Effect of low [CaCl2] and high [MgCl2] cardioplegia and moderate hypothermic ischemia on myoplasmic [Ca2+] and cardiac function in intact hearts

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Abstract
Objective: Cold cardioplegia (CP) protects against ischemic damage in part by reducing [Ca2+]i overload on reperfusion. Hyperkalemic cardioplegic solutions are widely used in coronary artery bypass procedures, and the specific ionic composition of these solutions may contribute to their variable myocardial protective effects secondary to reduced Ca2+i loading. We reported previously that CP decreased the rise in cardiac diastolic (dia) [Ca2+]i observed during 4 h cold storage at 3 °C in Krebs–Ringer's (KR) solution and decreased dia[Ca2+]i and increased systolic (sys) [Ca2+]i and function on reperfusion after cold storage. Our aim here was to determine if low Ca2+o and high Mg2+o adds to the protective effects of high K+o by decreasing [Ca2+]i during ischemia and reperfusion. Methods: We compared effects of 4.5 mM K+o, 2.5 mM Ca2+o and 2.4 mM Mg2+o KR solution with a higher K+o (18 mM), a lower Ca2+o (1.25 mM) and/or higher Mg2+o (7.2 mM) CP solutions on cardiac mechanic function and sys and dia[Ca2+]i during and after moderate hypothermic global ischemia (17 °C for 4 h) in guinea pig intact hearts isolated by the Langendorff technique. Isovolumetric left ventricular pressure (LVP) was measured with a transducer connected to a fluid-filled balloon placed in the LV and [Ca2+]i was measured using indo-1 fluorescence and a fiberoptic cable placed on the LV free wall. Results: For all CP groups compared to the KR control group after 60 min reperfusion, we observed significant lowering of dia[Ca2+]i by 47%, left ventricular diastolic pressure (diaLVP) by 55%, and infarct size by 43%. We also found significant elevation of sys[Ca2+]i by 25%, d[Ca2+]i/dtmax and d[Ca2+]i/dtmin by 33 and 34%, sys–diaLVP by 55%, dLVP/dtmax and dLVP/dtmin by 34 and 40%, coronary flow by 31%, cardiac efficiency by 21%, and MVO2 by 25%. These results indicate that CP reduces myoplasmic Ca2+ loading and improves mechanical and metabolic function on warm reperfusion compared to KR. However, there were no differences in these indices of Ca2+i cardiac function or metabolism among any CP group after warm reperfusion with KR solution. Conclusion: Increasing K+o to produce cardiac arrest was the most cardioprotective effect of CP against ischemia reperfusion injury; lowering Ca2+o or raising Mg2+o did not add to this protective effect or additionally alter [Ca2+]i.

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