Embolic Characteristics of Imipenem-Cilastatin Particles in Vitro and in Vivo: Implications for Transarterial Embolization in Joint Arthropathies

Purpose: To elucidate in vitro and in vivo characteristics and embolic properties of imipenem-cilastatin (IPM-CS) compared with hydrogel microspheres. Materials and Methods: Particle size distribution was microscopically evaluated with 3 samples of 50 mg IPM-CS suspensions in each of 6 conditions by a mixture of contrast volume: 500 or 1000 mu L and vortex mixing time: 5, 10, or 30 s. Time-dependent changes up to 3 h post-mixing were also evaluated. Fifteen male Sprague-Dawley rats (460.2 +/- 5.0 g) underwent unilateral renal artery embolization using IPM-CS (n = 11) or hydrogel microspheres (n = 4). Follow-up angiography 48 h after embolization and histological evaluation, including acute tubular necrosis (ATN) and inflammation, were scored using a 5-point scale (from 0 = normal to 4 = severe). Results: Over 91% of IPM-CS particles were <40 mu m under all in vitro conditions. With the increased contrast volume, the average particle size also increased (mean +/- standard deviation: 11.6 +/- 13.9 vs 16.7 +/- 18.2 mu m for 500 and 1000 mu L iodinated contrast, P <.001); however, the impact of the mixing/elapsed time were limited. At 48 h after embolization, all cases in the IPM-CS groups (11/11) showed major to complete recanalization versus no recanalization with hydrogel microspheres (0/4) (P <.001). The following are the median ATN and inflammation grades in the cortex (ventral/dorsal) and medulla (ventral/dorsal) in both groups: IPM-CS, ATN in cortex (2/4) and medulla (1/1), inflammation in cortex (0/0) and medulla (0/0); hydrogel microspheres, ATN in cortex (4/4) and medulla (3/2), inflammation in cortex (1/1) and medulla (1/1). Conclusions: IPM-CS suspension generated particles that were predominantly smaller than 40 mu m and with unique short-term embolic effects, leaving predominantly peripheral ischemic changes.