Circulation Research, Vol 58, 249-256, Copyright © 1986 by American Heart Association

ARTICLES

The combined effects of hypoxia, high K+, and acidosis on the intracellular sodium activity and resting potential in guinea pig papillary muscle

AA Wilde and AG Kleber

Several reports have shown that electrical and ionic changes occurring in acute myocardial ischemia can be closely mimicked by exposure of tissue to hypoxic, acid-, and glucose-free solutions at elevated [K+]o. In the present work, this approach was chosen to distinguish between the combined effects of hypoxia, substrate withdrawal, and acidosis, and the effects of two different levels of [K+]o (4.7 mM and 11.5 mM) on intracellular sodium activity and resting membrane potential. Measurements were made with microelectrodes in isolated guinea pig papillary muscles. In normoxia at 4.7 mM [K+]o, intracellular sodium activity was 7.5 mM (+/- 1.9 mM, SD) during stimulation at 1 Hz. Combined hypoxia, substrate withdrawal, and acidosis increased intracellular sodium activity significantly, by 3-4 mM in 4.7 mM [K+]o and by approximately 2 mM in 11.5 mM [K+]o, after 9-10 minutes. Increasing [K+]o in normoxic solution decreased intracellular sodium activity by 1.9 mM (+/- 1.3 mM, SD). The transition from normal (4.7 mM [K+]o) Tyrode's solution to "ischemic solution" (hypoxia, acidosis, substrate withdrawal, 11.5 mM [K+]o) was associated with a small initial increase and a subsequent decrease of intracellular sodium activity. The steady state level after 12 minutes was not significantly different from the level in normal Tyrode's solution. The secondary decrease of intracellular sodium activity coincided with the gradual development of inexcitability and was absent in quiescent preparations. Combined hypoxia, acidosis, and glucose-withdrawal produced a depolarization by 7-10 mV at 4.7 mM and at 11.5 mM [K+]o, probably reflecting cellular potassium loss and extracellular potassium accumulation in the restricted extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				G.-W. He, Z.-D. Ge, A. P. C. Yim, Q. Yang, and R.-Z. Zhang Electrophysiologic and mechanical evidence of superiority of hyperpolarizing versus depolarizing cardioplegia in protection of endothelium-derived hyperpolarizing factor-mediated endothelial function: A study in coronary resistance arteries J. Thorac. Cardiovasc. Surg., June 1, 2004; 127(6): 1773 - 1780. [Abstract] [Full Text] [PDF]

				B. Rodriguez, J. M. Ferrero Jr., and B. Trenor Mechanistic investigation of extracellular K+ accumulation during acute myocardial ischemia: a simulation study Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H490 - H500. [Abstract] [Full Text] [PDF]

				O. M. Sejersted and G. Sjogaard Dynamics and Consequences of Potassium Shifts in Skeletal Muscle and Heart During Exercise Physiol Rev, October 1, 2000; 80(4): 1411 - 1481. [Abstract] [Full Text] [PDF]

				L.-M. Hung, J.-K. Chen, S.-S. Huang, R.-S. Lee, and M.-J. Su Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes Cardiovasc Res, August 18, 2000; 47(3): 549 - 555. [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]

				F. Brasch, M. Neckel, R. Volkmann, G. Schmidt, G. Hellige, and F. Vetterlein Mapping of capillary flow, cellular redox state, and resting membrane potential in hypoperfused rat myocardium Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H2050 - H2064. [Abstract] [Full Text] [PDF]

				M. Tofukuji, N. Matsuda, C. Dessy, K. G. Morgan, and F. W. Sellke INTRACELLULAR FREE CALCIUM ACCUMULATION IN FERRET VASCULAR SMOOTH MUSCLE DURING CRYSTALLOID AND BLOOD CARDIOPLEGIC INFUSIONS J. Thorac. Cardiovasc. Surg., July 1, 1999; 118(1): 163 - 172. [Abstract] [Full Text] [PDF]