Prolongation of experimental cardiac allograft survival with thromboxane-related drugs

A novel receptor antagonist, 3-hydroxymethyl-dibenzo (b,f) thiepin 5,5-dioxide (L-640,035) and the thromboxane synthase inhibitor, sodium (E) -3-(4-[3-pyridylmethyl phenyl]) -2-methyl-acrylate (OKY 1581) were evaluated for their effect in promoting the survival of cardiac allografts in Lewis rats that received cardiac allografts from Lewis x Brown-Norway F1 rats. Neither of these drugs or azathioprine alone significantly prolonged graft survival. However a combination of azathioprine with either of the two drugs significantly increased graft survival. Because L-640,035 inhibits platelet and smooth muscle responses to thromboxane-mimics, and because OKY 1581 is a specific thromboxane synthase inhibitor, we conclude that thromboxane may have a causal role in experimental cardiac allograft rejection in rats.