Abstract 18453: Morbid Obesity and Metabolic Syndrome in Ossabaw Swine Are Associated with Increased Responsiveness of Platelets to Various Agonists
Introduction: Ossabaw miniature swine develop morbid obesity and metabolic syndrome (MetS) with insulin resistance, hyperlipidemia, hypertension, and atherosclerosis when fed excess calorie atherogenic diet similarly to humans. Hence this swine model seems ideal to study the effect of MetS on platelet reactivity. We hypothesized that higher platelet reactivity in response to various agonists should be displayed in MetS when compared to lean controls.
Methods: We compared 10 morbidly obese Ossabaw pigs that were fed with high caloric/high fat diet for 44 weeks with 10 lean pigs fed regular swine diet. Platelet aggregation was assessed with light transmittance aggregometry using the following agonists at different concentrations in platelet rich plasma; ADP as agonist at concentrations of 0.5 to 20 μM, Arachidonic acid (AA) at 0.5mM and collagen at 1μg/ml. Platelet aggregation was assessed in response to thrombin at concentrations of 0.01 to 0.5 U/ml. Dose response curves and EC50 for ADP and thrombin were calculated using single ligand regression analysis.
Results: Obese pigs with MetS were considerably heavier than lean controls (107.5±8.7 vs. 65.8±6.7 kg, p<0.01), showed elevated BP (148/95 mmHg vs. 126/80 mmHg, p<0.01), and diffuse coronary atherosclerosis. Obese pigs with MetS demonstrated more sustained platelet aggregation in response to collagen than lean pigs (AUC: 286±24 vs. 198±39; p=0.037) and a trend for response to AA (AUC: 260±48 vs. 178±46; p=0.13). Platelets from MetS pigs were more sensitive to ADP-induced platelet aggregation than leans (EC50: 1.83±1.3 vs. 3.64±2.2 μM; p=0.02). A similar trend was observed for thrombin as agonist (EC50: 0.27±0.1 vs. 0.36±0.2 U/ml; p=0.35).
Conclusions: Platelets from Ossabaw pigs with morbid obesity, MetS, and diffuse coronary atherosclerosis exhibit more sustained aggregation when stimulated with collagen and AA when compared to lean controls, which may be related to increased sensitivity of platelets to ADP. These findings are consistent with higher rates of thrombotic events in humans with morbid obesity and MetS. The Ossabaw swine may be an ideal large animal model to study aspects of platelet pathophysiology and vascular devices in a metabolic environment comparable to humans with MetS.
- © 2010 by American Heart Association, Inc.