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Effects of Low Ca2+ and High Mg2+ Cardioplegic Solutions on Intracellular Ca2+ and Cardiac Function during Hypothermic Ischemia
Jianzhong An, M.D.; Amadou K.S. Camara, Ph.D.; Qun Chen, M.D., Ph.D.; Srinivasan G. Varadarajan, M.D.; David F. Stowe, M.D., Ph.D.
Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin
Background: Cold high K cardioplegia (CP) is used to rapidly induce cardiac arrest and reduce the risk of ischemic myocardial injury. We showed that CP decreased the rise in diastolic (dia)[Ca2+] observed during cold storage (3°C for 4 hours) in Krebs-Ringer's (KR) solution. Decreased dia[Ca2+] loading after CP leads to improved function on reperfusion. Increased solution Mg may counteract the effects of Ca2+ loading in ischemia reperfusion (IR) injury. In this study, we increased solution Mg, reduced solution Ca, or both, in CP solutions to examine their effects on cardiac mechanic function and [Ca2+] loading during and after moderate hypothermia ischemia (17°C for 4 hours) in isolated guinea pig hearts.

Methods: Guinea pig hearts were isolated and perfused at 55 mmHg with normal KR solution (37.5°C, Ca 2.5 mM, Mg 2.4 mM). Isovolumetric LVP and + and - dLVP/dt were measured. Hearts were loaded with 6 μM indo 1-AM and a trifurcated fiberoptic cable was placed at the LV free wall to excite and sample fluorescence emissions at 384 and 456 nm. F385/F456 was corrected for background, mitochondrial, and the ischemia-induced increase in NADH fluorescence. sys and dia[Ca2+] transients were calibrated to nM. After 30 min stabilization, 30 min dye or vehicle loading and 20 min wash out, hearts were subjected to 4 hours 17°C hypothermic ischemia and 60 minutes reperfusion.

Results: There were 5 randomized groups perfused with different solutions (in mM): a) 2.5 Ca + 2.4 Mg + 4.5 K (KR Control); b) 2.5 Ca + 7.2 Mg + 18 K (CP1); c) 1.25 Ca + 7.2 Mg + 18 K (CP2); and d) 2.5 Ca + 2.4 Mg + 18 K (CP3); e) 1.25 Ca + 2.4 Mg + 18 K (CP4). We found that d[Ca2+]/dtmax, d[Ca2+]/dtmin and dLVP/dtmax, dLVP/dtmin, coronary flow, cardiac efficiency and MVO2 were significantly higher in all CP groups compared to the KR group after 60 min warm reperfusion. CP reduced myoplasmic Ca2+ loading during cooling, ischemia and rewarming better than KR alone. On reperfusion after CP in each group, sys and phasic [Ca2+] were higher and dia[Ca2+] was lower. However, there was no differences in these indices among the 4 CP groups after reperfusion with KR solution.

Conclusion: This study demonstrates that increasing external K to produce cardiac arrest, which lowers [Ca2+], is the most protective effect of cardioplegia; halving external Ca or tripling external Mg does not add to this protective effect or additionally alter [Ca2+].

Anesthesiology 2002; 96: A604