Circulation Research, Vol 74, 794-805, Copyright © 1994 by American Heart Association

ARTICLES

Stunned myocardium after rapid correction of acidosis. Increased oxygen cost of contractility and the role of the Na(+)-H+ exchange system

K Hata, T Takasago, A Saeki, T Nishioka and Y Goto
Department of Cardiovascular Dynamics, National Cardiovascular Center, Osaka, Japan.

Left ventricular (LV) contractile dysfunction during acidosis has been reported to be almost reversible in crystalloid-perfused hearts after correction of acidosis. In contrast, we have found that, in blood- perfused hearts, contractile function is paradoxically depressed after correction of acidosis with a transient overshoot of contractility during the recovery of pH. To clarify the mechanism of this phenomenon, we measured the LV contractility index (Emax) and the relation between myocardial oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of the LV total mechanical energy) before and after induction and rapid correction of acidosis by CO2 loading (pH 7.00) and unloading in 13 excised cross-circulated canine hearts. During the rapid correction of acidosis in six control hearts, a severe transient overshoot of Emax (404% of acidosis) occurred. However, after correction of acidosis, Emax and PVA were lower than the preacidosis values by 46% (P < .01) and 44% (P < .01) at the same LV volume. When the preacidosis Emax level was restored by Ca2+ infusion, the VO2 intercept (PVA-independent VO2) of the linear VO2-PVA relation exceeded the control value by 18% (P < .05) with an unchanged slope. In addition, the oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased by 83% (P < .01) after correction of acidosis, indicating that postacidosis myocardium requires higher VO2 for nonmechanical activities for a unit increase in Emax. Then, we hypothesized that these mechanoenergetic disorders after rapid correction of acidosis would result from Ca2+ overload via accelerated Na(+)-Ca2+ exchange due to the heavily operating Na(+)-H+ exchange system at the time of rapid pH recovery. To examine this hypothesis, dimethylamiloride, a selective Na(+)-H+ exchange inhibitor, was administered just before the correction of acidosis in the other seven hearts. The administration of dimethylamiloride completely prevented both the mechanical and energetic disorders after correction of acidosis. We conclude that rapid recovery of pH paradoxically depresses myocardial contractility and increases the oxygen cost of contractility through an activation of the Na(+)-H+ exchange system.

This article has been cited by other articles:

				T. Tsuji, F. del Monte, Y. Yoshikawa, T. Abe, J. Shimizu, C. Nakajima-Takenaka, S. Taniguchi, R. J. Hajjar, and M. Takaki Rescue of Ca2+ overload-induced left ventriclur dysfunction by targeted ablation of phospholamban Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H310 - H317. [Abstract] [Full Text] [PDF]

				R. Saeedi, M. Grist, R. B. Wambolt, A. Bescond-Jacquet, A. Lucien, and M. F. Allard Trimetazidine Normalizes Postischemic Function of Hypertrophied Rat Hearts J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 446 - 454. [Abstract] [Full Text] [PDF]

				Q. Liu, J. C. Docherty, J. C. T. Rendell, A. S. Clanachan, and G. D. Lopaschuk High levels of fatty acids delay the recoveryof intracellular pH and cardiac efficiency inpost-ischemic hearts by inhibiting glucose oxidation J. Am. Coll. Cardiol., February 20, 2002; 39(4): 718 - 725. [Abstract] [Full Text] [PDF]

				T. Tsuji, Y. Ohga, Y. Yoshikawa, S. Sakata, T. Abe, N. Tabayashi, S. Kobayashi, H. Kohzuki, K.-I. Yoshida, H. Suga, et al. Rat cardiac contractile dysfunction induced by Ca2+ overload: possible link to the proteolysis of {alpha}-fodrin Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1286 - H1294. [Abstract] [Full Text] [PDF]

				H. Kohzuki, H. Misawa, S. Sakata, Y. Ohga, and M. Takaki Sustained high O2 use for Ca2+ handling in rat ventricular slices under decreased free shortening after ryanodine Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H566 - H572. [Abstract] [Full Text] [PDF]

				M. Taniguchi, C. Wilson, C. A. Hunter, D. J. Pehowich, A. S. Clanachan, and G. D. Lopaschuk Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1762 - H1769. [Abstract] [Full Text] [PDF]

				A. Saeki, Y. Goto, K. Hata, T. Takasago, T. Nishioka, and H. Suga Negative inotropism of hyperthermia increases oxygen cost of contractility in canine hearts Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2855 - H2864. [Abstract] [Full Text] [PDF]

				Y.-I. L. Kim, P. Herijgers, S. K. Laycock, A. Van Lommel, E. Verbeken, and W. J. Flameng Na+/H+ exchange inhibition improves long-term myocardial preservation Ann. Thorac. Surg., August 1, 1998; 66(2): 436 - 442. [Abstract] [Full Text] [PDF]

				O. Frohlich and M. Karmazyn The Na-H exchanger revisited: an update on Na-H exchange regulation and the role of the exchanger in hypertension and cardiac function in health and disease Cardiovasc Res, November 1, 1997; 36(2): 138 - 148. [Full Text] [PDF]

				K. Przyklenk, K. Hata, and R. A. Kloner Is Calcium a Mediator of Infarct Size Reduction With Preconditioning in Canine Myocardium? Circulation, August 19, 1997; 96(4): 1305 - 1312. [Abstract] [Full Text]

				M. F. Allard, S. L. Henning, R. B. Wambolt, S. R. Granleese, D. R. English, and G. D. Lopaschuk Glycogen Metabolism in the Aerobic Hypertrophied Rat Heart Circulation, July 15, 1997; 96(2): 676 - 682. [Abstract] [Full Text]

				B. Liu, A. S. Clanachan, R. Schulz, and G. D. Lopaschuk Cardiac Efficiency Is Improved After Ischemia by Altering Both the Source and Fate of Protons Circ. Res., November 1, 1996; 79(5): 940 - 948. [Abstract] [Full Text]

				B. O. Schonekess, M. F. Allard, and G. D. Lopaschuk Propionyl L-Carnitine Improvement of Hypertrophied Heart Function Is Accompanied by an Increase in Carbohydrate Oxidation Circ. Res., October 1, 1995; 77(4): 726 - 734. [Abstract] [Full Text]