The differential effects of FTY720 on functional recovery and infarct size following myocardial ischaemia/reperfusion

The aim of this study was to evaluate the effects of the sphingosine analogue, FTY720 (Fingolimod), on the outcomes of myocardial ischaemia/reperfusion (I/R) injury. Two concentrations of FTY720 (1 or 2.5 µM were administered either prior to (PreFTY), or following (PostFTY) 20 minutes' global (GI) or 35 minutes' regional ischaemia (RI) in the isolated, perfused, working rat heart. Functional recovery during reperfusion was assessed following both models of ischaemia, while infarct size (IFS) was determined following RI. FTY720 at 1 µM exerted no effect on functional recovery, while 2.5 µM significantly impaired aortic output (AO) recovery when administered prior to GI (% recovery: control: 33.88 ± 6.12% vs PreFTY: 0%, n = 6-10; p < 0.001), as well as before and after RI ( % recovery: control: 27.86 ± 13.22% vs PreFTY: 0.62% ; p < 0.05; and PostFTY: 2.08%; p = 0.0585, n = 6). FTY720 at 1 µM administered during reperfusion reduced IFS (% of area at risk (AAR): control: 39.89 ± 3.93% vs PostFTY: 26.56 ± 4.32%, n = 6-8; p < 0.05), while 2.5 µM FTY720 reduced IFS irrespective of the time of administration ( % of AAR: control: 39.89 ± 3.93% vs PreFTY: 29.97 ± 1.03% ; and PostFTY: 30.45 ± 2.16%, n = 6; p < 0.05). FTY720 exerted divergent outcomes on function and tissue survival depending on the concentration administered, as well as the timing of administration.