430 V. BLOOD LIPIDS 



confirmed the fact that heparin induced a reorientation of blood lipo- 

 proteins, so that the concentrations of cholesterol-bearing S f 12-20 and S f 

 20-100 are markedly reduced. However, plasma cholesterol levels were 

 unaffected by the exogenous heparin, in vivo. On the other hand, adeno- 

 sine-5-monophosphate caused a reduction of the concentrations in the 

 plasma and aorta of chickens, without producing significant changes in the 

 levels of the several lipoproteins. The effects of heparin and AMP were 

 shown to be additive, in normal and in hyperlipoproteinemic rabbits. 459 



In addition to the clearing of turbidity and the redistribution of lipo- 

 proteins, heparin causes a lipolysis. Shore et a/. 461 noted that when plasma, 

 from human subjects who had received intravenous heparin a short time 

 before the sample was withdrawn, was incubated with certain lipoproteins 

 for four to eight hours at 37 °C, a partial hydrolysis of the glyceride com- 

 ponent occurred, with a concomitant release of fatty acids. Brown and 

 co-workers 445 also noted the appearance of fatty acids after clearing, 

 which produced turbidity due to the formation of calcium soaps. These 

 workers presented evidence that the plasma esterases are responsible for 

 the formation of the fatty acids. 



The clearing factor produced by the injection of heparin was found by 

 Spitzer 440 to be dialyzable. It occurs in the albumin fraction. It is in- 

 activated irreversibly at 49 °C. but its action is not affected by thrombin 

 or by thromboplastin. The smallest concentration of heparin which was 

 found to be active was 0.5 Mg-/rnl. The effect of a dosage of 2 mg. lasted 

 forty-five to sixty minutes in a rabbit. Levy and Swank 447 reported that 

 the injection of dextran (molecular weight = 75,000) into dogs produced 

 a marked clearing of a heavy alimentary lipemia in the absence of heparin 

 activity. The explanation for this effect is not immediately apparent. 



b. The Effect of Protamine. Heparin and protamine have been shown 

 to have antagonistic effects. Brown 462463 was the first to observe that the 

 effect of heparin in abolishing lipemia can be counteracted by the adminis- 

 tration of protamine. He also proved that the total amount of serum fatty 

 acids, as well as the visible alimentary lipemia, could be increased by the 

 administration of protamine, even when heparin had not previously been 

 injected. However, it failed to influence the endogenous lipemia of preg- 

 nancy. Spitzer 437,464 reported that protamine was effective only in vivo. 

 Moreover, it failed to influence the fat content in control, fasting rats. 464 



461 B. Shore, A. V. Nichols, and N. K. Freeman, Proc. Soc. Exptl. Biol Med., 83, 216- 

 220(1953). 



462 W. D. Brown, Proc. XVIII Intern. Physiol. Congr., Copenhagen, 1950. 



463 W. D. Brown, Quart. J. Exptl. Physiol, 87, 75-84, 119-129, 215-219 (1952). 



464 J. J. Spitzer, Federation Proc, 12, 137 (1953). 



