EFFECT OF CATECHOLAMINES ON PHOSPHOLIPASE A2 ACTIVITY

Abstract

S379 INTRODUCTION: Epinephrine (EPI), Norepinephrine (NE) and Dopamine (DA) are commonly used drugs in critical care. While they have well understood pharmacodynamic effects, little is known about the anti- or proinflammatory effect of these substances. Purpose of the study was to establish the anti- or proinflammatory effect of these substances as assessed by the respective effects on PLA2 activity in an in vitro model and to determine the type of activation or inhibition [competitive, un-competitive or noncompetitive (mixed)]. METHODS: 1.) PLA2 (human platelets) was incubated with TRIS-buffer (native) or 1, 10 and 100[micro sign]g of the drugs respectively. PLA2-activity was measured in a radioactive asssay. All values were expressed in % of baseline (BL) values (native activity = 100%). Data were analysed with the Mann-Whitney rank order test. 2.) PLA (2) (porcine) was incubated with different phosphatidyl-choline concentrations and 100[micro sign]g of each drug respectively. Subsequently activity was measured. Lineweaver-Burk representation was used to determine the type of activation/inhibition. RESULTS: (Table 1 and Figure 1)Table 1Figure 1DISCUSSION: High dose EPI, NE and DA activate PLA2. The PLA2 activating effect of the catecholamines while in concordance with the literature was here quantified. The interaction is mixed [enzyme-substrate-activator (ESA) and enzyme-activator (EA) complex formation]. For EPI, NE and DA the physiologic plasma concentrations are in the nmol/l range, while the K values are in the mmol/l range; as such a regulatory function on PLA2 activity can be excluded. Even when ultra high dose iv catecholamine therapy is used, the effect on PLA2 is of no clinical relevance.