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Failure of Antiplatelet Treatment in Dietary Atherosclerosis

A Serial Intervention Study
  • Ralph G. DePalma
  • Errol M. Bellon
  • P. M. Manalo
  • Richard A. Bomberger
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Rhesus monkeys fed a diet of sucrose, egg yolk, and 0.5% cholesterol become hyperlipidemic and develop atherosclerotic plaques. Methods to estimate disease severity in seriatim in this model have been described in previous publications. Since it is believed that platelets secrete factors accelerating plaque development and that antiplatelet therapy might retard disease, a serial study was done to test the latter hypothesis. During period I, ten rhesus monkeys received 58 months of atherogenic feeding. Twice during that period severity of plaque involvement of the abdominal aorta, spermatic, and internal carotid arteries was assessed by angiography, surgical exploration, and biopsy of one femoral artery. Each severity estimate was independently done. Angiography was used to grade luminal intrusion, gross examination and photography to detect abluminal bulging of plaques, and light microscopy to examine wall involvement. At the beginning of period II, three controls were selected to receive continued atherogenic diet for 12 months; seven experimental animals were treated with aspirin, 13.5 mg/kg, and dipyridamole, 15 mg/kg, added to the atherogenic diet. At the end of period II, angiography and femoral arterial biopsy were repeated. All animals were then explored at necropsy, and plaque severity was graded pathologically. Serial platelet survival and serum cholesterol concentrations were obtained periodically throughout this experiment. With feeding, serum cholesterol levels increased to a range of 550–600 mg/dl and, except for one individual, remained in that range during disease induction and antiplatelet interventions. Platelet turnover did not change as atherosclerosis progressed. At the end of the experiment, plasma aspirin concentrations were measured and confirmed medication intake in the experimental animals. During period II, atherosclerosis progressed in all animals except in one treated animal developing diarrhea, weight loss, and resultant hypocholesterolemia of 140 mg/dl. The antiplatelet agents did not arrest disease progression. In fact, treated individuals exhibited more severe atherosclerosis than controls. Medial calcification characterized the arterial wall after treatment. One treated animal sustained a subclavian artery thrombosis as a result of a complicated plaque; this is an unusual event in this animal model. This combination of antiplatelet agents, commonly employed clinically, did not retard and in fact appeared to accelerate subhuman primate dietary atherosclerosis.

Keywords

Rhesus Monkey Antiplatelet Agent Cynomolgus Monkey Inferior Mesenteric Artery Fatty Streak 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Ralph G. DePalma
    • 1
  • Errol M. Bellon
    • 2
  • P. M. Manalo
    • 3
  • Richard A. Bomberger
    • 4
  1. 1.Department of SurgeryGeorge Washington UniversityUSA
  2. 2.Department of RadiologyCase Western Reserve UniversityClevelandUSA
  3. 3.Department of PathologyUniversity of NevadaRenoUSA
  4. 4.Department of SurgeryUniversity of NevadaRenoUSA

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