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 while using sanguinarine, an MKP-1 inhibitor, that there were differences in outcomes depending on the mode of recirculation used.
Methods and Results
Hearts from control (C); diet-induced obese (DIO) Wistar rats and their age matched controls (AMC) were perfused on the rig. Hearts received buffer (control) , insulin, sanguinarine, insulin + sanguinarine combination or methanol (vehicle) for 15mins pre- and 10mins post-ischemia in either a non- or re-circulating manner. Hearts were subjected to 15mins global ischemia and 30mins reperfusion. Mechanical function was documented pre- and post-ischemia . 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 perfusion outcomes when recirculated compared to non-recirculation . Since this was seen during perfusion only when sanguinarine was present, it is possible that recirculating reperfusion of the drug caused profound changes in its composition. More investigation is needed into the mechanisms involved. Thus caution should be exercised by researchers when designing a perfusion protocol for drug research.
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Conflicts of Interest
There is no conflict of interest and all authors have disclosed no financial or personal relationship with organi zations that could potentially be perceived as influencing the described research.
All authors have read the journal’s authorship agreement and policy on disclosure of potential conflicts of interest. Funding: National Research Foundation, Harry Crossley Foundation, University of Stellenbosch
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Webster, I., Smith, A., Lochner, A. et al. Sanguinarine Non- Versus Re-Circulation During Isolated Heart Perfusion - A Jekyll and Hyde Effect?. Cardiovasc Drugs Ther 28, 489–491 (2014). https://doi.org/10.1007/s10557-014-6543-8
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DOI: https://doi.org/10.1007/s10557-014-6543-8