Abstract 272: Intralipid Protects Late Pregnant Mouse Heart Against Ischemia/Reperfusion Injury More Efficiently than Cyclosporine-A

Abstract

Introduction Recently, we found that hearts of late pregnant (LP) mice have higher vulnerability to ischemia/reperfusion (I/R) injury compared to hearts of non-pregnant mice. We also found intralipid (ITLD), a clinically safe compound protects the male rodent hearts against I/R injury if administrated at reperfusion. Here we explored whether ITLD can protect the function of LP mouse hearts against I/R injury, and compared its action with cyclosporine-A (CsA), a potent inhibitor of mithochondrial permeability transition pore (mPTP) opening. Methods Isolated LP mouse hearts were subjected to 20 min ischemia followed by reperfusion with i) Krebs Henseleit buffer (CTRL), ii) additional 1% ITLD or iii) 1.5µM CsA. The duration of reperfusion was 40 min for heart functional measurements and infarct size assessment and 10 min for measurements of mitochondrial calcium retention capacity (CRC). Two way ANOVA was used for statistical analysis. P<0.05 were considered statistically significant. Values are expressed as mean± SEM. Results The heart functional recovery of LP mice after ischemia was very poor. Postischemic administration of ITLD significantly improved the cardiac function of LP mice; the rate pressure product (RPP) at the end of reperfusion was improved from 1614±438 mmHg*beats/min (n=4) to 11556±784 mmHg*beats/min (n=3) with addition of ITLD. The infarct size was also significantly reduced by ITLD to 17±2% (n=3) from 59±5% (n=4) in CTRL (P<0.01). Interestingly, ITLD was even more efficient than CsA in protecting the hearts of LP mice against ischemia reperfusion injury as in CsA group the RPP was significantly lower at the end of reperfusion (5960±1332, n=4) and the infarct size was larger (25±3%, n=4) compared to ITLD(P<0.05). ITLD-induced cardioprotection of LP mouse hearts against I/R was associated with a delay in the opening of the mPTP similar to CsA. The calcium load required for triggering the opening of the mPTP increased from 180±7 nM/mg (n=6) protein in CTRL to 290±12 nM/mg (n=6) protein in ITLD (P<0.01), which was not significantly different than 276±20 nM/mg protein in CsA group. Conclusion ITLD protects late pregnant mouse hearts against I/R injury more efficiently than CsA by inhibiting the mPTP opening.