| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2003;76:1528-1532
© 2003 The Society of Thoracic Surgeons
a Cardiovascular Surgery Discipline, Escola Paulista de Medicina and São Paulo Hospital, Federal University of São Paulo, São Paulo, Brazil
Accepted for publication May 6, 2003.
* Address reprint requests to Dr Gomes, Cardiovascular Surgery Discipline, Escola Paulista de Medicina, Federal University of São Paulo, Rua Botucatu 740, São Paulo, SP 04023-900, Brazil
e-mail: wjgomes.dcir{at}epm.br
Abstract
BACKGROUND: Intracoronary stents have been extensively used in percutaneous coronary revascularization. However, despite the breakthroughs and developments associated with this new technology, novel complications and findings have emerged compelling the cardiac surgeon to cope with this new scenario. The presence of an intracoronary foreign body (stent) might induce an inflammatory reaction to the coronary artery and surrounding cardiac muscle.
METHODS: Six patients who previously (2 to 72 weeks) underwent stent insertion and subsequently coronary artery bypass graft surgery had a biopsy taken from the grafted coronary artery distal to the stent and from the adjacent muscle. The samples were processed and stained with hematoxylin and eosin and histologically studied.
RESULTS: Histologic examination of the coronary artery distal to the stent revealed chronic inflammation and an intimal acute inflammatory infiltrate, with polymorphonuclear leukocytes. The myocardium adjacent to the stent exhibited a significant chronic inflammatory infiltrate and fibrosis, compatible with myocarditis.
CONCLUSIONS: The presence of an intracoronary stent induces a persistent, acute and chronic inflammatory reaction, with involvement of the distal coronary artery and surrounding myocardium. This may have implications when choosing the optimal site distal to the stent for coronary artery bypass grafting.
Coronary stents have rapidly expanded and become accepted worldwide for treatment of coronary artery disease. Since their introduction in 1987, intracoronary stents are used almost routinely in percutaneous coronary revascularization [1]. This has resulted in novel complications and findings when surgery is subsequently required. Although the early results are regarded as satisfactory, the effects and aftermath of introducing an intracoronary foreign body (metallic stent) have been poorly studied. The presence of these intracoronary foreign bodies might induce an inflammatory reaction and have possible functional and structural repercussions for the coronary artery and surrounding cardiac muscle.
This work was conceived to study the nature and involvement of the inflammatory process on the coronary artery wall downstream of the stent site and on the surrounding myocardium. The histologic appearance of the coronary artery distal to the stent and surrounding muscle were studied in patients undergoing coronary surgery.
Patients and methods
Patients
Six patients (age range, 48 to 74 years; 4 men and 2 women) who previously underwent stent implant and subsequently had coronary artery bypass graft surgery were studied. The operative indication was progression of native coronary artery disease or in-stent restenosis. The time elapsed from the stent insertion to the coronary artery bypass graft surgery varied from 2 to 72 weeks. The stented coronary arteries were the left anterior descending artery (5 patients) and the right coronary artery (1 patient). The operations were electively scheduled, but 1 patient who exhibited coronary thrombosis 2 weeks after stenting had an urgent operation. The study protocol was approved by the Ethics Committee of the Federal University of São Paulo.
Sample technique and processing
At the time of the operation, routine coronary arteriotomy for anastomosis was performed 10 to 20 mm downstream of the stented site. The arteriotomy length was about 5 to 7 mm long. A 1-mm-wide spindle-shaped fragment was removed from the edge (Fig 1).
These tiny fragments were carefully handled to avoid distortion or damage and immediately fixed in 10% buffered formalin; they were later embedded in paraffin, and 5-µm sections were cut. Sections from both coronary and myocardial fragments were stained with hematoxylin and eosin. Light microscopic examination of the fragment sections was performed by an experienced pathologist, who visually selected the most representative images. In 4 patients a myocardial biopsy was taken adjacent to the stent site, using a Tru-cut biopsy needle (Baxter Healthcare, Deerfield, IL).
|
The analysis of the coronary artery fragments revealed an intimal and medial inflammatory process, varying from mild to intense. A persistent, acute intimal inflammatory infiltrate with polymorphonuclear leukocytes was present even 18 months after stenting. Figure 2 shows a mild inflammatory process in a sample collected 4 weeks after stenting, with leukocyte infiltration in the tunica intima and media. Figure 3 depicts a moderate-to-intense inflammatory reaction found in a specimen harvested 18 months after stenting. Neutrophils are seen infiltrating the endothelium, disclosing an acute reaction. Edema of the elastic layer and arterial wall thickening are also noted.
|
|
|
|
|
The impetus to undertake this work came from our observation that when operating on patients with stented coronary arteries, we noticed that the coronary artery and tissues surrounding it seemed more inflamed, friable, and easily caused to ooze. It is well known that metal parts inserted into the body produce a type of response known as foreign body granuloma. The primary cells are macrophages containing large numbers of phagocytic vacuoles with few secretory organelles [2]. Granulomas are not static formations; in fact the rate of cell turnover is high. Several cytokines have been identified as mediators involved in the formation and maintenance of these granulomas: interleukin 2, interferon-
, tumor necrosis factor-
, and interleukin 1 [3]. This response can be synergistic with the atherosclerotic plaque, in which activated macrophages account for roughly 25% of the population of inflammatory cells [4]. Moreover, macrophage content in the culprit lesion may be a marker for restenosis after coronary interventions [5].
Coronary stenting appears to cause a more severe arterial injury [6, 7] and a more intense inflammatory response within the vessel wall than other modalities of percutaneous interventions [8, 9].
The arterial overdistension and vascular injury caused by the balloon and stent placement acts as a potent stimulus for proliferation of smooth muscle cells and neointimal hyperplasia [10, 11]. To date animal and clinical studies have suggested that the arterial injury provoked by balloon insufflation might be responsible for the cellular response [12, 13]. However, the vascular injury caused by placement of a coronary stent is more aggressive. The stent struts cause focal deep vascular trauma, and the rate and duration of cellular proliferation exceeds those of balloon injury. These effects may be further potentiated by the prolonged mechanical strain applied by the stent on the coronary artery wall. The effect of residual foreign material after stenting includes chronic inflammation [14]. Recently there is growing evidence that stenting is associated with increased inflammatory cell infiltration within the arterial wall [8, 9, 15, 16].
Farb and colleagues [16] have demonstrated that early after stenting (<11 days), fibrin, platelets, and acute inflammatory cells were nearly always present in association with stent struts. Chronic inflammation was also commonly observed adjacent to the struts, particularly longer than 12 days after stenting.
A recent study investigating long-term release of proinflammatory cytokines after stent implant endorses our finding. In this report the level of serum soluble interleukin 2 receptor for T-lymphocyte activation (as a marker of cell-mediated immunity) was still elevated 4 months after stenting. Proinflammatory cytokines and acute-phase proteins were also released into the peripheral circulation early after coronary stenting, and cell-mediated immunity persisted at least 12 weeks after stenting [17].
Besides the direct inflammatory effect, embolization may play a pivotal role on the inflammatory process. Distal coronary embolization visible on angiography during angioplasty has been reported in 15% of patients and related to poor prognosis [18]. It has been confirmed in a subgroup study of the SYMPHONY and second SYMPHONY trials, which was designed to assess the incidence and clinical significance of elevated cardiac troponin I after percutaneous coronary revascularization. Overall, 48% of patients had elevated cardiac troponin I after percutaneous coronary revascularization, and it was associated with significantly higher risk of death or infarction and worse 90-day clinical outcomes [19]. The incidence of troponin I release has been higher in the patients undergoing stent implantation than in patients treated with angioplasty alone [19–21].
A striking implication of stent inflammatory reaction is related to endothelial function. Caramori and associates [22] studied patients treated at least 6 months earlier with coronary intervention for isolated proximal left anterior descending stenosis, with no evidence of restenosis. They have shown that severe coronary endothelial dysfunction was observed long-term after stenting as compared with balloon angioplasty or atherectomy. This suggests that stents can cause significant acceleration of coronary artery disease distally. Also, stenting can have systemic repercussions. Wu and coworkers [23] investigated systemic endothelial function on forearm resistance vessels after coronary stenting. In patients with angiographic restenosis after coronary stenting, the forearm reactive hyperemia was more impaired and may be related to endothelin-1 that is generated by the endothelium and increased in the coronary circulation immediately after percutaneous coronary revascularization [24]. Endothelin-1 acts as both a potent vasoconstrictor and a stimulator of the proliferation of vascular smooth muscle cells [25].
Our finding in the case of stent thrombosis, in which the adjacent vessels were occluded by massive thrombosis, suggests an interesting possibility, that urgent surgical revascularization in this setting may be worthless because the microvascular circulation is compromised by massive thrombosis preventing reperfusion. Our finding may also have implications with respect to the accelerated progression of arteriosclerosis in coronary arteries subjected to percutaneous coronary revascularization and stent implantation.
Although this study has addressed complicated stent cases, the majority being restenosis, it may represent a sizable part of the stented coronary arteries, as the restenosis rate in bare stent has been more than 36% (SIRIUS trial) and even more in nonselected patients.
To date, no other reports exist on the myocardial compromise as a result of the surrounding stent inflammatory reaction, as we found here. Additional studies are required to fully characterize the extension and consequences to the coronary arteries and myocardium of the inflammatory reaction after stenting.
In conclusion, the presence of an intracoronary stent induces an acute and chronic inflammatory reaction, even at the late period, with involvement of the distal coronary artery and surrounding myocardium. Further studies are necessary to assess the inflammatory process extension and its consequences. Also the operative technique used may need modification in such instances.
Acknowledgments
We are indebted to Professor G. D. Angelini, from the Bristol Heart Institute, Bristol, UK, for kindly reviewing the manuscript.
References
This article has been cited by other articles:
|
|
 |
|
  C. Rao, R. D. L. Stanbridge, J. Chikwe, J. Pepper, P. Skapinakis, O. Aziz, A. Darzi, and T. Athanasiou Does Previous Percutaneous Coronary Stenting Compromise the Long-Term Efficacy of Subsequent Coronary Artery Bypass Surgery? A Microsimulation Study Ann. Thorac. Surg., February 1, 2008; 85(2): 501 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E K Iliodromitis, S Kyrzopoulos, I A Paraskevaidis, K G Kolocassides, S Adamopoulos, G Karavolias, and D T Kremastinos Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning? Heart, December 1, 2006; 92(12): 1821 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Gomes and E. Buffolo Coronary stenting and inflammation: implications for further surgical and medical treatment. Ann. Thorac. Surg., May 1, 2006; 81(5): 1918 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Gomes, O. Giannotti-Filho, N. A. Hossne Jr, R. Catani, and E. Buffolo Inflammatory Reaction After Sirolimus-Eluting Stent Implant Ann. Thorac. Surg., November 1, 2005; 80(5): 1903 - 1904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Orlandi, A. Francesconi, M. Marcellini, A. Ferlosio, and L. G. Spagnoli Role of ageing and coronary atherosclerosis in the development of cardiac fibrosis in the rabbit Cardiovasc Res, December 1, 2004; 64(3): 544 - 552. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
