The association of in vitro arachidonic acid responsiveness and plasma thromboxane levels with early platelet deposition on the luminal surface of small-diameter grafts

Michael Freeman, Gregorio A. Sicard, Leonardo I. Valentin, Sonia Neuberger, Martin J. Mangino, Charles B. Anderson

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Abstract

The response of canine platelets to arachidonic acid (AA) stimulation was studied as a predictor of thrombotic potential. Fifty mongrel dogs underwent in vitro platelet aggregation studies with adenosine diphosphate (ADP), collagen, and AA used as inducing agents. Thirty-two dogs were selected on the basis of their response to AA stimulation. Platelet aggregation in response to AA stimulation occurred in 16 (responders) and 16 showed no aggregatory response (nonresponders). The animals were divided into four groups. Group I received no antiplatelet agents (control); group II received U-63,557A, a specific thromboxane synthetase inhibitor (TSI); group III received aspirin; and group IV received aspirin and TSI. Polytetrafluoroethylene grafts were implanted in the carotid and femoral arteries of the dogs in all four groups. Plasma thromboxane (TxB2) levels were drawn before drug treatment and 4 weeks after surgery. Platelet deposition on the luminal surface of the implanted grafts was studied in vivo with a technique that uses both 111In-labeled platelets and 99mTc-labeled red blood cells and was expressed as percentage of indium excess (%IE). Group I (control) dogs whose platelets aggregated in response to AA stimulation had significantly higher 24-hour platelet deposition (%IE) on the luminal surface of implanted grafts (p < 0.02), lower 4-week graft patency (p < 0.002), and higher plasma TxB2 levels (p < 0.01) than those dogs whose platelets did not aggregate. In contrast to the results of AA stimulation, neither ADP nor collagen responsiveness was discriminatory for the thrombotic potential of canine arteries as measured by 24-hour platelet deposition (%IE), 4-week graft patency, or plasma TxB2 levels. Pharmacologic platelet inhibition by use of aspirin (groups III and IV) effectively transformed AA responders into AA nonresponders as manifested by lowering the 24-hour platelet deposition (%IE) and increasing the 4-week patency to a value similar to AA nonresponders. This study confirms that the in vitro platelet response to AA stimulation is the best method for determining the endogenous thrombotic potential of canine arteries and correlates well with plasma TxB2 levels and 24-hour in vivo platelet deposition studies.

Original languageEnglish (US)
Pages (from-to)554-561
Number of pages8
JournalJournal of Vascular Surgery
Volume7
Issue number4
DOIs
StatePublished - Jan 1 1988

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Thromboxanes
Arachidonic Acid
Blood Platelets
Transplants
Dogs
Thromboxane-A Synthase
Aspirin
Canidae
Platelet Aggregation
Adenosine Diphosphate
In Vitro Techniques
Collagen
Arteries
Indium
Platelet Aggregation Inhibitors
Polytetrafluoroethylene
Femoral Artery
Carotid Arteries
Erythrocytes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

The association of in vitro arachidonic acid responsiveness and plasma thromboxane levels with early platelet deposition on the luminal surface of small-diameter grafts. / Freeman, Michael; Sicard, Gregorio A.; Valentin, Leonardo I.; Neuberger, Sonia; Mangino, Martin J.; Anderson, Charles B.

In: Journal of Vascular Surgery, Vol. 7, No. 4, 01.01.1988, p. 554-561.

Research output: Contribution to journalArticle

Freeman, Michael ; Sicard, Gregorio A. ; Valentin, Leonardo I. ; Neuberger, Sonia ; Mangino, Martin J. ; Anderson, Charles B. / The association of in vitro arachidonic acid responsiveness and plasma thromboxane levels with early platelet deposition on the luminal surface of small-diameter grafts. In: Journal of Vascular Surgery. 1988 ; Vol. 7, No. 4. pp. 554-561.
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