Abstract
SummaryAimThe 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.MethodsTwo 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.ResultsFTY720 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).ConclusionFTY720 exerted divergent outcomes on function and tissue survival depending on the concentration administered, as well as the timing of administration.
Highlights
There were no significant differences in the basal capacity of any of the groups compared to the control
Administration of FTY720 at a dose of 1 μM had no effect on functional recovery (Fig. 3), irrespective of whether it was administered before ischaemia or during early reperfusion
Similar to the effects associated with 1 μM, reperfusion administration of 2.5 μM FTY720 did not exert any significant effects on post-ischaemic function (Fig. 4)
Summary
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. The aim of this study was to investigate and describe the effects of FTY720 administration at two different concentrations (1 and 2.5 μM) prior to ischaemia or at the onset of reperfusion in two different models of ischaemia (20 minutes’ global ischaemia and 35 minutes’ regional ischaemia) on different endpoints in the isolated, working rat heart model
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