Improved mitochondrial Ca 2+ handling and functional recovery after ischemia reperfusion injury in hearts from old vs. young guinea pigs

Abstract

We hypothesized that aging-induced oxidative damage to mitochondria would result in mitochondrial [Ca2+] (m[Ca2+]) overload, depressed contractile function, and decreased NADH after ischemia reperfusion (IR) injury in old vs. young guinea pig hearts. Unpaced hearts (n=7 each) from young (< 2 mo) and old (> 24 mo) animals were perfused with Krebs-Ringer’s solution (2.1 mM [Ca2+]) at 37°C. Left ventricular pressure (LVP, mmHg) was recorded with a saline filled latex balloon and transducer. Simultaneously, m[Ca2+] (nM) was measured ratiometrically by indo-1 fluorescence with a fiber optic probe on the LV free wall. Hearts were subjected to 30 min global ischemia and 60 min reperfusion (RP). All data ± SEM, p<0.05 vs. old. We found: No difference at baseline in developed LVP (systolic-diastolic), diastolic LVP, or m[Ca2+] in old vs. young hearts. Developed LVP was higher at RP10 and RP60 in old (57±11 and 55±10) vs. young (29±2 and 32±2) hearts. Diastolic LVP was lower at RP10 and RP60 in old (9±2 and 7±2) vs. young (20±2 and 14±2) hearts. m[Ca2+] was lower at RP10 and RP 60 in old (129±2 and 122±2) vs. young (293±23 and 234±15) hearts. Contrary to our initial hypothesis, old hearts showed reduced m[Ca2+] loading and improved mechanical function after IR injury compared to young hearts. There were no differences in redox state due to age. Aging associated protection may be linked to better collateral vessel formation, better preservation of contractile apparatus, or preconditioning mechanisms from prior stress. (AHA, NIH)