(Circulation. 1997;96:599-604.)
© 1997 American Heart Association, Inc.
Articles |
Inhibition of Sarcolemmal Na+,K+-ATPase Activity Reduces the Infarct Size–Limiting Effect of Preconditioning in Rabbit Hearts
From the Third Division, Department of Internal Medicine, Kyoto University Hospital, Kyoto, Japan.
Correspondence to Tomoyuki Murakami, MD, Third Division, Department of Internal Medicine, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.
Background The inhibition of sarcolemmal Na+,K+-ATPase activity is closely related to ischemic myocardial cell injury. However, the involvement of this enzyme in preconditioning has not been determined.
Methods and Results We assessed the effect of ischemia on sarcolemmal Na+,K+-ATPase activity. Control and preconditioned rabbits were subjected to 0, 10, 20, 30, and 60 minutes of coronary occlusion. Ten to 60 minutes of ischemia reduced Na+,K+-ATPase activity, whereas preconditioning preserved the activity of this enzyme only during the first 20 minutes of ischemia. To determine whether the preservation of Na+,K+-ATPase activity in the early phase of ischemia contributed to limiting the infarct size, additional rabbits underwent 30 minutes of occlusion followed by 3 hours of reperfusion with or without pretreatment with digoxin, an inhibitor of Na+,K+-ATPase. Infarct size in animals pretreated with digoxin in the absence of preconditioning did not differ from that in controls. It was markedly reduced by preconditioning, whereas digoxin reduced the infarct size–limiting effect. Moreover, preconditioning increased sarcolemmal Na+-Ca2+ exchange activity in rabbits subjected to 20 minutes of ischemia, whereas digoxin diminished this increase.
Conclusions Preconditioning preserves the ischemia-induced reduction in sarcolemmal Na+,K+-ATPase activity in the early phase of ischemia in rabbit hearts. Inhibition of Na+,K+-ATPase activity reduces the infarct size–limiting effect of preconditioning with a loss of increased Na+-Ca2+ exchange activity, implying that this preservation is responsible for the cardioprotective effect of preconditioning.
Key Words: ischemia • preconditioning • sodium • potassium • calcium
This article has been cited by other articles:
 |
|
 |
|
  D. Garcia-Dorado, A. Rodriguez-Sinovas, M. Ruiz-Meana, J. Inserte, L. Agullo, and A. Cabestrero The end-effectors of preconditioning protection against myocardial cell death secondary to ischemia-reperfusion Cardiovasc Res, May 1, 2006; 70(2): 274 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Inserte, D. Garcia-Dorado, V. Hernando, I. Barba, and J. Soler-Soler Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion Cardiovasc Res, May 1, 2006; 70(2): 364 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Inserte, D. Garcia-Dorado, V. Hernando, and J. Soler-Soler Calpain-Mediated Impairment of Na+/K+-ATPase Activity During Early Reperfusion Contributes to Cell Death After Myocardial Ischemia Circ. Res., September 2, 2005; 97(5): 465 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yorozuya, N. Adachi, K. Dote, K. Nakanishi, Y. Takasaki, and T. Arai Enhancement of Na+,K+-ATPase and Ca2+-ATPase activities in multi-cycle ischemic preconditioning in rabbit hearts Eur. J. Cardiothorac. Surg., November 1, 2004; 26(5): 981 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Gross and J. N. Peart KATP channels and myocardial preconditioning: an update Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H921 - H930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Elmoselhi, A. Lukas, P. Ostadal, and N. S. Dhalla Preconditioning attenuates ischemia-reperfusion-induced remodeling of Na+-K+-ATPase in hearts Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1055 - H1063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kevelaitis, A. Oubenaissa, C. Mouas, J. Peynet, and P. Menasche Ischemic preconditioning with opening of mitochondrial adenosine triphosphate-sensitive potassium channels or Na+/H+ exchange inhibition: Which is the best protective strategy for heart transplants? J. Thorac. Cardiovasc. Surg., January 1, 2001; 121(1): 0155 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.W.T Fiolet and A Baartscheer Cellular calcium homeostasis during ischemia; a thermodynamic approach Cardiovasc Res, January 1, 2000; 45(1): 100 - 106. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kevelaitis, A. Oubenaissa, J. Peynet, C. Mouas, and P. Menasche Preconditioning by Mitochondrial ATP-Sensitive Potassium Channel Openers : An Effective Approach for Improving the Preservation of Heart Transplants Circulation, November 9, 1999; 100 (2009): II-345 - II-350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Perrault and P. Menasche Preconditioning: can nature’s shield be raised against surgical ischemic-reperfusion injury? Ann. Thorac. Surg., November 1, 1999; 68(5): 1988 - 1994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Lundmark, R. Ramasamy, P. R. Vulliet, and S. Schaefer Chelerythrine increases Na-K-ATPase activity and limits ischemic injury in isolated rat hearts Am J Physiol Heart Circ Physiol, September 1, 1999; 277(3): H999 - H1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kevelaitis, J. Peynet, C. Mouas, J.-M. Launay, and P. Menasche Opening of Potassium Channels : The Common Cardioprotective Link Between Preconditioning and Natural Hibernation? Circulation, June 15, 1999; 99(23): 3079 - 3085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Haruna, M. Horie, I. Kouchi, R. Nawada, K. Tsuchiya, M. Akao, H. Otani, T. Murakami, and S. Sasayama Coordinate Interaction Between ATP-Sensitive K+ Channel and Na+,K+-ATPase Modulates Ischemic Preconditioning Circulation, December 22, 1998; 98(25): 2905 - 2910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Imahashi, T. Nishimura, J. Yoshioka, and H. Kusuoka Role of Intracellular Na+ Kinetics in Preconditioned Rat Heart Circ. Res., June 8, 2001; 88(11): 1176 - 1182. [Abstract] [Full Text] [PDF]
|
|