Effect of aging on intracellular Ca2+, pHi, and contractility during ischemia and reperfusion

Abstract

Background: To investigate the effect of aging on myocardial ischemic and reperfusion injury, cytosolic calcium (Ca2+), intracellular pH (pHi), and mechanical performance were measured in isolated perfused rabbit hearts.

Methods and results: Hearts of mature (4-5-month-old) and aged (28-38-month-old) rabbits were loaded with 10 microM of fura-2 or 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and subjected to 30 minutes of normothermic ischemia and reperfusion. Cytosolic Ca2+ levels ([Ca2+]) during the nonbeating ischemic period and end-diastolic Ca2+ levels ([EDCa2+]) during reperfusion were determined from the fura-2 fluorescence ratio of emission at 510 nm during excitation at 340 and 380 nm. pHi was obtained from the ratio of emission at 530 nm during excitation at 450 and 490 nm. [Ca2+] of the mature group (n = 8) increased from 188 +/- 19 nM (mean +/- SEM) to 373 +/- 32 nM during ischemia, and that of the aged group (n = 7) increased from 242 +/- 17 to 465 +/- 20 nM. The rise of [Ca2+] of the aged group was significantly greater (p < 0.05) than that of the mature group. Immediately after reperfusion, [EDCa2+] in both groups returned to the preischemic level. pHi decreased to the same extent (from 7.2 to 6.7) during ischemia and returned to preischemic values during reperfusion. The mature group recovered 84 +/- 3% of left ventricular peak pressure after ischemia, whereas the aged group recovered only 55 +/- 3% (p < 0.005). Functional recovery was inversely correlated to the increase of [Ca2+] during ischemia (r = 0.66).

Conclusions: Aged hearts exhibit greater accumulation of [Ca2+] during ischemia and less functional recovery after ischemia than mature hearts. The greater rise of [Ca2+] in aged hearts is not a result of the difference of buffering capacity for ischemia-induced acidosis.