Circulation Research, Vol 71, 106-119, Copyright © 1992 by American Heart Association

ARTICLES

Subcellular electrolyte alterations during progressive hypoxia and following reoxygenation in isolated neonatal rat ventricular myocytes

FT Thandroyen, D Bellotto, A Katayama, HK Hagler, JT Willerson and LM Buja
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.

This study characterizes the sequential alterations of, and relations between, multiple electrolytes in cytoplasm, mitochondria, and whole cells during hypoxia and on reoxygenation in isolated neonatal rat ventricular myocytes. Subcellular electrolyte content and distribution were measured by electron probe x-ray microanalysis, membrane phospholipid degradation by tritiated arachidonic acid release, and cell morphology by electron microscopy. At 1-2 hours of hypoxia, the myocyte population showed a loss of cytoplasmic potassium, magnesium, and chlorine without alteration of cytoplasmic sodium or calcium. Mitochondria showed increased potassium with unchanged magnesium content. There was no morphological evidence of cell injury or tritiated arachidonic acid release. At 3-5 hours of hypoxia, the myocyte population showed a further loss of cytoplasmic potassium and magnesium and an increase in cytoplasmic sodium, chlorine, and calcium. At a single-cell level, the increase in cytoplasmic sodium preceded the increase in cytoplasmic calcium. Mitochondria showed increased sodium and chlorine and decreased magnesium before increased calcium content; potassium loss was manifest only at 5 hours of hypoxia. At 3-5 hours of hypoxia, there was also tritiated arachidonic acid release and morphological evidence of cell injury. Reoxygenation for 1 hour after 5 hours of hypoxia partially reversed the mean alterations of all electrolytes, except calcium, in the cytoplasm of the myocyte population, whereas analysis was required at a single-cell level to show a partial reversal in calcium levels in cytoplasm of reoxygenated cells. Reoxygenation for 1 hour after 5 hours of hypoxia partially reversed the mean alterations of all electrolytes, including calcium, in the mitochondria of the myocyte population. Recovery of potassium in the cytoplasm correlated with reduction of mitochondrial calcium content on reoxygenation and best predicted recovery of cellular homeostasis of sodium, chlorine, magnesium, and calcium. This study demonstrates that in this experimental model of hypoxia 1) initial losses of cytoplasmic potassium and magnesium occur in the absence of cell injury; 2) increases of sodium, chlorine, and calcium occur in association with cell injury, with sodium increasing before calcium; 3) membrane phospholipid degradation and electrolyte derangement, including increased calcium, may contribute to reversible and irreversible phases of cell injury; 4) analysis of calcium at a subcompartmental level and at a single-cell level is required to correlate reduction of calcium on reoxygenation with recovery of cell homeostasis; 5) reduction of calcium content in mitochondria may predict recovery of cell homeostasis; and 6) recovery of potassium on reoxygenation best predicts recovery of cell membrane function and cell homeostasis.

This article has been cited by other articles:

				W. G. Rehwald, D. S. Fieno, E.-L. Chen, R. J. Kim, and R. M. Judd Myocardial Magnetic Resonance Imaging Contrast Agent Concentrations After Reversible and Irreversible Ischemic Injury Circulation, January 15, 2002; 105(2): 224 - 229. [Abstract] [Full Text] [PDF]

				A. Arutunyan, D. R. Webster, L. M. Swift, and N. Sarvazyan Localized injury in cardiomyocyte network: a new experimental model of ischemia-reperfusion arrhythmias Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1905 - H1915. [Abstract] [Full Text] [PDF]

				J. A. Simpson, J. E. van Eyk, and S. Iscoe Hypoxemia-induced modification of troponin I and T in canine diaphragm J Appl Physiol, February 1, 2000; 88(2): 753 - 760. [Abstract] [Full Text] [PDF]

				R. J. Kim, R. M. Judd, E.-L. Chen, D. S. Fieno, T. B. Parrish, and J. A. C. Lima Relationship of Elevated 23Na Magnetic Resonance Image Intensity to Infarct Size After Acute Reperfused Myocardial Infarction Circulation, July 13, 1999; 100(2): 185 - 192. [Abstract] [Full Text] [PDF]

				M. C.P. Haigney, B. Silver, E. Tanglao, H. S. Silverman, J. D. Hill, E. Shapiro, G. Gerstenblith, and S. P. Schulman Noninvasive Measurement of Tissue Magnesium and Correlation With Cardiac Levels Circulation, October 15, 1995; 92(8): 2190 - 2197. [Abstract] [Full Text]

				A. P. Levy, N. S. Levy, J. Loscalzo, A. Calderone, N. Takahashi, K.-T. Yeo, G. Koren, W. S. Colucci, and M. A. Goldberg Regulation of Vascular Endothelial Growth Factor in Cardiac Myocytes Circ. Res., May 1, 1995; 76(5): 758 - 766. [Abstract] [Full Text]