Biocompatibility of tetramethylpyrazine-eluting stents in normal porcine coronary arteries

Abstract

Objective: Drug-eluting stents have been used to markedly decrease in-stent restenosis in 6 months, but they are noticed due to the late thrombogenicity. The purpose of the present study was to evaluate the biocompatibility of Tetramethylpyrazine-eluting stents by investigating the intimal response and thrombogenicity in normal porcine coronary arteries by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS) and histomorphometry.

Methods: Bare metal stents (BMS) were uniformly spray-coated with Tetramethylpyrazine (TMP 200 microg) and prepared for TMP-eluting stents (TES). Fourteen coronary arteries in 14 pigs underwent stent implantation. Seven TES were implanted in 7 pigs and 7 BMS in other 7 pigs. The stents were deployed with a stent-to-artery ratio of 1.1-1.2/1.0 in order to induce vascular wall injury. QCA and IVUS were performed before and immediately after the implantations and at 28 days (end time point). The analysis on blood cell count, biochemical parameters, status of behavior of pigs were evaluated before the implantation and at the time of 1 and 28 days. Stented-coronary arteries, stented-coronary arteries related ventricular wall, lung, liver and kidney were harvested after euthanasia of animals at the endpoint. Histopathology and histomorphometry had been done to assess the local toxicity of TES to these organs.

Results: All the stents were successfully implanted, however, 4 pigs died of cardiac tamponade or anesthesia. No bone marrow depression and hemolysis was seen. No damage to the function and metabolism of liver and kidney was discovered. No thrombosis was found in control and test groups. Few inflammatory cells were found in the stented-coronary artery walls at each endpoint in both groups. No damage to stented-coronary arteries related ventricular wall, lung, liver and kidney was detected due to TES implantation. Compared with the control group, the neointimal area was significantly reduced in the TES group (60.2+/-23.5% vs 10.0+/-2.1%, P=0.01) by IVUS analysis, but the lumen area in the TES group was increased (4.34+/-0. 93 mm(2) vs 1.29+/-1.02 mm(2), P=0.011), the neointimal area was reduced markedly (1.51+/-0.45 mm(2) vs 4.60+/-1.39 mm(2), P=0.004).

Conclusions: The biocompatibility of TES in porcine model at 28 days seems to be good and acceptable. Biocompatibility can be evaluated by IVUS and histopathology in a porcine restenosis model.