Document Detail


Sanguinarine Non- Versus Re-Circulation During Isolated Heart Perfusion - A Jekyll and Hyde Effect?
MedLine Citation:
PMID:  25022545     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
I Webster; A Smith; A Lochner; B Huisamen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-16
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  -     ISSN:  1573-7241     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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