Abstract P296: Intralipid Protects the Heart Against Ischemia/Reperfusion Injury More Efficiently than Cyclosporine-A

Abstract

It has been shown that intralipid protects the heart against ischemia reperfusion (I/R) injury. Here we compared the cardioprotective effect of Intralipid (ILP) with cyclosporine-A (CsA), a potent inhibitor of the mitochondria permeability transition pore (mPTP) opening. Isolated hearts (Langendorff) from male mice were subjected to 20 minutes of global ischemia followed by reperfusion with Krebs Henseleit buffer (CTRL), additional 1% ILP (ILP group) or 1.5µM CsA (CsA group). The reperfusion duration was 40 min for measurement of cardiac function and infarct size, 10 min for measurement of mitochondrial calcium retention capacity and 5 min for superoxide production measurements using electron spin resonance. Post-ischemic administration of ILP improved the heart functional recovery even better than CsA as Rate pressure product (RPP) at the end of 40 min was significantly higher in ILP group compared to CsA group (13676±611 mmHg*beats/min (n=6) in ILP group vs. 7426±1158 mmHg*beats/min (n=3) in CsA, P<0.01). Consistent with the heart function, the infarct size was also significantly smaller in ILP compared to CsA group (18.3±2.4% (n=9) in ILP vs. 29.9±2.0% (n=3) in CsA, P<0.01). The heart functional recoveries were significantly higher and the infarct sizes were significantly smaller in both groups compared to CTRL (RPP=2999±863 mmHg*beats/min (n=6), the infarct size=54.8±2.9% (n=10)). ILP was as efficient as CSA in inhibiting mPTP opening as calcium retention capacity (CRC) was not significantly different between the mitochondria isolated from the heart which were reperfused with ILP or CSA (274.3±8.4 nM/mg-mitochondria protein (n=6) in ILP vs. 260.3±2.9 nM/mg-mitochondria protein (n=6) in CsA). The CRC in both groups were higher than CTRL (168.6±9.6 nM/mg mitochondria protein (n=7)). ILP prevented superoxide production in mitochondria similarly as CSA (0.344±0.1104 (n=4) in ILP vs. 0.5744±0.1445 (n=4) in CsA) which were significantly lower than CTRL (1±0.1197 (n=4), normalized to CTRL). In conclusion, although ILP inhibits the opening of the mPTP as efficiently as CsA, ILP is more effective than CsA in reducing the infarct size and improving the heart functional recovery.