Novel strategies to improve myocardial performance and diminish capillary leak after cardiac surgery and cardiopulmonary bypass in children utilising P188
Background. Poloxomar 188(P188) is a non-ionic surfactant associated with improved blood viscosity and plasma membrane protection in human and experimental contexts respectively. We recently reported use of P188 in a lamb CPB model and demonstrated improved haemodynamics, reduced haemodilution and reduced membrane injury. We sought to elucidate its mechanisms of action utilising a Langendorff model.
Methods. Rat hearts were perfused using a crystalloid perfusate ąP188. Flow was maintained for 120min(n=12) or temporarily suspended for 30min(n=12) to model ischaemia. A low dose(0.42mg/ml) was followed by a clinically relevant high dose(150mg/ml). Myocardial function was assessed by LV developed pressure. Myocardial water content(MWC) was measured.
Results. In low dose and non-ischaemic hearts, P188 was associated with a reduction in MWC, 0.78 vs. 0.82, p=0.03. There was no effect on MWC in the ischaemic hearts and no difference in myocardial function between groups. At high dose in ischaemia, P188 was associated with a trend towards improved diastolic function, p=0.06, but no difference in MWC.
Conclusion. Neither the diminished myocardial water accumulation or trend toward better diastolic function can be well explained by previously described rheological effects of P188 in this asanguinous model. Reduced MWC could be explained by diminished endothelial leak in the face of endothelial activation. Improved myocardial performance may relate to previously proposed mechanisms including membrane sealing to minimise intracellular calcium overload. The effects of P188 on the microcirculation and myocyte membrane as well as dose finding experiments are required with a view to using P188 in the context of cardiac surgery.