The effect of heparin infusion on plasma triglyceride in vivo and in vitro with a method for calculating triglyceride turnover.

Abstract

Abstract Heparin was used to study triglyceride (TG) metabolism by its induction of circulating lipolytic activity. During a constant intravenous infusion of heparin, plasma free fatty acids (FFA) reached new steady elevated levels and plasma TG had new steady lower levels. At this new steady state FFA turnover rates during infusion were calculated from measurement of the lipolytic rate in vitro at pH 7.4 without added substrate with the assumption that all additional FFA arose from plasma TG. In subjects with endogenous lipemia on fat-free diets, FFA turnover was similar to that reported by others using C 14 -palmitate. Partial glyceride accumulation was minimal in vivo and in vitro. Evidence is presented to suggest displacement of the normal TG removal mechanism into plasma by large doses of heparin and virtually complete hydrolysis of triglyceride by the postheparin plasma enzyme. With these assumptions, minimal TG turnover rates during the period of heparin infusion were calculated. There was a significant correlation between turnover rate during heparin infusion and preheparin TG concentration in 10 subjects with endogenous lipemia (TG levels ranging from 67.5 to 955 mg. per 100 ml.). Four other subjects with independent evidence for exogenous lipemia all had turnover rates consistent with a removal defect. Treatment with insulin in 2 severely diabetic subjects increased fractional removal rate of TG and lowered plasma TG to levels compatible with restoration of normal removal capacity. Six other subjects had circulating dietary fat particles and dietary responses suggestive of exogenous lipemia but normal lipolytic responses to heparin as measured with a coconut oil substrate (PHLA). In these subjects TG turnover during heparin was consistent with a primary removal defect unrelated to insulin deficiency. It is concluded that measurement of TG turnover rate during heparin infusion by this nonradioactive method is a useful tool for the evaluation of hypertriglyceridemic states in man.