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Eur J Cardiothorac Surg 2004;26:981-987
© 2004 Elsevier Science NL

Enhancement of Na⁺,K⁺-ATPase and Ca²⁺-ATPase activities in multi-cycle ischemic preconditioning in rabbit hearts

Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan

Received 10 January 2004; received in revised form 31 May 2004; accepted 16 June 2004.

^* Corresponding author. Tel.: +81-89-960-5383; fax: +81-89-960-5386
e-mail: yoro{at}hypnos.m.ehime-u.ac.jp

Objective: Ischemic preconditioning (IP) has been shown to attenuate intracellular Na⁺ accumulation and Ca²⁺ overload during ischemia and reperfusion, both of which are closely related to the outcome of myocardial damage. We compared the effects of single- and four-cycle IP in Na⁺,K⁺-activated adenosine 5'-triphosphatase (Na⁺,K⁺-ATPase) and Ca²⁺-activated adenosine 5'-triphosphatase (Ca²⁺-ATPase) activities in in vivo rabbit hearts, correlating these differences to the quality of protection against subsequent ischemia. Methods: The morphological outcome was evaluated in in vivo rabbit hearts subjected to 30 min of coronary occlusion and reperfusion for 180 min by assessing the ratio of infarct volume to risk zone volume. The effects of single- and four-cycle preconditioning ischemia were then examined. Another set of in vivo rabbit hearts was subjected to the measurement of ATPase activities at the conclusion of final preconditioning ischemia and at 60 min after reperfusion following 30 min of ischemia. Results: The infarct volume was reduced by single-cycle IP to 38% of that in the control group. The four-cycle IP further reduced the infarct volume, which was 11% of that in the control group. Na⁺,K⁺-ATPase activity at 60 min after reperfusion in the four-cycle group was increased to 172% of that in the control group (10.8 µmol ADP/h/mg protein), whereas no difference was found in the single-cycle group. On the other hand, Ca²⁺-ATPase activity at the conclusion of IP was increased by single-cycle IP, the value being 255% of that in the control group (4.9 µmol ADP/h/mg protein). The four-cycle IP further increased the activity, and the value was 158% of that in the single-cycle group. Conclusions: Since increases in Na⁺,K⁺-ATPase and Ca²⁺-ATPase activities contribute to the decrease in intracellular Ca²⁺ concentration, the enhancement of these activities by four-cycle IP may be involved in the additional protection.

Key Words: Ca²⁺-pump • Infarction • Na⁺/K⁺-pump • Preconditioning • Sarcolemma

Abbreviations: IP, ischemic preconditioning • ATP, adenosine 5'-triphosphate • ADP, adenosine 5'-diphosphate • Na⁺, K⁺-ATPase, Na⁺, K⁺-activated adenosine 5'-triphosphatase • Ca²⁺-ATPase, Ca²⁺-activated adenosine 5'-triphosphatase • TTC, triphenyl tetrazolium chloride • HPLC, high-performance liquid chromatography

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