Abstract
The effect of asphyxia and subsequent resumption of respiration on the content of adenine nucleotides and some amino acids in heart tissue and mitochondria, as well as respiration of heart mitochondria was studied in rats. The depression of cardiac contractile function during asphyxia showed a better correlation with losses in mitochondrial adenine nucleotides (ATP+ADP+AMP) than those in cardiac tissue. The decrease in the heart work index was accompanied by a decrease in state 3 respiration with glutamate and malate as well as uncoupled respiration with these substrates. This did not occur with succinate. Nonphosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by asphyxia, when respiratory substrates of both types were used. The decreased level of glutamic acid in the tissue and mitochondria of asphyxic hearts was simultaneously observed with a significant increase of alanine in cardiac tissue and of aspartic acid in the mitochondria. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during asphyxia were associated with a reduction of glutamic acid level in mitochondria. The recovery of cardiac function during resumption of respiration was related to the restoration of mitochondrial respiration supported by glutamate and malate, as well as to the restoration of mitochondrial adenine nucleotides and glutamic acid. The results suggest that the depression of cardiac function caused by acute respiratory hypoxia may be attributed to impairment of electron transport, particularly in complex I of the respiratory chain and changes in metabolism of glutamic acid.
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Asimakis GK, Conti VR (1984) Myocardial ischemia: correlation of mitochondrial adenine nucleotide and respiratory function. J Mol Cell Cardiol 16:439–448
Asimakis GK, Conti VR (1985) Phosphate-induced efflux of adenine nucleotides from heart mitochondria. Am J Physiol 249:H1009–1016
Bittl J, Shine KI (1983) Protection of ischemic rabbit myocardium by glutamic acid. Am J Physiol 245:H406–412
Feinstein MB (1962) Effects of experimental congestive heart failure, ouabain and asphyxia on the high-energy phosphate and creatine content of the guinea pig heart. Circ Res 10:333–346
Freminet A (1981) Carbohydrate and amino acid metabolism during acute hypoxia in rats: blood and heart metabolites. Comp Biochem Physiol 70B:427–433
Hearse DJ (1979) Oxygen deprivation and early myocardial contractile failure: a reassessment of the possible role of adenosine triphosphate. Am J Cardiol 44:1115–1121
Hendrickx HHL, Rao GR, Safar P, Gilsvold SE (1984) Asphyxia, cardiac arrest and resuscitation in rats. 1. Short term recovery. Resuscitation 12:97–116
Jennings RB, Kaltenbach JP, Smethers GW (1957) Enzymatic changes in acute myocardial ischemic injury. Arch Pathol 64:10–16
Kauppinen RA, Hiltunen JK, Hassinen IE (1983) Mitochondrial membrane potential, transmembrane difference in NAD+ redox potential and the equilibrium of the glutamate-aspartate translocase in the isolated perfused rat heart. Biochim Biophys Acta 725:425–433
Klein HH, Schaper J, Puschmann, St, Nienaber Ch, Kreuzer H, Shaper W (1981) Loss of canine myocardial nicotinamide adenine dinucleotides determines the transition from reversible to irreversible ischemic, damage of myocardial cells. Basic Res Cardiol 76:612–621
La Noue KF, Walajtys EI, Williamson JR (1973) Regulation of glutamate metabolism and interactions with the citric acid cycle in rat heart mitochondria. J Biol Chem 248:7171–7183
La Noue KF, Watts JA, Koch CP (1981) Adenine nucleotide transport during cardiac ischemia. Am J Physiol 241:H663–671
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurements with the Folin phenol reagent. J Biol Chem 193:265–275
Pisarenko OI, Solomatina ES, Studneva IM, Ivanov VE, Kapelko VI, Smirnov VN (1983) Effect of glutamic and aspartic acids on adenine nucleotides, nitrogen compounds and contractile function during underperfusion of isolated rat heart. J Mol Cell Cardiol 15:53–60
Pisarenko OI, Solomatina ES, Ivanov VE, Studneva IM, Kapelko VI, Smirnov VN (1985) On the mechanism of enhanced ATP formation in hypoxic myocardium caused by glutamic acid. Basic Res Cardiol 80:126–134
Pisarenko OI, Lepilin MG, Ivanov VE (1968) Cardiac metabolism and performance duringl-glutamic acid infusion in postoperative cardiac failure. Clin Sci 70:7–12
Rouslin W, Millard RW (1980) Canine myocardial ischemia: Defect in mitochondrial electron transfer complex. I. J Mol Cell Cardiol 12:639–645
Sanborn T, Gavis W, Berkowitz S, Perrille T, Lesch M (1979) Augmented convertion of aspartate and glutamate to succinate during anoxia in rabbit heart. Am J Physiol 273:H535–541
Shertzer HG, Cascarano J (1979) Anaerobic rat heart: mitochondrial role in calcium uptake and contractility. J Exp Zool 207:337–350
Sordahl LA, Stewart ML (1980) Mechanism(s) of altered mitochondrial calcium transport in acutely ischemic canine hearts. Circ Res 47:814–820
Stoner CD, Sirak HD (1973) Adenine nucleotide-induced contraction of the inner, mitochondrial membrane. J Cell Biol 56:51–64
Taegtmeyer H (1978) Metabolic response to cardiac hypoxia. Increased production of succinate by rabbit papillary muscle. Circ Res 43:808–815
Wachstein M, Meisel E (1955) Succinic dehydrogenase activity in myocardial infarction and in induced myocardial necrosis. Am J Pathol 31:353–365
Williamson JR, Corkey BE (1969) Assays of intermediates of the citric compounds by fluorometric enzyme methods. In: Lowenstein JM (ed) Methods in enzymology, vol XII. Academic Press, New York, pp 488–496
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Pisarenko, O.I., Solomatina, E.S., Studneva, I.M. et al. The relationship between the cardiac contractile function, adenine nucleotides and amino acids of cardiac tissue and mitochondria at acute respiratory hypoxia. Pflugers Arch. 409, 169–174 (1987). https://doi.org/10.1007/BF00584767
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DOI: https://doi.org/10.1007/BF00584767