Heparin’s Endogenous Function, Primarily Anticellular- Destructive, Incidentally Anticoagulant, is Dose-, Source-, and PH-Dependent

Abstract

New experimental findings with heparin used in thermal burns and myocardial infarctions may resolve heparin's historically obscure endogenous function (Saliba and Saliba 1975, Saliba et al. 1976a, b, Saliba and Pavalec 1978). The findings indicate that heparin's endogenous function is primarily anticellular-destructive, incidentally anticoagulant; and that the function is dose-, source-, and ph-dependent. This letter summarizes the findings and the deductions. Historically, small doses of all the heparins from various animal species and tissue sources rapidly prevented intravascular clotting when administered to healthy individuals. For decades, those small conventionally administered doses were used by investigators who did not designate heparin source or dose to have distinctive importance. It was known, but largely ignored, that disease increased anticoagulant dose. Gradually, other effects were discovered, but most experiments who tested heparin's non-anticoagulant properties used the standard anticoagulant doses. Often, those studies produced mixed results and much controversy. Thermal bum and myocardial infarction studies are two examples. Small conventional anticoagulant doses of heparin significantly improved burn pathophy siology in animals without discernible efficacy in humans. Later, larger doses of intestinal mucosa source heparin, administered topically and parenterally, significantly reduced thermal burn extension, edema, fasciectomies, parenteral fluids, skin grafts, and contracture. No patient administered heparin had a bleeding problem. The anticellular-destructive effects were dose-related and dose-dependent (Saliba and Saliba 1975). Because some burns were skin and skeletal muscle infarctions, which histologically resembled myocardial infarctions, heparin was tested in acute myocardial ischemia studies. In dogs, similar large doses of intestinal mucosa heparin significantly reduced the cellulardestructive pathophysiology of myocardial ischemia, improved electrocardiographic recorded S-T segment 84%, reduced myocardial necrosis 32%, and salvaged creatinine phosphokinase 15%. In parallel studies in dogs, as reported in this issue of Thrombosis and Haemostasis, the same large dose of beef lung heparin produced significant, but lesser effects on S-T segment elevations and adenosine triphosphate levels. Reevaluation of conventional anticoagulant doses of intestinal heparin in humans with acute myocardial infarctions produced significant lowering of S-T segment 86 %, without consistent improve ment in cardiac enzyme levels. Based on the evidence to date, the conclusion was that the effects of heparin in myocardial ischemia were both dose and source related and dependent (Saliba et al. 1976 a, b, Saliba and Pavalec 1978). These significant modifications of the two severe cellular-destructive processes, without bleeding problems, indicated that more than anticoagulation was involved. In fact, all known heparin properties and effects were theoretical mechanisms. The list of factors that can mediate cel...