The effect of sphingosine-1-phosphate on the endothelial glycocalyx during ischemia-reperfusion injury in the isolated rat heart.

OBJECTIVE

Sphingosine-1-phosphate is a natural metabolite that is cardioprotective, but its effects on endothelial glycocalyx damage during ischemia-reperfusion are unknown. Therefore, we investigated the effect of sphingosine-1-phosphate on the endothelial glycocalyx during ischemia-reperfusion.

METHODS

Isolated hearts from Wistar rats were perfused on a Langendorff system with Krebs-Henseleit buffer and pretreated with sphingosine-1-phosphate (10 nmol/L) before ischemia-reperfusion. Infarct size was measured by triphenyl tetrazolium chloride staining (n ≥ 6 per group). Cardiac edema was assessed by calculating total water content (n = 7 per group) and histologically quantifying the interstitial compartment (n ≥ 3 per group). The post-ischemic coronary release of syndecan-1 was quantified using ELISA. Syndecan-1 immunostaining intensity was assessed in perfusion-fixed hearts (n ≥ 3 per group).

RESULTS

Pretreatment with sphingosine-1-phosphate decreased infarct size in isolated hearts subjected to ischemia-reperfusion (P = .01 vs ischemia-reperfusion). However, sphingosine-1-phosphate had no effect on syndecan-1 levels in the coronary effluent or on the intensity of the syndecan-1 immunostaining signal in cardiac tissue. Heart total water content was not significantly different between control and ischemic groups but was significantly decreased in hearts treated with sphingosine-1-phosphate alone.

CONCLUSION

These results suggest that sphingosine-1-phosphate-induced cardioprotection against ischemia-reperfusion injury is not mediated by the maintenance of syndecan-1 in the endothelial glycocalyx.