Advertisement

Role of Lipids and Lipid Metabolites in Myocardial Ischaemia

  • Michael Spedding
  • Leslie Patmore
Chapter

Abstract

Elevated levels of free fatty acids (FFA) have long been known to increase susceptibility to arrhythmias and the severity of the damage following myocardial ischaemia (Kurien and Oliver, 1966; de Leiris and Feuvray, 1977; Liedke et al., 1978; Katz and Messineo, 1981; Neely and Feuvray, 1981; Vik-Mo and Mjøs, 1981; Corr et al., 1984; Opie, 1988, Hutter et al., 1990). Dietary factors have marked effects on the severity of arrhythmias and a change in diet to increase the ratio between unsaturated and body saturated fat composition had marked protective effects against ventricular f i brillation and death in a rat model of coronary artery occlusion (Du et al., 1991); the effects were equivalent to pretreatment with antiarrhythmic drugs. The administration of glucose is of benefit in reducing FFA levels and limiting myocardial ischaemia in man, as assessed by inhibition of pacing-induced angina (Thomassen et al., 1989). However, elevated FFA may inhibit glucose oxidation (Renstrom et al., 1990), predominantly at the level of pyruvate dehydrogenase (PDH).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Adams, R. J., Cohen, D. W., Gupte, S., Johnson, J. D., Wallick, E. T., Wang, T. and Schwartz, A. (1979). In vitro effects of palmitylcarnitine on cardiac plasma membrane Na, K-ATPase, and sarcoplasmic reticulum Ca2+-ATPase and Ca2+ transport. J. Biol. Chem., 254,12404–12410PubMedGoogle Scholar
  2. Allely, M. C. and Brown, C. M. (1988). The effects of POCA and TGDA on the ischaemia-induced increase in a -adrenoceptor density in the rat left ventricle. Br. J. Pharmacol., 95, 705 PGoogle Scholar
  3. Allen, D. G. and Orchard, C. H. (1987). Myocardial contractile function during ischemia and hypoxia. Circ. Res., 60, 153–168PubMedCrossRefGoogle Scholar
  4. Bachmann, E., Weber, E. and Zbinden, G. (1983). Biochemical aspects of cardiotoxic effects of a novel type hypoglycemic agent in rats. J. Mot. Cell. Cardiol., 15 (Suppl. 1), 67Google Scholar
  5. Beneking, M., Oellerich, M., Binder, L., Choitz, G.-F. and Haeckel, R. (1990). Inhibition of mitochondrial carnitine acylcarnitine translocase by hypoglycaemia-inducing substances. J. Clin. Chem. Clin. Biochem., 28, 323–327PubMedGoogle Scholar
  6. van Bilsen, M., van der Vusse, G. J., Willemsen, P. H. M., Coumans, W. A., Roemen, T. H. M. and Reneman, R. S. (1989). Lipid alterations in isolated, working rat hearts during ischaemia and reperfusion: its relation to myocardial damage. Circ. Res., 64, 304–314PubMedCrossRefGoogle Scholar
  7. van Bilsen, M. van der Vusse, G. J., Willemsen, P. H. M., Coumans, W. A., Roeme, T. H. M. and Reneman, R. S. (1990). Effects of nicotinic acid and mepacrine on fatty acid accumulation and myocardial damage during ischemia and reperfusion. J. Mot. Cell. Cardiol., 22, 155–163CrossRefGoogle Scholar
  8. Bolli, R., Triana, J. F. and Jeroudi, M. O. (1990). Prolonged impairment of coronary vasodilation after reversible ischemia. Circ. Res., 67, 332–343PubMedCrossRefGoogle Scholar
  9. Brecher, P. (1983). The interaction of long-chain acyl CoA with membranes. Mot. Cell Biochem., 57, 3–15Google Scholar
  10. Chien, K. R., Han, A., Sen, A., Buja, L. M. and Willerson, J. T. (1984). Accumulation of unesterified arachidonic acid in ischemic canine myocardium: Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids. Circ. Res., 54, 313–322PubMedCrossRefGoogle Scholar
  11. Clarke, B., O’Connor, J., Duncan, G. P., Patmore, L. and Spedding, M. (1990). Effects of acyl carnitines on cardiac muscle. J. Mal. Cell. Cardiol., 22 (Suppl. III), S112CrossRefGoogle Scholar
  12. Clarkson, C. W. and Ten Eicke, R. E. (1983). On the mechanism of lysophosphatidylcholine-induced depolarisation of cat ventricular myocardium Circ. Res., 52 543–556PubMedCrossRefGoogle Scholar
  13. Colucci, W. J. and Gandour, R. D. (1988). Carnitine acetyltransferase: a review of its biology, enzymology, and bioorganic chemistry. Bioorganic Chem., 16, 307–334CrossRefGoogle Scholar
  14. Corr, P. B., Creer, M. H., Yamada, K. A., Saffitz, J. E. and Sobel, B. E. (1989). Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation. J. Clin. Invest., 83, 927–936PubMedPubMedCentralCrossRefGoogle Scholar
  15. Corr, P. B., Gross, R. W. and Sobel, B. E. (1984). Amphipathic metabolites and membrane dysfunction in ischemic myocardium. Circ. Res., 55, 135–154PubMedCrossRefGoogle Scholar
  16. Corr, P. B., Saffitz, J. E. and Sobel, B. E. (1987). What is the contribution of altered lipid metabolism to arrhythmogenesis in the ischemic heart? In Hearse, D., Manning, A. and Janse, M. (Eds), Life-threatening Arrhythmias During Ischemia and Infarction. Raven Press, New YorkGoogle Scholar
  17. Corr, P. B., Shayman, J. A., Kramer, J. B. and Kipnis, K. G. (1981a). Increased alpha adrenergic receptors in ischaemic cat myocardium. A potential mediator of electrophysiological derangements. J. Clin. Invest., 67, 1232–1236PubMedPubMedCentralCrossRefGoogle Scholar
  18. Corr, P. B., Snyder, D. W., Cain, M. E., Crafford, Jr., W. A., Gross, R. W. and Sobel, B. E. (1981b). Electrophysiological effects of amphiphiles on canine Purkinje fibers. Implications for dysrhythmia secondary to ischaemia. Circ. Res., 49, 354–363PubMedCrossRefGoogle Scholar
  19. Corr, P. B., Snyder, D. W., Lee, B. I., Gross, R. W., Keim, C. R. and Sobel, B. E. (1982). Pathophysiological concentrations of lysophosphatides and the slow response. Am. J. Physiol., 243, H187–H195PubMedGoogle Scholar
  20. Dainty, I. A., Bigaud, M., McGrath, J. C. and Spedding, M. (1990). Interactions of palmitoyl carnitine with the endothelium in rat aorta. Br. J. Pharmacol., 100, 241–246PubMedPubMedCentralCrossRefGoogle Scholar
  21. Danish Study Group on Verapamil in Myocardial Infarction (1990). The effect of verapamil on mortality and major events after myocardial infarction. The Danish verapamil infarction trial II (DAVIT II). Am. J. Cardiol., 66, 779–785CrossRefGoogle Scholar
  22. Du X. J., Mason, R., Riemersma, R. A. and Winslow, E. (1991). Effects of standard laboratory diets on fatty acid composition and susceptibility to ischaemia-induced arrhythmias in rats. Br. J. Pharmacol., 102, 338PGoogle Scholar
  23. Fink, K. L. and Gross, R. W. (1984). Modulation of canine myocardial sarcolemmal membrane fluidity by amphiphilic compounds. Circ. Res., 55, 585–594PubMedCrossRefGoogle Scholar
  24. Gandour, R. D. (1989). Molecular recognition in carnitine acyltransferases. J. Inc. Phenom. Mol. Rec. Chem., 7, 39–51CrossRefGoogle Scholar
  25. Gandour, R. D., Colucci, W. J. and Fronczeck, F. R. (1985). Crystal structures of carnitine and acetylcarnitine zwitterions: a structural hypothesis for mode of action. Bioorganic Chem., 13, 197–208CrossRefGoogle Scholar
  26. Gandour, R. D., Colucci, W. J., Stelly, T. C., Brady, P. S. and Brady, L. J. (1988). Hemipalmitoylcarnitinium, a strong competitive inhibitor of purified hepatic carnitine palmitoyltransferase. Arch. Biochem. Biophys., 267, 515–520PubMedCrossRefGoogle Scholar
  27. Gross, R. W. and Sobel, B. E. (1983). Rabbit myocardial cytosolic lysophospholipase; purification, characterisation and competitive inhibition by 1-palmitoyl carnitine. J. Biol. Chem., 258, 5221–5226PubMedGoogle Scholar
  28. Heathers, G. P., Yamada, K. A., Kanter, E. M. and Corr, P. B. (1987). Long chain acylcarnitines mediate the hypoxia induced increase in alpha-1 adrenergic receptors on adult canine myocytes. Circ. Res., 61, 735–746PubMedCrossRefGoogle Scholar
  29. Held, P. H., Yusuf, S. and Furberg, C. D. (1989). Calcium channel blockers in acute myocardial infarction and unstable angina: an overview. Br. Med. J., 299, 1187–1192CrossRefGoogle Scholar
  30. Higgins, A. J., Faccini, J. M. and Greaves, P. (1985). Coronary hyperemia and cardiac hypertrophy following inhibition of fatty acid oxidation. Adv. Myocardiol., 6, 329–338PubMedGoogle Scholar
  31. Hutter, J. F., Alves, C. and Soboll, S. (1990). Effects of hypoxia and fatty acids on the distribution of metabolites in rat heart. Biochim. Biophys. Acta, 1016, 244–252PubMedCrossRefGoogle Scholar
  32. Hymel, L., Schindler, H., Inui, M., Fleischer, S., Streissnig, J. and Glossmann, H. (1989). A molecular model of excitation-contraction coupling at the skeletal muscle triad junction via coassociated oligomeric calcium channels. Ann. N.Y. Acad. Sci., 560, 185–188CrossRefGoogle Scholar
  33. Ichihara, K. and Neely, J. R. (1985). Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids. Am. J. Physiol., 249 (Heart Circ. Physiol., 18, H492–H497Google Scholar
  34. Idell-Wenger, J. A., Grotyohann, L. W. and Neely, J. R. (1978). Coenzyme A and carnitine distribution in normal and ischemic hearts. J. Biol. Chem., 253, 4310–4318PubMedGoogle Scholar
  35. Innoue, D. and Pappano, A. J. (1983). L-Palmitylcarnitine and calcium ions act similarly on excitatory ionic currents in avian ventricular muscle. Circ. Res., 52, 625–634CrossRefGoogle Scholar
  36. Katz, A. M. and Messineo, F. C. (1981). Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ. Res., 48, 1–16PubMedCrossRefGoogle Scholar
  37. Kenny, B. A., Fraser, S., Kilpatrick, A. T. and Spedding, M. (1990). Selective antagonism of calcium channel activators by fluspirilene. Br. J. Pharmacol., 100, 211–216PubMedPubMedCentralCrossRefGoogle Scholar
  38. Kim, D. and Duff, R. A. (1990). Regulation of K+ channels in cardiac myocytes by free fatty acids. Circ. Res., 67, 1040–1046PubMedCrossRefGoogle Scholar
  39. Kiorpes, T. C., Hoerr, D., Ho, W., Weaner, L. E., Inman, M. G. and Tutwiler, G. F. (1984). Identification of 2-tetradecylglycidyl coenzyme A as the active form of methyl 2-tetradecylglycidate (methyl palmoxirate) and its characterization as an irreversible, activesite-directed inhibitor of carnitine palmitoyltransferase A in isolated rat liver mitochondria. J. Biol. Chem., 259, 9750–9755PubMedGoogle Scholar
  40. Kiyosue, T. and Arita, M. (1986). Effects of lysophosphatidylcholine on resting potassium conductance of isolated guinea pig ventricular cells. Pflugers Arch., 406, 296–302PubMedCrossRefGoogle Scholar
  41. Knabb, M. T., Saffitz, J. E., Corr, P. B. and Sobel, B. E. (1986). The dependence of electrophysiological derangements on accumulation of endogenous long-chain acyl carnitine in hypoxic neonatal rat myocytes. Circ. Res., 58, 230–240PubMedCrossRefGoogle Scholar
  42. Kobayashi, A., Watanabe, H., Fujisawa, S., Yamamoto, T. and Yamazaki, N. (1989). Effects of L-carnitine and palmitoylcarnitine on membrane fluidity of human erythrocytes. Biochim. Biophys. Acta, 986, 83–88PubMedCrossRefGoogle Scholar
  43. Krause, S. M., Jacobus, W. E. and Becker, L. C. (1989). Alterations in cardiac sarcoplasmic reticulum calcium transport in the postischemic ‘stunned’ myocardium. Circ. Res., 65, 526–530PubMedCrossRefGoogle Scholar
  44. Krutzfeldt, A., Spahr, R., Mertens, S., Siegmund, B. and Piper, H. M. (1990). Metabolism of exogenous substrates by coronary endothelial cells in culture. J. Mol. Cell. Cardiol., 22, 1393–1404PubMedCrossRefGoogle Scholar
  45. Kurien, V. A., and Oliver, M. F., (1966). Serum-free-fatty-acids after acute myocardial infarction and cerebral vascular occlusion. Lancet, ii, 122–127CrossRefGoogle Scholar
  46. Lamers, J. M. J., de Jonge-Stinis, J. T., Verdouw, P. D. and Hulsmann, W. C. (1987). On the possible role of long chain fatty acylcarnitine accumulation in producing functional and calcium permeability changes in membranes during myocardial ischaemia. Cardiovasc. Res., 21, 313–322PubMedCrossRefGoogle Scholar
  47. Lee, S. M., Tutwiler, G., Bressler, R. and Kircher, C. H. (1982). Metabolic control and prevention of nephropathy by 2-tetradecylglycidate in the diabetic mouse (db/db). Diabetes, 31, 12–18PubMedCrossRefGoogle Scholar
  48. de Leiris, J. and Feuvray, D. (1977). Ischaemia-induced damage in the working rat heart preparation: the effect of perfusate substrate composition upon subendocardial ultrastructure of the ischaemic left ventricular wall. J. Mol. Cell. Cardiol., 9, 365–373PubMedCrossRefGoogle Scholar
  49. Liedtke, A. J., Nellis, S. and Neely, J. R. (1978). Effects of excess free fatty acids on mechanical and metabolic function in normal and ischemic myocardium in swine. Circ. Res., 43, 652–661PubMedCrossRefGoogle Scholar
  50. Limbruno, U., Zucchi, R., Ronca-Testoni, S., Galbani, P., Ronca, G. and Mariani, M. (1989). Sarcoplasmic reticulum function in the ‘stunned’ myocardium. J. Mol. Cell. Cardiol., 21, 1063–1072PubMedCrossRefGoogle Scholar
  51. Lopaschuk, G. D. and Spafford, M. (1989). Response of isolated working hearts to fatty acids and carnitine palmitoyltransferase I inhibition during reduction of coronary flow in acutely and chronically diabetic rats. Circ. Res., 65, 378–387PubMedCrossRefGoogle Scholar
  52. Lopaschuk, G. D., Spafford, M. A., Davies, N. J. and Wall, S. R. (1990). Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischaemia. Circ. Res., 66, 546–553PubMedCrossRefGoogle Scholar
  53. Lopaschuk, G. D., Wall, S. R., Olley, P. M. and Davies, N. J. (1988). Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ. Res., 63, 1036–1043PubMedCrossRefGoogle Scholar
  54. Mann, R. Y. K. (1988). Lysophosphatidylcholine-induced arrhythmias and its accumulation in the rat perfused heart. Br. J. Pharmacol., 93, 412–416CrossRefGoogle Scholar
  55. Meszaros, J. and Pappano, A. J. (1990). Electrophysiological effects of L-palmitoylcarnitine in single ventricular myocytes. Am. J. Physiol., 258 (Heart Circ. Physiol., 27), H931–H938PubMedGoogle Scholar
  56. Meszaros, J., Villanova, L., Pappano, A. J. (1988). Calcium ions and 1-palmitoyl carnitine reduce erythrocyte electrophoretic mobility: test of a surface charge hypothesis. J. Mol. Cell. Cardiol., 20, 481–492PubMedCrossRefGoogle Scholar
  57. Murthy, M. S. R., Ramsay, R. R. and Pande, S. V. (1990). Acyl-CoA chain length affects the specificity of various carnitine palmitoyltransferase with respect to carnitine analogues. Biochem. J., 267, 273–276PubMedPubMedCentralCrossRefGoogle Scholar
  58. Nasa, Y., Ichihara, K. and Abiko, Y. (1990). Both d-cis- and I-cis-diltiazem have anti-ischaemic action in the isolated, perfused working rat heart. J. Pharmacol. Exp. Ther., 255, 680–689PubMedGoogle Scholar
  59. Neely, J. R. and Feuvray, D. (1981). Metabolic products and myocardial ischemia. Am. J. Pathol., 102, 282–291PubMedPubMedCentralGoogle Scholar
  60. Neely, J. R. and Morgan, H. E. (1974). Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Ann. Rev. Physiol., 36, 413–459CrossRefGoogle Scholar
  61. Opie, L. H. (1988). Sympathetic stimulation of ischemic myocardium: role of plasma free fatty acids and potassium. J. Cardiovasc. Pharmacol., 12 (Suppl. 1), S31–S38PubMedCrossRefGoogle Scholar
  62. Patmore, L., Anderson, A. J., Duncan, G. P. and Spedding, M. (1990). Actions of palmitoyl carnitine in embryonic chick myocytes. J. Mol. Cell. Cardiol., 22 (Suppl. III), S113CrossRefGoogle Scholar
  63. Patmore, L. and Duncan, G. P. (1988). Effects of calcium channel antagonists and facilitators on beating of primary cultures of embryonic chick heart cells. Br. J. Pharmacol., 95, 771–776PubMedPubMedCentralCrossRefGoogle Scholar
  64. Patmore, L., Duncan, G. P. and Spedding, M. (1989). Interactions of palmitoyl carnitine with calcium-antagonists in myocytes. Br. J. Pharmacol., 97, 443–450PubMedPubMedCentralCrossRefGoogle Scholar
  65. Paulson, D. J., Schmidt, M. J., Romens, J. and Shug, A. L. (1984). Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia: effects of r.-acetylcarnitine. Basic Res. Cardiol., 79, 551–561PubMedCrossRefGoogle Scholar
  66. Pesaturo, J. A. and Gwathmey, J. K. (1990). The role of mitochondria and sarcoplasmic reticulum calcium handling upon reoxygenation of hypoxic myocardium. Circ. Res., 66, 696–709PubMedCrossRefGoogle Scholar
  67. Philipson, K. D. (1984). Interaction of charged amphiphiles with Na+-Ca2+ exchange in cardiac sarcolemmal vesicles. J. Biol. Chem., 259, 13999–14002PubMedGoogle Scholar
  68. Philipson, K. D., Langer, G. A. and Rich, T. L. (1985). Charged amphiphiles regulate heart contractility and sarcolemma-Ca2+ interactions. Am. J. Physiol., 248, H147–H150PubMedGoogle Scholar
  69. Piper, M. H., Sezer, O., Schwartz, P., Hutter, J. F., Schweickhardt, C. and Spieckermann, P. G. (1984). Acyl-carnitine effects on isolated cardiac mitochondria and erythrocytes. Basic. Res. Cardiol., 79, 186–198PubMedCrossRefGoogle Scholar
  70. Pitts, B. J. R., Tate, C. A., van Winkle, W. B., Wood, J. M. and Entman, M. L. (1978). Palmitylcarnitine inhibition of the calcium pump in cardiac sarcoplasmic reticulum: a possible role in myocardial ischemia. Life Sci., 23, 391–402PubMedCrossRefGoogle Scholar
  71. Renstrom, B., Nellis, S. H. and Liedtke, A. J. (1990). Metabolic oxidation of pyruvate and lactate during early myocardial reperfusion. Circ. Res., 66, 282–288PubMedCrossRefGoogle Scholar
  72. Rose, H., Hennecke, T. and Kammermeier, H. (1990). Sarcolemmal fatty acid transfer in isolated cardiomyocytes governed by albumin/membrane-lipid partition. J. Mol. Cell. Cardiol., 22, 883–892PubMedCrossRefGoogle Scholar
  73. Saito, T., Wolf, A., Menon, N. K., Saeed, M. and Bing, R. J. (1988). Lysolecithins as endothelium-dependent vascular smooth muscle relaxants that differ from endothelium-derived relaxing factor (nitric oxide). Proc. Nad Acad. Sci. USA, 85, 8246–8250CrossRefGoogle Scholar
  74. Sawicki, G. J. and Arnsdorf, M. F. (1985). Electrophysiologic actions and interactions between lysophosphatidylcholine and lidocaine in the nonsteady state: the match between multiphasic arrhythmogenic mechanisms and multiple drug effects in cardiac Purkinje fibers. J. Pharmacol. Exp. Ther., 235, 829–839PubMedGoogle Scholar
  75. Seitelberger, R., Huber, S., Schwarzacher, S. and Raberger, G. (1990). Effects of acylcarnitine transferase blockage on metabolism and function in the normally and underperfused canine myocardium. J. Clin. Chem. Clin. Biochem., 28, 341–346PubMedGoogle Scholar
  76. Seitelberger, R., Kraupp, O., Beck, A., Bacher, S. and Raberger, G. (1984). Effects of acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentylj-oxirane-2-carboxylate (POCA) on cardiodynamics and myocardial metabolism in dogs. J. Car-diovasc. Pharmacol., 6, 902–908CrossRefGoogle Scholar
  77. Seitelberger, R., Kraupp, O., Winkler, M., Brugger, G. and Raberger, G. (1985). Effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on metabolism and regional function in the underperfused canine myocardium. J. Cardiovasc. Pharmacol., 7, 273–280PubMedCrossRefGoogle Scholar
  78. Selby, P. L. and Sherratt, H. S. A. (1989). Substituted 2-oxiranecarboxylic acids: a new group of candidate hypoglycaemic drugs. TIPS, 10, 495–500PubMedGoogle Scholar
  79. Sheridan, D. J., Penkoske, P. A., Sobel, B. E. and Corr, P. B. (1980). Alpha adrenergic contributions to dysrhythmia during myocardial ischaemia and reperfusion in cats. J. Clin. Invest., 65, 161–171PubMedPubMedCentralCrossRefGoogle Scholar
  80. Spedding, M. (1985a). Competitive interactions between Bay K 8644 and nifedipine in K+ depolarized smooth muscle: a passive role for Ca2+? Naunyn-Schmiedeberg’s Arch. Pharmacol., 328, 464–466CrossRefGoogle Scholar
  81. Spedding, M. (1985b). Activators and inactivators of Ca+ channels: new perspectives. J. Pharmacol. (Paris), 16, 319–343Google Scholar
  82. Spedding, M. and Berg, C. (1984). Interactions between a ‘calcium channel agonist’ Bay K 8644, and calcium antagonists differentiate calcium antagonist subgroups in K+-depolarized smooth muscle. Naunyn-Schmiedeberg’s Arch. Pharmacol., 328, 69–75CrossRefGoogle Scholar
  83. Spedding, M. and Mir, A. K. (1987). Direct activation of Ca2+ channels by palmitoyl carnitine, a putative endogenous ligand. Br. J. Pharmacol., 92, 457–468PubMedPubMedCentralCrossRefGoogle Scholar
  84. Steenbergen, C. and Jennings, R. B. (1984). Relationship between lysophospholipid accumulation and plasma membrane injury during total in vitro ischemia in dog heart. J. Mol. Cell. Cardiol., 16, 605–621PubMedCrossRefGoogle Scholar
  85. Steenbergen, C., Murphy, E., Levy, L. and London, R. E. (1987). Elevation in cytosolic calcium concentration early in myocardial ischemia in perfused rat heart. Circ. Res., 60, 700–707PubMedCrossRefGoogle Scholar
  86. Takeyama, N., Matsuo, N., Takagi, D. and Tanaka, T. (1989). Determination of overt carnitine palmitoyltransferase by reversed-phase high-performance liquid chromatography. J. Chromatog., 491, 69–76CrossRefGoogle Scholar
  87. Thomassen, A., Nielsen, T. T., Bagger, J. P. and Henningsen, P. (1989). Antianginal and cardiac metabolic effects of low-dose glucose infusion during pacing in patients with and without coronary heart disease. Am. Heart J., 118, 25PubMedCrossRefGoogle Scholar
  88. Ugwu, A. C., McGrath, J. C. and Spedding, M. (1987). Comparison of the effects of palmitoyl carnitine and Bay K 8644 on the calcium-sensitivity of the rat tail artery. Br. J. Pharmacol., 92, 552PGoogle Scholar
  89. Unitt, J. F., McCormack, J. G., Reid, D., MacLachlan, L. K. and England, P. J. (1989). Direct evidence for a role of intramitochondrial Ca2+ in the regulation of oxidative phosphorylation in the stimulated rat heart. Biochem. J., 262, 293–301PubMedPubMedCentralCrossRefGoogle Scholar
  90. Vik-Mo, H. and Mjøs, O. D. (1981). Influence of free fatty acids on myocardial oxygen consumption and ischemic injury. Am. J. Cardiol., 48, 361–365PubMedCrossRefGoogle Scholar
  91. Wagenknecht, T., Grassucci, R., Frank, J., Saito, A., Inui, M. and Fleischer, S. (1989). Three-dimensional architecture of the calcium channel/foot structure of sarcoplasmic reticulum. Nature, 338, 167–170PubMedCrossRefGoogle Scholar
  92. Wise, B. C., Glass, D. B., Chou, C.-H. J., Raynor, R. L., Katoh, N., Schatzman, R. C., Turner, R. S., Kibler, R. F. and Kuo, J. F. (1982). Phospholipid-sensitive Ca2+-dependent protein kinase from heart. II. Substrate specificity and inhibition by various agents. J. Biol. Chem., 257, 8489–8495PubMedGoogle Scholar
  93. Wise, B. C. and Kuo, J. F. (1983). Modes of inhibition by acylcarnitines, adriamycin and trifluoperazine of cardiac phospholipid-sensitive calcium-dependent protein kinase. Biochem. Pharmacol., 32, 1259–1265PubMedCrossRefGoogle Scholar
  94. Yokota, S., Hironaka, Y. and Ohara, N. (1989). Effects of 1-carnitine on membrane potential derangements induced by palmitoylcarnitine and anoxia in isolated superfused guinea-pig papillary muscle. Res. Commun. Chem. Pathol. Pharmacol., 66, 179–190PubMedGoogle Scholar
  95. Zierz, S. and Engel, A. G. (1987). Different sites of inhibition of carnitine palmitoyltrans-ferase by malonyl-CoA, and by acetyl-CoA and CoA, in human skeletal muscle. Biochem. J., 245, 205–209PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Macmillan Publishers Limited 1992

Authors and Affiliations

  • Michael Spedding
  • Leslie Patmore

There are no affiliations available

Personalised recommendations