Cardioplegic Strategies for Calcium Control

Background—Ca21 overload plays an important role in the pathogenesis of cardioplegic ischemia-reperfusion injury. The standard technique to control Ca21 overload has been to reduce Ca21 in the cardioplegic solution (CP). Recent reports suggest that Na1/H1 exchange inhibitors can also prevent Ca21 overload. We compared 4 crystalloid CPs that might minimize Ca21 overload in comparison with standard Mg21-containing CP: (1) low Ca21 CP (0.25 mmol/L), (2) citrate CP/normal Mg21 (1 mmol/L Mg21), (3) citrate CP/high Mg21 (9 mmol/L Mg21), and (4) the addition of the Na1/H1 exchange inhibitor HOE-642 (Cariporide). We also tested the effect of citrate titration in vitro on the level of free Ca21 and Mg21 in CPs. Methods and Results—Isolated working rat heart preparations were perfused with oxygenated Krebs-Henseleit buffer and subjected to 60 minutes of 37°C arrest and reperfusion with CPs with different Ca21 concentrations. Cardiac performance, including aortic flow (AF), was measured before and after ischemia. Myocardial high-energy phosphates were measured after reperfusion. The in vitro addition of citrate to CP (2%, 21 mmol/L) produced parallel reductions in Mg21 and Ca21. Because only Ca21 was required to be low, the further addition of Mg21 increased free Mg21, but the highest level achieved was 9 mmol/L. Citrate CP significantly impaired postischemic function (AF 58.362.5 % without citrate versus 41.663 % for citrate with normal Mg21, P,0.05, versus 22.466.2 % for citrate with high Mg21, P,0.05). Low-Ca21 CP (0.25 mmol/L Ca21) significantly improved the recovery of postischemic function in comparison with standard CP (1.0 mmol/L Ca21) (AF 47.661.7 % versus 58.362.5%, P,0.05). The addition of HOE-642 (1 mmol/L