A reexamination of the angiotoxicity of superselective injection of DMSO in the swine rete embolization model

Abstract

Background and purpose: There are a variety of embolization applications for non-adhesive, liquid agents. We reevaluated the potential microvascular angiotoxicity of superselective infusions of dimethyl sulfoxide (DMSO) using very long infusion rates in a previously described animal model.

Methods: Twenty-six swine underwent percutaneous femoral puncture for superselective catheterization of the artery of the rete while being continuously monitored for ECG and intraarterial pressure. Two volumes (0.5 or 0.8 mL) and three durations (30, 60, and 90 seconds) of superselective infusion of DMSO were used to evaluate the effect of a single-dose rate within an ipsilateral rete. Contralateral control infusions of normal saline were also administered. Acute hemodynamic and angiographic outcomes were assessed. After recovery, follow-up angiography and sacrifice were performed at either 10 or 28 days. Brains and retia were harvested for gross and microscopic histopathologic evaluation.

Results: No significant hemodynamic alterations occurred acutely. Twenty-three of the 24 infused retia showed variable acute vasospasm that typically was mild to moderate in severity and transient (10 to 20 minutes). Follow-up angiography at sacrifice always showed normal retial arterial anatomy. No adverse clinical sequelae were noted. Gross inspection of brains showed no evidence of infarction or subarachnoid hemorrhage. Microscopic histopathologic examination of retia showed mostly nonspecific changes in both exposed and control samples. Possible causal histotoxicity was seen in four retia (three of four exposed to higher dose rates), in which involvement was limited to one to three retial arteries.

Conclusion: Lower total dose and dose rates of superselective infusion of DMSO into the retial microarterial network resulted in substantially less angiotoxicity than that found in a previous study, as defined by clinical, angiographic, gross, and histopathologic criteria.

fig 1.

Angiographic demonstration of vasospasm associated with DMSO infusion. A, DSA from superselective left ascending pharyngeal artery injection (anteroposterior projection) shows normal filling of the ascending pharyngeal and retial system. B, Repeat DSA from selective left CCA injection 3 minutes after infusion of 0.8 mL DMSO over 90 seconds shows grade 3 vasospasm affecting the ascending pharyngeal artery (arrow). C, Repeat DSA from left CCA injection 12 minutes after DMSO infusion shows complete resolution of vasospasm.

fig 2.

Nonspecific microscopic histopathologic changes in both control and exposed retia. A, Control rete: extensive separation and sloughing of otherwise normal-appearing endothelial cells (short arrows) are seen within multiple microarteries, most likely the result of preparation artifacts. There is also mild periadventitial inflammation (long arrows) (hematoxylin-eosin, original magnification ×100). B, Control rete: endoluminal refractile bodies (short arrows) are seen in association with granulomatous inflammation and foreign body giant cells (long arrow) (hematoxylin-eosin, original magnification ×150).

fig 3.

Microscopic histopathologic changes in exposed retia possibly attributable to DMSO angiotoxicity. A, Exposed rete (0.8 mL per 30 seconds): single microartery shows extensive transmural chronic inflammation and angionecrosis (hematoxylin-eosin, original magnification ×150). B, Exposed rete (0.8 mL per 60 seconds): single microartery is completely occluded with amorphous foreign material and has focal transmural chronic inflammation (arrows) (hematoxylin-eosin, original magnification ×150). C, Exposed rete (0.8 mL per 90 seconds): single microartery shows only moderate intimal hyperplasia (hematoxylin-eosin, original magnification ×150). D, Exposed rete (0.8 mL per 60 seconds): single microartery shows evidence of focal angionecrosis and endoluminal granulomatous inflammation with foreign body giant cell formation (arrow) (hematoxylin-eosin, original magnification ×150).