PERSISTENT INHIBITION OF PLATELETS DURING CONTINUOUS NITROGLYCERIN THERAPY DESPITE HEMODYNAMIC TOLERANCE

Background Nitroglycerin has been shown to possess antiplatelet proper ties in both animals and humans. Tolerance to the hemodynamic effects of nitroglycerin develops with continuous therapy, but it is unclear w hether there is tolerance to its antiplatelet effect. Methods and Resu lts Tolerance to nitroglycerin was studied by exposing porcine aortic media to flowing arterial blood from control pigs (n=9) or pigs treate d with continuous nitroglycerin patches (Nitro-dur, 0.8 mg/h; n=11) at a shear rate of 3397 s(-1) for 3 minutes. Relative to baseline, mean arterial pressure fell by approximate to 10% at 3 and 24 hours (P<.05) but returned to baseline at 48 hours of continuous nitroglycerin trea tment, whereas no significant changes were observed in control animals . Autologous Cr-51-labeled platelet deposition (X10(6)/cm(2)) on the a ortic media at baseline and 3, 24, and 48 hours remained stable in con trol animals, with mean values of 94.8+/-5.9, 89.4+/-8.3, 89.3+/-8.8, and 84.3+/-5.7, respectively. However, in pigs treated continuously wi th nitroglycerin for 48 hours, platelet deposition was reduced signifi cantly at 3 (65.9+/-4.8), 24 (63.8+/-6.4), and 48 hours (56.5+/-7.3) o f nitroglycerin treatment compared with baseline (93.1+/-3.6). Platele t aggregation induced by thrombin also decreased at 3 (12.4+/-1.3), 24 (12.6+/-1.7), and 48 hours (10.8+/-1.6) of nitroglycerin treatment co mpared with baseline (16.3+/-1.4) but remained unchanged in the contro l group. Also, nitroglycerin treatment increased intraplatelet cGMP at 3, 24, and 48 hours compared with baseline. Conclusions This study de monstrates the persistent inhibition of platelet function and platelet deposition on an injured arterial wall by continuous nitroglycerin th erapy despite hemodynamic tolerance.