Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury

Schwartz, Robert S.; Koval, Thomas M.; Edwards, William D.; Camrud, Allan R.; Bailey, Kent R.; Browne, Kevin F.; Vlietstra, Ronald E.; Holmes, David R.

doi:10.1016/0735-1097(92)90303-5

Cited by 156 publications

(37 citation statements)

References 23 publications

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“…Both phenomena, positive remodeling stimulated by intravascular radiation after balloon angioplasty and different patterns of vascular remodeling (positive, negative, or no remodeling) in nonirradiated coronary segments, have been reported previously. 5,18 -20 Although the stimulatory effect of low-dose radiation on plaque proliferation has been demonstrated in injured animal arteries, 6,7 no enhanced plaque growth was observed in the noninjured edges compared with placebo. Plausible explanations for the PV increase in the noninjured edges of both irradiated and placebo groups would be the nonmeasurable vessel injuries caused by the guiding catheter (ie, deep engagement) during the procedure or the devices that cross coronary segments (guidewires, stents, balloons, IVUS catheter, and the 5F radiation delivery catheter).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the potential stimulatory effect of low-dose radiation after injury has been demonstrated in animal studies. 6,7 In consideration that the coronary segments adjacent to the irradiated site will invariably receive a lower dose of radiation to some extent, an important issue remains to be clarified: Does the edge effect also occur in noninjured segments? To address this issue, we (1) assessed the midterm (6 to 8 months) geometrical change of the noninjured edge segments in the irradiated coronary vessels and (2) compared these edge segments with both irradiated segments (IRS) and nonirradiated (sham source), noninjured coronary segments by means of a volumetric 3-D IVUS assessment.…”

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Three-Dimensional Intravascular Ultrasound Assessment of Noninjured Edges of β-Irradiated Coronary Segments

et al. 2000

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Background-The "edge effect," late lumen loss at the margins of the treated segment, has become an important issue in the field of coronary brachytherapy. The aim of the present study was to assess the edge effect in noninjured margins adjacent to the irradiated segments after catheter-based intracoronary ␤-irradiation. Methods and Results-Fifty-three vessels were assessed by means of 3-dimensional intravascular ultrasound after the procedure and at 6-to 8-month follow-up. Fourteen vessels (placebo group) did not receive radiation (sham source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5 mm in length) were identified as noninjured, whereas 18 noninjured edges were selected in the placebo group. We compared the volumetric intravascular ultrasound measurements of the noninjured edges of the irradiated vessels with the fully irradiated nonstented segments (IRS, nϭ27) (26-mm segments received the prescribed 100% isodose) and the noninjured edges of the vessels of the placebo patients. The lumen decreased (6 mm 3 ) in the noninjured edges of the irradiated vessels at follow-up (Pϭ0.001). We observed a similar increase in plaque volume in all segments: noninjured edges of the irradiated group (19.6%), noninjured edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume increased in the IRS in the 3 groups. No edge segment was subject to repeat revascularization. Conclusions-The edge effect occurs in the noninjured margins of radiation source train in both irradiated and placebo patients. Thus, low-dose radiation may not play an important role in this phenomenon, whereas nonmeasurable device injury may be considered a plausible alternative explanation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Three-Dimensional Intravascular Ultrasound Assessment of Noninjured Edges of β-Irradiated Coronary Segments

et al. 2000

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“…In these prior studies, the intercept of the injury-neointimal thickness regression line was responsive to therapies, whereas the slope changed minimally. 12 The differential arterial response to injury, measured by the slope of the injury-neointimal thickness regression line, appears relatively constant within the pig species. It is possible that each species may have a characteristic injury-neointimal thickness slope, determined by the linear regression methods of this study.…”

Section: Discussionmentioning

confidence: 99%

Differential neointimal response to coronary artery injury in pigs and dogs. Implications for restenosis models.

Schwartz

Edwards

Bailey

et al. 1994

Arterioscler Thromb

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Neointimal hyperplasia occurs in the coronary arteries after percutaneous revascularization procedures and is a reparative response that frequently causes recurrent stenosis. Prior animal studies have shown that neointimal tissue thickness is proportional to the depth of arterial injury. Because animal models are increasingly used to test therapeutic strategies against restenosis, the purpose of this study was to evaluate the degree of neointimal thickening formed in the coronary arteries of pigs compared with dogs in response to severe injury. Fourteen coronary arteries in six mongrel dogs and 18 coronary arteries in nine pigs underwent severe arterial injury using tantalum metal coils delivered on oversized angioplasty balloons. Animals were killed after 4 weeks, and all coronary arteries were pressure perfusion fixed. Mean histological injury scores and neointimal thicknesses for dogs were 1.9±0.3 and 0.30±0.11, respectively, compared with 2.1±0.7 and 0.71 ±0.36 for pigs. Thus, there was significantly less C oronary artery restenosis remains a major unsolved limitation for interventional cardiology. 13 It results from arterial injury incurred during the revascularization of coronary atherosclerosis 46 and is caused in large part by neointimal hyperplasia at the injury site. 79 Little progress has been made against restenosis despite much investigative work in both patients and animal models.The relevance of animal models to restenosis in humans is unclear yet of paramount importance to clinical trials. Neointima develops in most animal models but to varying degrees and with variable histopathologic appearance. In the porcine coronary model, large amounts of neointima develop with histopathology identical to that in humans. 10 The depth and extent of arterial injury appear to determine the thickness of neointimal response.11 In other models, less neointima may form in response to injury. If this suspicion is true, comparative study of animal models resulting in less neointima might be useful for understanding the mechanisms of neointimal growth and possibly for suggesting new therapeutic approaches to restenosis. Thus, the purpose of this study was to Received March 30, 1993; revision accepted December 7, 1993. neointimal thickening in dogs compared with pigs (P<.001) despite no differences in injury (P=NS). The neointimal thickening differences translated into significantly different percent area stenoses: 55 ±24% for pigs versus 27 ±13% for dogs (P<.001). Linear regression modeled neointimal thickness versus injury assessed by an ordinal injury score proportional to the depth of injury for each species. This analysis confirmed the differences across multiple injury levels. The slope of the regression line for dogs was small, suggesting that no relation may exist between injury and neointimal thickness in this species. The pig may be a more appropriate model for the study of the genesis of stenosing neointima. If the lack of response in dogs could be better understood, insight into more effective r...

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“…The first study of external radiation in coronary vessels was carried out by Schwartz at the Mayo Clinic who tested doses of 4 and 8 Gy delivered by an orthovoltage unit to stented pig coronary arteries. 21 Morphometric analysis carried out four weeks later revealed poorer results in the irradiated animals compared to the controls with the highest dose group faring the worst. This study has been criticized on the basis of magnitude of vessel injury, the use of orthovoltage x-rays and the relatively low doses of radiation which were tested.…”

Section: Preclinical Studies Of Coronary Radiotherapy a Externalmentioning

confidence: 93%

Radiation therapy to prevent coronary artery restenosis

Crocker

1999

Seminars in Radiation Oncology

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Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury

Cited by 156 publications

References 23 publications

Three-Dimensional Intravascular Ultrasound Assessment of Noninjured Edges of β-Irradiated Coronary Segments

Three-Dimensional Intravascular Ultrasound Assessment of Noninjured Edges of β-Irradiated Coronary Segments

Differential neointimal response to coronary artery injury in pigs and dogs. Implications for restenosis models.

Radiation therapy to prevent coronary artery restenosis

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