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Eur J Cardiothorac Surg 2002;22:944-950
© 2002 Elsevier Science NL

The role of Na⁺/H⁺ exchange in the efficacy of multidose hypothermic cardioplegia in immature rabbit hearts

Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Kita-14, Nishi-5, Kita-ku, Sapporo 060-8648, Japan

Received 11 February 2002; received in revised form 25 July 2002; accepted 4 September 2002.

* Corresponding author. Tel.: +81-11-716-1161; fax: +81-11-747-0476
e-mail: muratosh{at}med.hokudai.ac.jp

Objectives: Recent studies have demonstrated that the use of a Na⁺/H⁺ exchange inhibitor as an additive can enhance the cardioprotective efficacy of cardioplegia in the adult heart under both normothermic and hypothermic conditions. However, few references are available as to the cardioprotective effect of acidic cardioplegia or Na⁺/H⁺ exchange inhibitors in the neonatal heart, particularly under hypothermic conditions. Methods and results: In isolated working hearts from rabbits aged 7–10 days, function was assessed prior to 10 h of ischemia (20 °C) and again after 35 min of reperfusion. All hearts received a pre-ischemic infusion (10 ml) of cardioplegic solution (20 °C) at pH 7.8, followed by nine subsequent infusions (5 ml every 1 h) of cardioplegic solution (20 °C) at pH 6.6, 7.0, 7.4, 7.8 (control) or 8.2 (n=8/group). When the pH was increased to 8.2, post-ischemic recovery of cardiac output was reduced and cumulative creatine kinase (CK) leakage during cardioplegic infusions was increased. In contrast, when the pH of the cardioplegic solution was lowered to 6.6, the post-ischemic recovery of cardiac output was maintained and CK leakage was reduced. Next, the effects of 5-(N,N-dimethyl)amiloride (DMA), an inhibitor of Na⁺/H⁺ exchange, were investigated. The inclusion of DMA in the pH 8.2 solution improved the post-ischemic recovery of cardiac output from 12.6±4.1% to 52.0±3.0% (P<0.0001) and reduced cumulative CK leakage during cardioplegic infusions from 38.0±4.0 to 26.1±3.7 IU/45 ml/g dry weight (P=0.044). In contrast, the inclusion of DMA in the pH 6.6 solution provided no added benefit. (Data are expressed as the mean±SEM.) Conclusions: These results suggest that the lesser efficacy of multidose hypothermic cardioplegia in the neonatal rabbit heart may depend on the pH of the cardioplegic solution and is likely to arise, at least in part, from activation of the Na⁺/H⁺ exchanger.

Key Words: Multidose cardioplegia • Hypothermia • pH • Na⁺/H⁺ exchange • Immature heart