Heparin and Human Lipid Metabolism

Rutstein, David D.; Castelli, W P; Nickerson, RitaJ.

doi:10.1016/s0140-6736(69)91801-7

Cited by 47 publications

(7 citation statements)

References 16 publications

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“…The effective concentrations of FFA found to be depressant in the hypoxic muscles were thus within the clinical range (7,30). Clearly, the influence of high arterial concentrations of FFA on myocardial function in patients with ischemic heart disease warrants further study.…”

Section: Discussionmentioning

confidence: 81%

“…Clinical trials of therapy with glucose and insulin have yielded conflicting results (31-33), but as pointed out by Owen and his colleagues (34), these trials have been directed toward replacement of intracellular potassium (31-33, 35, 36) rather than the maintenance of high arterial concentrations of glucose. The arterial concentrations of FFA were not considered in these studies, but they are known to be raised by catecholamines and by heparin (30,37). If the conclusions drawn from the present study apply to the intact animal, they could have important clinical implications.…”

Section: Discussionmentioning

confidence: 99%

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Depression of Myocardial Contractility in Rats by Free Fatty Acids during Hypoxia

Henderson

Most

Parmley

et al. 1970

Circulation Research

117

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Rat papillary muscles were used to study the influence of glucose (5 HIM), linoleate (1 to 1.75 mMJ, octanoate (0.5 to 1.75 HIM) and pent-4-enoic acid (1 to 5 DIM) on mechanical performance under oxygenated, hypoxic and anoxic conditions. The buffer solution contained 0.3 DIM albumin. Free fatty acids (FFA) (1.0 to 1.75 DIM) did not alter mechanical performance under oxygenated conditions. During hypoxia or anoxia, FFA (0.5 to 1.75 HIM) depressed contractility and increased resting force; glucose improved mechanical performance and modified the depressant effects of FFA. The depressant effect of the nonmetabolized FFA, pentenoic acid, was similar to that of other FFA. This suggests that the effect was mediated directly by FFA or acyl CoA derivatives rather than their metabolic products, and that it might be due to a detergent effect or calcium binding by FFA present in excess of intracellular FFA binding capacity at low pH. Force development during anoxia could be augmented by calcium, implying that the reduced ability of the myofilaments to contract could not be attributed entirely to a reduction of high energy stores. ADDITIONAL KEY WORDSlinoleate octanoate pent-4-enoic acid calcium binding detergent action of free fatty acids optimal oxygen requirement of rat myocardium paired stimulation• It has been demonstrated that glucose improves the mechanical performance and prolongs the survival of anoxic hearts (1-4), but the possible influence of free fatty acids (FFA) under conditions of oxygen deprivation has received little attention. High concentrations of FFA have been shown to increase myocardial oxygen consumption (MV02) in aerobically perfused rat hearts (5) and to cause arrhythmias in dogs with experimentally induced infarction (6). Furthermore, high serum levels of FFA have been correlatedFrom the Cardiovascular Division, Peter Bent

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Depression of Myocardial Contractility in Rats by Free Fatty Acids during Hypoxia

Henderson

Most

Parmley

et al. 1970

Circulation Research

117

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“…Free Fatty AciCUJ and Arrhythmia during Clinical Myocardial Infarction. Tho plasma FFA levels in dogs with arrhythmia after experimental myocardial infarction were far above the levels of plasma FF A which occur clinically [2] except when heparin is given [36]. It could be argued therefore that the toxic effects of these levels in dogs have no analogy in man.…”

Section: One Example Of the Relationship Between Elevation Of Ff A Anmentioning

confidence: 92%

The Role of Free Fatty Acids in the Production of Ventricular Arrhythmias after Acute Coronary Artery Occlusion

1971

Eur J Clin Investigation

182

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After After coronary artery occlusion had been produced in intact dogs, marked elevation of plasma FFA was usually associated with the development of frequent ventricular ectopic systoles and sometimes with ventricular tachycardia or even ventricular fibrillation. These arrhythmias occurred 10–30 min. after the maximum recorded level of FFA.— Elevation of plasma FFA was achieved by inducing plasma lipolysis with heparin. The increased frequency of ventricular ectopic systoles could be reduced and ventricular tachycardia abolished by the administration of protamine sulphate, which has no known anti‐arrhythmic effect on spontaneous arrhythmia, but suppresses heparin‐induced plasma lipolysis.— No haemodynamic changes occurred with the administration of heparin and Intralipid. While infusion of Intralipid and heparin caused reduction in pH of approximately 0.04, evidence is presented that this is not a stimulus for increased arrhythmia.—The administration of noradrenaline to dogs with coronary artery occlusion can also cause arrhythmia even when administered in extremely small doses. The effect is a biphasic one. An immediate initial arrhythmia may occur and is associated with a rise in blood pressure and a reflex bradycardia but not with any significant elevation of FFA. Such arrhythmias disappear when sinus bradycardia is prevented. Arrhythmia can recur during the infusion of nor‐adrenaline in the absence of haemodynamie change and this is associated with marked elevation of plasma FFA. This late arrhythmia can be suppressed or prevented by the administration of a drug which reduces adipose tissue lipolysis.—It is concluded that elevated plasma FFA can have an ar‐rhythmogenic action when there is associated myocardial hypoxia and this effect can be independent of catecholamine activity.

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“…These changes were associated with decreases in the percentage of palmitic and stearic acids. A proportionally greater increase in oleic and linoleic acids has been reported in plasma from uremics, compared with plasma from healthy individuals after addition of heparin in vitro [10], but not with heparin in some in vivo studies [22][23][24],…”

Section: Changes In Individual Nefa During Dialysis With Heparinmentioning

confidence: 99%

Heparin, Fatty Acids and Sodium, Potassium-ATPase Inhibition by Plasma Factors during Hemodialysis

Gault¹,

Vasdev²,

Longerich³

et al. 1992

Nephron

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To assess the relationship between heparin and the associated increase in nonesterified fatty acids (NEFA) and their possible influence on NaK-ATPase during hemodialysis, we studied two groups of patients: (1) 12 patients on chronic hemodialysis dialysed with heparin and (2) 6 patients dialysed without heparin. All 12 patients who received heparin anticoagulation had a 7-fold rise in NEFA on average and also had an increase in circulating inhibitors of NaK-ATPase assayed by ³H-ouabain displacement from NaK-ATPase and/or by effect of plasma on the uptake of ⁸⁶Rb by rat aortic rings. Serial assays in 3 of the patients receiving heparin showed NEFA and inhibitory changes to be at or near maximum within 30-60 min. Of the individual NEFA, the greatest relative increases were in oleic (18:1) and linoleic (18:2) acids, and the strongest correlations were between linoleic acid and both ³H-ouabain displacement (r = 0.94) and ⁸⁶Rb uptake (r=0.86). However, a small and slower increase in NEFA also occurred in 3 of the patients dialysed without heparin. We conclude that heparin anticoagulation during dialysis leads to a rapid and marked increase in circulating NEFA, particularly the unsaturated fatty acids, with a corresponding interference with NaK-ATPase activity. The clinical significance of these findings is unknown. The rise in NEFA during dialysis without heparin in some patients suggests that factors other than heparin may also contribute to the rise in NEFA.

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Heparin and Human Lipid Metabolism

Cited by 47 publications

References 16 publications

Depression of Myocardial Contractility in Rats by Free Fatty Acids during Hypoxia

Depression of Myocardial Contractility in Rats by Free Fatty Acids during Hypoxia

The Role of Free Fatty Acids in the Production of Ventricular Arrhythmias after Acute Coronary Artery Occlusion

Heparin, Fatty Acids and Sodium, Potassium-ATPase Inhibition by Plasma Factors during Hemodialysis

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