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Eur J Cardiothorac Surg 2003;24:974-985
© 2003 Elsevier Science NL

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

^a Anesthesiology Research Laboratory, Department of Anesthesiology, M4280, 8701 Watertown Plank Road, Medical College of Wisconsin, Milwaukee Regional Medical Center, Milwaukee, WI 53226, USA
^b Department of Physiology, Medical College of Wisconsin, Milwaukee Regional Medical Center, Milwaukee, WI 53226, USA
^c Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee Regional Medical Center, Milwaukee, WI 53226, USA
^d Department of Biomedical Engineering, Marquette University, Milwaukee, WI 53233, USA
^e Research Service, Veterans Affairs Medical Center, Milwaukee, WI 53295, USA

Received 14 November 2002; received in revised form 13 June 2003; accepted 16 June 2003.

^* Corresponding author. Tel.: +1-414-456-5722; fax: +1-414-456-6507
e-mail: dfstowe{at}mcw.edu

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/dt_max and d[Ca²⁺]_i/dt_min by 33 and 34%, sys–diaLVP by 55%, dLVP/dt_max and dLVP/dt_min 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.

Key Words: Magnesium • Calcium • Potassium • Perfusion solutions • Myocardium • Guinea pig

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