Sanguinarine Non- Versus Re-Circulation During Isolated Heart Perfusion - A Jekyll and Hyde Effect?

Abstract

Aims In isolated rat heart perfusion experiments, drug administration occurs via retrograde perfusion. This can be done in the non-recirculating mode (coronary effluent is discarded), or recirculating mode (coronary effluent is collected and reused). It was recently observed in our lab whi le using sanguinarine, an MKP-1 inhibitor, that there were differences in outcomes depending on the mode of recirculation used. Methods and ResultsHearts from control (C); diet-induced obese (DIO) Wis tar rats and their age matched controls (AMC) were perfused on the rig. Hearts received buffer (control), insulin, sang uinarine, insulin + sanguinarine combination or methanol (vehicle) fo r 15mins pre-and IOmins post-ischemia in either a non-or re-circulating manner. Hearts were subjected to I 5mins global ischemia and 30mins reperfusion. Mechanical function was documented pre-and postischemia When not-recirculated, sanguinarine alone and in combination with insulin in C, DIO and AMC groups, caused a significant decrease in functional recovery during reperfusion. However, when the coronary effluent was recirculated, hearts perfused with sanguinarine or sanguinarine + insulin exhibited a significant recovery in function when compared with their non-recirculation counterparts (p< 0.01). No differences were seen with either control, insulin nor vehicle hearts. Conclusion Sanguinarine elicited a vast improvement in perfu s ion outcomes when recirculated compared to nonrecirculation. Since this was seen during perfusion only

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