Acute vasculitis after endovascular brachytherapy

Abstract

Coronary artery angioplasty, with or without stent deployment, relieves myocardial ischemia but is followed by a high rate of re-stenosis. Endovascular radiation (beta or gamma) at the time of angioplasty prevents re-stenosis in a large proportion of vessels in swine (short term) and humans (short and long term). We have found an unexpected lesion in swine exposed to endovascular beta brachytherapy from 32P sources: an acute necrotizing vasculitis in arterioles located in the peri-adventitial tissues of the irradiated coronary arteries, beyond the vasa-vasorum. It is characterized by fibrinoid necrosis of the arteriolar media, often extending into its intima and adventitia, and occasionally associated with leukocytic exudate or thrombosis. The affected vessels measure 50 to 250 μm in diameter (average 132 μm) and are located 0.38 to 2.05 mm from the intima of the corresponding coronary artery (as determined in section planes perpendicular to the artery). This lesion has only occurred in samples subjected to radiation. There is no association with the effects produced in the main vessel by angioplasty or stenting, including rupture of elastic lamellae, degree of medial loss, fibrinous exudate, hemorrhage, thrombosis or fibrosis. Although occasionally more than one small vessel is affected at a given section plane, there are usually several uninvolved vessels within the same range of distance from the main artery. The prescribed dose to the coronary arteries has been 3500 cGy at a depth of 0.5 mm from the surface of the intima (approximately 2000 cGy at 1 mm). The dose rate has varied from 25 to 275 cGy/second. A special device has centered the radiation source in the lumen of the main vessel. The dose received by the affected arterioles at the site of vasculitis (as calculated in paraffin sections of tissues subjected to formalin fixation at 150 mm/Hg) has varied approximately between 4000 cGy (for those closest to the main vessel) and 600 cGy (for those farthest). In 3 separate experiments the incidence of this acute vasculitis at one month post-radiation has been 51 % (28/55 porcine coronary vessels exposed to 32P). By six months the incidence of acute vasculitis has decreased to 14 % (4/28 irradiated vessels); however at this late stage there is neointimal proliferation and sclerosis in 46 % of these small vessels, often with significant lumenal narrowing. This suggests that the healing phase of the acute vasculitis occurs within a period of months and can result in considerable deficit of local blood flow. Small vessel vasculitis is not limited to the tissues surrounding the coronary arteries; in a separate experiment acute vasculitis has been detected also around porcine iliac arteries exposed to 32P (6/6 irradiated vessels). These observations indicate that endo-arterial brachytherapy using 32P results in vascular effects beyond the adventitia of the target vessel. This necrotizing vasculitis appears to be causally related to radiation, but its mechanism is unclear. It is likely that the same lesion also occurs in humans. To our knowledge it has not been reported until now, either in the experimental models or in the few human specimens examined after angioplasty/brachytherapy.