Summary
The effect of high- and low-density lipoproteins separated from human serum on the postischemic reperfusion arrhythmias was investigated. The hearts were perfused by working heart mode with Krebs Henseleit bicarbonate buffer containing arachidonic acid (1 μg/ml) for 5 minutes. Whole heart ischemia was induced by the use of a one-way ball valve, and hearts were perfused for 15 minutes followed by 20 minutes of reperfusion. Physiologic concentrations of high- and low-density lipoproteins were constantly infused through the atrial route during ischemic perfusion. Coronary effluent was collected via pulmonary artery cannulation for subsequent radioimmunoassay of thromboxane B2 and 6-keto-prostaglandin F1α, the major stable metabolites of thromboxane A2 and prostacyclin, respectively. The incidence of ventricular arrhythmias during reperfusion was 6/6 (100%), 1/6 (17%), and 6/6 (100%) in control, high-density lipoprotein and low-density lipoprotein infusion groups, respectively. There was no significant difference in coronary flow among the three groups throughout the perfusion. Both thromboxane B2 and 6-keto-prostaglandin F1α increased significantly during ischemia compared with preischemic values in all groups of hearts. However, the ratio of these two parameters varied in control and low-density lipoprotein infusion groups during ischemia, while there was no significant change in the high-density lipoprotein infusion group. These results provide the possibility that arachidonate metabolites may be involved in the regulation of ischemia-reperfusion arrhythmias and that high-density lipoprotein that was infused during ischemia markedly inhibits the incidence of ischemia-reperfusion-induced ventricular arrhythmias, due in part at least, to stabilizing the arachidonate metabolites during ischemic perfusion.
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References
Triau JE, Meydani SN, Schoeffer ES. Oxidized low density lipoprotein stimulates prostacyclin production by adult human vascular endothelial cells. Arteriosclerosis 1988;8: 810–818.
Morel DW, DiCorleto PE, Chisolm GM. Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis 1984;4:357–364.
Cathcart MK, Morel DW, Chisolm GMIII. Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. J Leukocyte Biol 1985;38:341–350.
Parthasarathy S, Wieland E, Steinberg D. A role for endothelial cell lipooxygenase in the oxidative modification of low density lipoprotein. Proc Natl Acad Sci USA 1989;86: 1046–1050.
Manning AS, Hearse DJ. Reperfusion-induced arrhythmias: Mechanism and prevention. J Mol Cell Cardiol 1984;16: 497–518.
Hirsh PD, Hillis LD, Campbell WB, et al. Release of prosta-glandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med 1981;304:685–691.
Lewy RI, Wiener L, Walinsky P, et al. Thromboxane release during pacing-induced angina pectoris: Possible vasoconstrictor influence of the coronary vasculature. Circulation 1988;61:1165–1171.
Edlund A, Sahlin K, Wennmalm Å. Effect of prostacyclin on the severity of ischaemic injury in rabbit hearts subjected to coronary ligation. J Mol Cell Cardiol 1986;18:1067–1076.
Karmazyn M. Contribution of prostaglandins to reperfusion-induced ventricular failure in isolated rat hearts. Am J Physiol 1986;251:H133-H140.
Pomerantz KB, Tall AR, Feinmart SJ, Cannon PJ. Stimulation of vascular smooth muscle cell prostacyclin and prosta-glandin E2 synthesis by plasma high and low density lipoproteins. Circ Res 1984;54:554–565.
Van Sickle WA, Wilcox HG, Malik KU, Nasjletti A. High density lipoprotein-induced cardiac prostacyclin synthesis in vitro: Relationship to cardiac arachidonate mobilization. J Lipid Res 1986;27:517–522.
Spector AA, Scanu AM, Kaduce TL, et al. Effect of human plasma lipoproteins on prostacyclin production by cultured endothelial cells. J Lipid Res 1985;26:288–297.
Schrör K, Kohler P, Müller M, et al. Prostacyclin-thromboxane interactions in the platelet-perfused in vitro heart. Am J Physiol 1981;241:H18-H25.
Havel RJ, Eder H, Bragdon J. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 1955;34:1345–1353.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.
Neely JR, Liebermeister H, Battersby EJ, Morgan HE. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 1967;212:804–814.
Neely JR, Rovetto MT, Whitmer JT, Morgan HE. Effects of ischemia on function and metabolism of the isolated working rat heart. Am J Physiol 1973;225:651–658.
Mochizuki S, Taniguchi M, Seki S, et al. Acid-base changes in ischemic myocardium and intervention with hypothermia or bicarbonate. Jpn Circ J 1988;52:638–645.
Matsuda K, Ushiyama S, Ito T, et al. RS-5186, a novel, long-acting thromboxane synthetase inhibitor. Adv Prosta-glandin Thromboxane Leukotriene Res 1989;19:674–677.
Ushiyama S, Ito T, Asai F, et al. RS-5186, a novel thromboxane synthetase inhibitor with a potent and extended duration of action. Thromb Res 1988;51:507–520.
Nayler WG, Purchase M, Dusting GJ. Effect of prostacyclin infusion during low-flow ischaemia in the isolated perfused rat heart. Basic Res Cardiol 1984;79:125–134.
Robertson RM, Robertson D, Roberts LJ, et al. Thromboxane A2 in vasotonic angina pectoris. N Engl J Med 1981;304:998–1003.
Walinsky P, Smith JB, Lefer AM, et al. Thromboxane A2 in acute myocardial infarction. Am Heart J 1964;108:868–872.
Tada M, Hoshida S, Kuzuya I, et al. Augmented thromboxane A2 generation and efficacy of its blockade in acute myocardial infarction. Int J Cardiol 1985;8:301–312.
Coker SJ, Parratt JR, Ledingham IM, Zeitlin IJ. Thromboxane and prostacyclin release from ischaemic myocardium in relation to arrhythmias. Nature 1981;291:323–324.
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Mochizuki, S., Okumura, M., Tanaka, F. et al. Ischemia-reperfusion arrhythmias and lipids: Effect of human high- and low-density lipoproteins on reperfusion arrhythmias. Cardiovasc Drug Ther 5 (Suppl 2), 269–276 (1991). https://doi.org/10.1007/BF00054748
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DOI: https://doi.org/10.1007/BF00054748