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
Inhibition of MKP-1 with sanguinarine abolished the insulin-induced improvement in functional recovery, but reduced infarct size. Although the data suggest a role for this phosphatase in insulin-induced cardioprotection, the multiple downstream effects of insulin hamper interpretation of the data obtained. In addition, the effects of sanguinarine per se in myocardial ischaemia/reperfusion need to be further elucidated.
This group of women was well informed regarding current indications and developments concerning HT. Despite their socioeconomic status, the doctor remained the key factor with regard to information and decision-making.
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