Microembolization Effects of Imipenem/Cilastatin In Vivo Depicted by Monochromatic Synchrotron X-Ray Microangiography

Purpose

To elucidate the characteristics of imipenem (IPM)/cilastatin (CS) as an embolic material in microvessels in vivo.

Materials and Methods

Three healthy rabbits were injected subcutaneously in 1 auricle with picibanil (OK-432) in advance to create an inflammation-induced neovascular model. Microangiography was performed using monochromatic X-rays obtained from a large synchrotron radiation facility (SuperPhoton ring-8 GeV, SPring-8). All rabbits underwent pre-embolic microangiography under anesthesia. Embolization from the central branch of the auricular artery was then performed using a mixture of IPM/CS (0.2 g) + nonionic contrast medium (2 mL). Microangiography was performed immediately after and at 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after embolization. The diameter of embolized vessels was measured from the images immediately after embolization. Recanalization times were evaluated from immediately after embolization to 90 minutes after embolization, and they were compared between normal sites and sites where inflammation was induced.

Results

The mean diameter of the embolized vessels immediately after embolization evaluated at the normal site was 267 μm (SD ± 58.35; range, 174–363 μm). Evaluation of postembolic recanalization showed that vessels in the normal sites recanalized after a mean of 70 minutes (range, 50–70 minutes), whereas vessels at the sites of inflammation did not recanalize in observations up to 90 minutes after embolization.

Conclusions

Microangiography using monochromatic X-rays produced from large synchrotron radiation showed that vessels larger than the IPM/CS particles were initially occluded, but the embolic effect resolved in normal vessels within 70 minutes and persisted in inflamed vessels. IPM/CS may thus exert a selective embolic effect on inflammation-related neovasculature.