Abstract P216: Sphingosine 1-Phosphate Improves Cardiac Dysfunction Induced by Hyperglycemia in Scavenger Receptor B Type I-Deficient, Hypomorphic Apolipoprotein ER61 Mice
Coronary artery disease (CAD) occurs in scavenger receptor B type I - deficient, hypomorphic apolipoprotein ER61 mice (SR-BI KO/ApoeR61h/h) fed a high fat diet. Acute hyperglycemia is a serious problem in intensive care units. We tested the hypothesis that sphingosine 1-phosphate (S1P) is cardioprotective in the presence of acute hyperglycemia. Three-month old SR-B1 KO/ApoeR61h/h mice were fed a high-fat diet or chow for 4 weeks. Isolated hearts were subjected to brief ischemia (25 min) followed by 2 hr of reperfusion. The perfusion buffer contained either 5.5 mM glucose, 33 mM glucose, or 33 mM mannitol as an osmotic control. This protocol yielded a small infarct size in normoglycemic hearts from mice receiving a normal chow diet. CAD hearts subjected to high glucose had very poor recovery of left ventricular developed pressure (LVDP) at the end of reperfusion (Panel A) and very large infarcts compared both to normoglycemic hearts and to hearts from mice fed normal chow subjected to hyperglycemia (Panel B). Hearts pretreated with 10 nM S1P for 2 min before the index ischemia exhibited a marked reduction in infarct size and LVDP was preserved. Mannitol had no effect on infarct size.
Conclusions: hyperglycemia damages hearts isolated from SR-BI KO/ApoeR61h/h mice and S1P exerts cardioprotection. RA=risk area; Glu=glucose; Mann. =mannitol. n=3–5/group; *=P<0.05 vs. all other conditions.