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Minimal Duration of Oral Matrix Metalloproteinase Inhibition to Prevent Constrictive Arterial Remodeling after Balloon Dilation in the Pig¹

¹ From the Experimental Cardiology Laboratory, University Medical Center, Heidelberglaan 100, Room G02.523, Utrecht, the Netherlands. Received March 6, 2001; revision requested April 9; revision received June 1; accepted July 5. Supported by grant NHS 99.209 from the Dutch Heart Foundation. M.J.S. supported by the Sorbo Foundation. Address correspondence to G.P. (e-mail: g.pasterkamp@hli.azu.nl).

PURPOSE: To determine the minimal duration of oral matrix metalloproteinase (MMP) inhibition to prevent constrictive remodeling after balloon dilation.

MATERIALS AND METHODS: In 37 nonatherosclerotic pigs, balloon dilation was performed in 145 peripheral arteries. Pigs were treated with an MMP inhibitor for 2, 7, 14, 28, or 42 days, or they served as controls and were killed 42 days after intervention. Arteries were visualized with angiography and intravascular ultrasonography.

RESULTS: A 69% reduction in late vessel area (VA) loss was achieved after 14 days of treatment: 1.27 mm² ± 0.55 (standard error of the mean [SEM]) versus 4.04 mm² ± 0.93 (SEM) in the control group (P = .1). A consistent inhibition of late VA loss was observed in the 28-day (0.89 mm² ± 0.83 [SEM], P = .03) and 42-day (0.74 mm² ± 0.66 [SEM], P = .02) groups treated with the MMP inhibitor. After 14 and 28 days of treatment, late lumen area loss was 65% and 55% of control values, and it decreased to 41% (P = .04) after 42 days of treatment.

CONCLUSION: MMP inhibition for 14–28 days is sufficient to inhibit constrictive remodeling after balloon dilation. This implies that an essential MMP-dependent initiator of constrictive remodeling was mainly active in the first 2 weeks after intervention.

Index terms: Animals • Arteries, peripheral, 92.454, 98.454 • Arteries, transluminal angioplasty, 92.454, 98.454 • Arteries, US, 92.1298, 98.1298 • Experimental study • Ultrasound (US), intravascular, 92.1298, 98.1298

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