Background: 

Postconditioning (PC) is a widely studied way to limit cardiac damage after ischemia. The mechanisms involved are incompletely understood, but roles for delayed pH recovery have been addressed. Here, we investigated the effects of brief acidic reperfusion, or of inhibition of the Na⁺/H⁺ exchanger NHE1 by EIPA at onset of reperfusion, on ischemia/reperfusion (I/R) damage in Langendorf-perfused rat hearts and cultured HL-1 mouse cardiomyocytes.

Methods: 

Langendorf-perfused rat hearts were exposed to 35 min global no-flow ischemia and 120 min reperfusion. Treatments at onset of reperfusion were: (i) control (Krebs-Henseleit, pH 7.4); (ii) 15 min pH 6.5; (iii) 6x10 s reperfusion/ischemia cycles (PC), and (iv) 15 min EIPA (3 mM). HL-1 cardiomyocytes were treated similarly, with simulated I/R conducted in a closed incubator-workstation unit.

Results: 

Left ventricular end diastolic pressure (LVeDP) and infarct size were reduced by PC or acidic reperfusion, LVeDP more so after acidic reperfusion. Left ventricular developed pressure (LVDP) recovery was improved by acidic reperfusion yet not by PC. In contrast, EIPA modestly increased LVeDP and infarct size, and significantly attenuated LVDP recovery. In HL-1 cardiomyocytes in presence of HCO₃^- (allowing pH_i-regulation via HCO₃^--dependent mechanisms) I/R elicited JNK-, Akt- and caspase-3 activation, PARP cleavage and necrosis, neither of which were reduced by acidic reperfusion or EIPA.

Conclusion: 

Both PC and acidic reperfusion improved myocardial performance after I/R in whole hearts, yet to a different extent, whereas inhibition of NHE1 was detrimental. The protection of intact hearts by acidic reperfusion could not be mimicked in HL-1 cardiomyocytes.