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Published on: July 16, 2018
Microembolization Effects of Imipenem/Cilastatin In Vivo Depicted by Monochromatic Synchrotron X-Ray Microangiography
Hiroki Nakamura1, Akira Yamamoto1, Hiroyuki Watanabe1
1Department of Radiology, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
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.
Insights
Imipenem (IPM)/cilastatin (CS) selectively occluded inflamed microvessels in rabbits, with normal vessels reopening within 70 minutes. This study highlights IPM/CS as a potential embolic agent for targeting neovascularization in inflammation.
Area of Science:
- Vascular Biology
- Interventional Radiology
- Pharmacology
Background:
- Neovascularization is a hallmark of inflammatory processes.
- Effective embolization of neovasculature requires agents with selective targeting capabilities.
- Imipenem (IPM)/cilastatin (CS) is an antibiotic combination with potential as an embolic material.
Purpose of the Study:
- To investigate the embolic characteristics of imipenem (IPM)/cilastatin (CS) in microvessels in vivo.
- To evaluate the selective embolic effect of IPM/CS on normal versus inflammation-induced neovasculature.
Main Methods:
- A rabbit auricular inflammation model was established using picibanil (OK-432).
- Microangiography with monochromatic X-rays from synchrotron radiation was employed.
- Embolization was performed using a mixture of IPM/CS and contrast medium in normal and inflamed auricular arteries.
Main Results:
- Immediately post-embolization, mean vessel diameter at normal sites was 267 μm.
- Normal vessels recanalized within a mean of 70 minutes (50-70 minutes).
- Inflamed vessels showed no recanalization up to 90 minutes post-embolization.
Conclusions:
- Imipenem (IPM)/cilastatin (CS) initially occludes vessels larger than its particles.
- The embolic effect resolved in normal vessels within 70 minutes.
- IPM/CS demonstrated a selective and persistent embolic effect on inflammation-related neovasculature.

