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Ann Thorac Surg 2002;73:1253-1259
© 2002 The Society of Thoracic Surgeons
a Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong, China
b Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
Accepted for publication December 18, 2001.
* Address reprint requests to Dr Wong, Department of Physiology, University of Hong Kong, 4/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Rd, Hong Kong SAR, China
e-mail: wongtakm{at}hkucc.hku.hk
Bacground. Aprikalim, an adenosine triphosphate (ATP) sensitive K+ (KATP) channel opener, attenuates the elevation of intracellular Ca2+ concentration ([Ca2+]i) and improves the contractile functions after hyperkalemic and hypothermic cardioplegia. There is evidence that cardioplegia increases the Na+-Ca2+ exchange activity without affecting Ca2+ influx through L-type Ca2+ channels or Ca2+ content in the sarcoplasmic reticulum, the intracellular Ca2+ store.
Methods. We measured the Na+-Ca2+ exchange outward current with the patch-clamp technique in single rat ventricular myocytes exposed to hyperkalemia and hypothermia in the presence of aprikalim. The intracellular calcium concentration ([Ca2+]i) during cardioplegia, and the contractile function and [Ca2+]i transients induced by electrical stimulation or caffeine during rewarming and reperfusion in single ventricular myocytes were also determined. Contraction and [Ca2+]i were determined with video tracking and spectrofluorometry, respectively.
Results. Aprikalim, 100 µmol/L, the effect of which was blocked by glibamclamide, a KATP inhibitor, significantly attenuated the hyperkalemia-elevated Na+-Ca2+ exchange current by 26% and 11% at 22°C and 4°C, respectively. Aprikalim also attenuated significantly the [Ca2+]i elevated during cardioplegia. Furthermore aprikalim significantly attenuated the reduction in amplitude and prolongation in duration of contraction of myocytes after cardioplegia. The effects of aprikalim mimicked those of nickle (Ni2+), a Na+-Ca2+ exchange blocker. The electrically or caffeine-induced [Ca2+]i transients were unaltered by cardioplegia or aprikalim.
Conclusions. Aprikalim attenuates the Na+-Ca2+ exchange outward current elevated by hyperkalemia, which may attenuate the [Ca2+]i elevation during hyperkalemia and improve the contractile function after cardioplegia in the ventricular myocyte. The study provides further support that addition of a KATP channel opener to the cardioplegic solution may produce beneficial effects in open heart surgery.
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