation 13 , that as a result the size of protein increases and so the possibility of its leakages decreases 2,3 .…”