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Abstract

THE possibility that heparin or related chemical substances might be concerned in the transport of fat in the body was suggested by a chance observation made by Hahn in 1943. He noticed that when dogs with a gross alimentary lipwemia were transfused with blood containing heparin as the anticoagulant, samples of plasma withdrawn one to five minutes after the transfusion were completely clear. Hahn found that this clearing of alimentary lipaemia also occurred when animals were given intravenous injections of heparin; it did not occur when heparin was mixed with lipsemic plasma in vitro. Later, Anderson and Fawcett [1950] found that a clearing effect could be produced in vitro when plasma from an animal previously injected with heparin (heparinized plasma) was mixed with lipaemic plasma. These two phenomena, described as the heparin clearing reaction in vivo and in vitro have been confirmed in many animal species including birds and reptiles. The purpose of this review is to describe the investigation of these phenomena and to discuss their possible significance in fat transport. The reaction in vitro has received the most attention and will be discussed first. The events which occur in the lipaemic animal following the injection of heparin can then be considered in relation to the findings in vitro. THE HEPARIN CLEARING REACTION IN VITRO The Mechanism of ClearingThe turbidity of the plasma in alimentary lipawmia is due to the presence of large numbers of visible lipid particles of varying size. They include the chylomicra and a variety of low density lipoprotein complexes. These particles are composed primarily of triglyceride but also contain varying amounts of protein, phosphatide and cholesterol [Laurell, 1954;Robinson, 1955;Lindgren, Nichols and Freeman, 1955;Havel, Eder and Bragdon, 1955]. The experiments of Anderson and Fawcett [1950] showed that, following heparin injection, plasma contained a component, the so-called clearing factor, which had the property of changing these lipid complexes so that they no longer interfered with the transmission of light. This clearing property of heparinized plasma can be demonstrated in vitro in a number of ways: by mixing heparinized plasma with lipaemic plasma [Anderson and Fawcett, 1950], or by adding fatty chyle or isolated turbid lipoproteins to heparinized plasma [French, Robinson and Florey, 1953; Brown, Boyle 151