Cardioplegic Strategies for Calcium Control

Background—Ca overload plays an important role in the pathogenesis of cardioplegic ischemia-reperfusion injury. The standard technique to control Ca overload has been to reduce Ca in the cardioplegic solution (CP). Recent reports suggest that Na/H exchange inhibitors can also prevent Ca overload. We compared 4 crystalloid CPs that might minimize Ca overload in comparison with standard Mg-containing CP: (1) low Ca CP (0.25 mmol/L), (2) citrate CP/normal Mg (1 mmol/L Mg), (3) citrate CP/high Mg (9 mmol/L Mg), and (4) the addition of the Na/H exchange inhibitor HOE-642 (Cariporide). We also tested the effect of citrate titration in vitro on the level of free Ca and Mg 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 Ca 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 Mg and Ca. Because only Ca was required to be low, the further addition of Mg increased free Mg, 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 Mg, P,0.05, versus 22.466.2% for citrate with high Mg, P,0.05). Low-Ca CP (0.25 mmol/L Ca) significantly improved the recovery of postischemic function in comparison with standard CP (1.0 mmol/L Ca) (AF 47.661.7% versus 58.362.5%, P,0.05). The addition of HOE-642 (1 mmol/L) to CP significantly improved postischemia function (47.661.7% without HOE-642 versus 62.461.7% with HOE-642, P,0.05). Postischemia cardiac high-energy phosphate levels were unaffected by Ca manipulation. Conclusions—(1) A lowered Ca concentration in CP is beneficial in Mg-containing cardioplegia. (2) The use of citrate to chelate Ca is detrimental in the crystalloid-perfused isolated working rat heart, especially with high Mg. (3) The mechanism of citrate action is complex, and its use limits precise simultaneous control of Ca and Mg. (4) HOE-642 in CP is as efficacious in preservation of the ischemic myocardium as is the direct reduction in Ca. (Circulation. 2000;102[suppl III]:III-319-III-325.)