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A study of the sequential morphologic changes after manual coronary endarterectomy
J THORAC CARDIOVASC SURG 1991;102:890-4
A study of the sequential morphologic changes after manual coronary endarterectomy Manual coronary endarterectomies heal in the long-term by a poorly understood process of myofibrointimal proliferation. A retrospective analysis of detailed cardiovascular pathologic examinations of 51 patients dying at varying intervals after endarterectomy provides insight into the sequence of this proliferative response. Twenty-one patients died within 7 days, 6 at 8 to 30 days, 3 at 31 days to 6 months, 4 at 6 months to 5 years, and 17 at more than 5 years after endarterectomy. The observations made suggest that the denuded arterial surface heals after the fibrin-platelet mural thrombus that covers it is organized and is replaced by fibrosis and myofibroblast proliferation. In unusual cases proliferation is exuberant, resulting in significant restenosis, an outcome in which recurrent atherosclerosis contributes to only a minor degree. This is the first series in which the sequential reparative changes at varying times after manual coronary endarterectomy have been studied.
V. M. Walley, MD,a R. W. Byard, MBBS,b and W. J. Keon, MD,a Ottawa, Ontario. Canada. and North Adelaide, Australia
Coronary endarterectomy performed at the time of bypass grafting enables otherwise diffusely diseased and inoperable arteries to be grafted. 1 The procedure is most often done manually.l? Although the reaction to carotid endarterectomy has been previously well documented.vP the response to this procedure in the coronary artery system has not been well investigated, with only occasional references in the literature.lv IS Only one series has demonstrated the variable degrees of myofibrointimal proliferation that occur at endarterectomy sites.P As a followup, the present study was undertaken to determine the antecedents of this response and to look at the sequential luminal/surface changes at endarterectomy sites at variable times after surgery.
Fromthe University ofOttawa Heart Institute, OttawaCivic Hospital, and the Departments of Pathology and Surgery, University of Ottawa,Ottawa,Ontario,Canada; and the Department of Histopathology, Adelaide Children's Hospital, North Adelaide, Australia.b Received for publication May I, 1990. Accepted for publication Oct. 22, 1990. Address for reprints: V. M. Walley, MD, Ottawa Civic Hospital, Department of Laboratory Medicine, 1053 CarlingAve., Ottawa, Ontario KIY 4E9, Canada. 12/1/26438
890
Materials and methods A retrospective study of consecutive autopsies at this institute, over a 2V2-year period, was undertaken to identify patients with a history of manual coronary endarterectomy and bypass grafting. Charts were reviewed and the patients were grouped into the following five categories according to the interval from operation to death: group A, up to 7 days; group B, 8 to 30 days; group C, 31 days to 6 months; group D, 6 months to 5 years; group E, more than 5 years. A detailed autopsy with particular emphasis on the cardiovascular system had been undertaken in each case. The heart had been fixed in 10% buffered formalin solution. Multiple histologic sections of myocardium were taken. The coronary arteries were removed en bloc. After decalcification in formic acid, the arteries were serially sectioned at 3 to 4 mm intervals. Sections of all major coronary arteries were taken, with the endarterectomized artery usually in toto. Endarterectomy sites were sampled extensively to include the native artery proximal and distal to the endarterectomy, the endarterectomized portion proximal and distal to the graft, and the vein graft. In particular, a standard area of the endarterectomy site was selected (distal to and shortly after the graft anastomosis) for electron microscopic examination. In some cases adjacent portions of vessel wall were also taken for electron microscopy. After standard processing, sections for light microscopy were cut at 4 /Lm and stained with hematoxylin, phloxine, and saffron and with Movat's pentachrome. Sections for transmission electron microscopy were postfixed in a solution of I% osmium tetroxide followed by a solution of 0.1% uranyl acetate for 1 hour before being embedded in Epon fixative. Examination was performed on a Phillips EM 201 electron microscope (Phillips Electronics, Sheldon, Conn.).
Volume 102
Number 6 December 1991
Coronary endarterectomy
891
Table I. Clinical features of 51 patients with coronary artery bypass grafting and manual endarterectomy (EA) Time after EA (days) Group
No.
A (0-7 days)
21
B (8-30 day)
6
C (31 days-6 mol
D (6--5 yr)
E (>5 yr)
6
4
17
Mean 1.6
19
56
785
3078
Age (yr)
Endarterectomized artery*
Range
Sex
Mean
Range
Artery
No.
0-7
3F IBM
59 60
56-66 41-71
RCA LAD D LM
14-30
2F 4M
65 64
64-66 62-75
RCA LAD D LM
12 7 3 2 24 4 2 I
40-78
255-1270
1851-3818
IF 2M
67 62
59-64
IF 3M
52 51
43-63
OF 17M
60
46-73
RCA LAD D LM RCA LAD D LM RCA LAD D LM
i
8 3 0 0 0 3 2 0 2 2 6 17 2 0 0 19
RCA, Right coronary artery; LAD, left anterior descending coronary artery; 0, diagonal branch of LAD; LM, marginal branch of left circumflex coronary artery. 'Note: Nine patients had more than one artery endarterectomized.
Sections were examined for luminal patency, thrombosis or clotting, perivascular hemorrhage or necrosis, perivascular inflammatory infiltrate, myofibrointimal proliferation, atherosclerosis, and any other significant histologic changes.
Results Clinical. A total of 60 endarterectomies were performed in the 51 patients, mainly in the right coronary artery (38 were right). There was a male preponderance of the patients (male/ female ratio = 44:7) and a mean age of 60 years (range 41 to 75). Results are summarized in Table 1. A clinical study to examine for any relationship that may exist between patient risk factors such as diabetes, hyperlipidermia and smoking, or medications,and the results of endarterectomy is in progress and will be reported separately. Pathologic. No differences in responses ofthe right coronary artery compared with the left were noted. Nineteen endarterectomy sites were found to have thrombosed in the immediate postoperative period: six in group A, two in group B, two in group C, three in group D, and six in group E. These vessels showed typical changes of thrombosis with organization eventually producing a fibrous plug in the collapsed lumen. In the remaining 41 patent vessels a continuum of histologic changes was seen. In group A, particularly those dying during or immediately after the operation, vesselsoften showed no sig-
nificant reaction. In these vessels the diseased intima had been neatly removed with virtually all the media, leaving external elastic lamina and adventitial tissues (Fig. 1, A). Thereafter, over the next few days, fibrin platelet mural thrombus or mixed mural thrombus could be expected on the denuded surfaces (Fig. 1, B). This thrombus organized by a process of vascularization and ingrowth of spindle cells (Fig. 1, C). Collagen deposition and reconstitution of a concentric and uniform luminal lining was accomplished by as little as 49 days (Fig. 1, D). Thereafter, this lining changed little, except that its cellularity decreased slightly and the amount of collagen and fine elastic fibers within it became more prominent (Fig. 1, E). Small foci of atherosclerosis were rarely seen in the oldest endarterectomized vessels (Fig. 1, F). The latter did not generally contribute to stenoses, which most often were related to the more typical concentric, but exaggerated, reparative response that was just described. In the immediate postoperative setting, endarterectomized vessels were diffusely mildly ectatic. The concentric healing process appeared in most instances to then reconstitute a vessel with normal-caliber lumen. In no instance was there evidence of aneurysm formation. Stenosis was found only in vessels from patients in group E (>5 years after endarterectomy), with 54% having mild-moderate stenosis and 46% having severe stenosis (>70% reduction in lumen area). Atheroma was a relatively insignificant feature
892
Walley, Byard, Keon
The Journal of Thoracic and Cardiovascular Surgery
Fig. 1. Photomicrographs of patent endarterectomized coronary arteries: A, on the first day, showing no reaction; B, at 6 days, with fibrin platelet thrombus on denuded surface; C, at 17 days, showing organization of thrombus with ingrowth of small vessels;D, at 49 days, with conversion of thrombus to dense collagen mixed with myofibrointimal cells; E, at 5 years, with dense myofibrointimal tissue incorporating fine elastic fibers; F, more than 5 years after the operation, with focal atheroma. (Movat's pentachromes, original magnifications X 160.)
found in groups D and E, contributing to stenosis in a minor degree in only four cases (25%). No significant perivascular hemorrhage, necrosis, or inflammatory infiltrates were found in any group. The results are summarized in Table II. Electron microscopic examination in the early postendarterectomy period demonstrated denuded media with exposed collagen fibers overlaid by thrombus composed of fibrin, plate-
lets, and red blood cells. Spindle-shaped cells having characteristic features of fibroblasts and small vessels were seen within organizing thrombi. Subsequently, similar spindle-shaped cells that contained irregular filaments and basal lamina characteristic of myofibroblasts were noted in a collagen background. These were first seen 4 weeks after the surgical procedure and were found in all subsequent sections after this period.
Volume 102 Number 6 December 1991
Coronary endarterectomy
893
Table II. Pathologic features of 41 patent endarterectomized coronary arteries at variable intervals after the operation* Group A (0-7 days)
No reaction Fibrin-platelet mural thrombus Mixed mural thrombus Organizing mural thrombus Myofibrointimal proliferation Without stenosis With mild stenosis With moderate stenosis With marked stenosis Atherosclerosis
B (8-30 days)
10/18 3/18 5/18
C
D
E
(31 days-6 rna)
(6 rno-5 yr)
(>5 yr)
1/1
3/3
1/6 1/6 2/6 2/6 2/13
1/3
5/13 6/13 3/13
'Note: Nineteen endarterectomy sites that were occluded immediately after the operation are not included in this analysis: 6 in A, 2 in B, 2 in C, 3 in D, and 6 in E.
Discussion A number of studies have demonstrated the healing response to manual endarterectomy within the carotid artery system, which involves proliferation of smooth muscle cells and connective tissue elements that probably originate in the media. 12, 16 Mural thrombi, in particular platelets, 'that are laid down over acutely traumatized surgical surfaces are believed to be important stimuli to the reparative response.F' 16, 17 Interestingly, aspirin and other antiplatelet agents do not appear to decrease the prevalence of the more exuberant cases of such proliferation that are responsible for many of the cases of restenosis.P: 16 Myointimal proliferation in endarterectomized carotid arteries is known to produce stenoses in the short term ( <2 years) and perhaps to be the background of the atherosclerosis that is believed responsible for those stenoses that develop over the long term. 6- 13 In a previous study of long-term survivors (>5 years) of coronary endarterectomy, a similar myofibrointimal reparative response at the site of the operation was observed. IS This response was almost always concentric and uniform. In contrast to carotid endarterectomy, it was this feature that was found to be responsible for late stenosis, with little contribution from recurrent atherosclerosis, which occurred infrequently and usually only focally to a minor degree. Of interest, severe stenosis in these endarterectomized vessels was unusual and was seen only in those patients who had been operated on 5 years earlier. The present broader study, which was undertaken to further delineate the sequential morphologic changes within endarterectomized coronary arteries, indicates
that the initial change in a vessel that remains patent is mural thrombus deposition with only a minimal acute surrounding inflammatory reaction. This is followed by organization of the thrombus with capillary ingrowth and fibroblast proliferation. Myofibroblasts with increasing amounts of collagen and elastic fiber deposition are then found. Electron microscopic examination of vessels at various times after endarterectomy confirms the nature of the spindle cells, which show features characteristic of myofibroblasts. Whether these cells represent locally transformed cells or migrating cells from the adjacent nonendarterectomized media is not possible to ascertain from the results. Studies examining the origin of neointima in synthetic grafts suggest that local transformation of the responsible cellular elements and their growth through the graft interstices is important in the intimal healing in that setting.l" This may explain why intimal healing can occur simultaneously along the length of the graft, an observation that also appears true in the setting of endarterectomy as described here. Alternatively, seeded circulating white cells may serve as the source of portions of the proliferating cellular elements.P' 19 In conclusion, this study was undertaken to demonstrate the sequence of morphologic changes that occurs in endarterectomized coronary arteries. In vessels that remain patent after the operation, initial mural thrombus deposition is followed by organization and myofibrointimal proliferation, which may eventually result in stenosis with focal atherosclerosis. This demonstration of the morphologic changes provides histopathologic correlation for features that have been shown angiographically.20-22
The Journal of
894
Walley, Byard, Keon
We thank Jennifer Calleja, Norah Burton, and Leslie O'Connor for typing the manuscript and Dr. Feroze Ghadially for review of the electron micrographs. REFERENCES I. Livesay JJ, Cooley DA, Hallman GL, et a!. Early and late results of coronary endarterectomy. J THORAC CARDIOVASC SURG 1986;9:649-57. 2. Walter PJ, Armbruster M, Amsel BJ, Scheld HH. Endarterectomy in patients with diffuse coronary artery disease. In: Walter PJ, ed. Treatment of end stage coronary artery diseases. Adv Cardio!. Basel: Karger, 1988;36:41-53. 3. Livesay JJ. Summary: treatment of diffuse coronary artery disease by endarterectomy. In: Walter PJ, ed. Treatment of end stage coronary artery diseases. Adv Cardio!. Basel: Karger, 1988;36:71-3. 4. Livesay JJ, Cooley DA, Duncan JM, et al. Early and late results of coronary endarterectomy in 3,369 patients. In: Walter PJ, ed. Treatment of end stage coronary artery diseases. Adv Cardio!. Basel: Karger, 1988;36:27-33. 5. Loop FD. Resurgence of coronary artery endarterectomy. J Am Coli CardioI1988;11:712-3. 6. Thomas M, Otis SM, Rush M, Zyroff J, Dilley RB, Bernstein EF. Recurrent carotid artery stenosis followingendarterectomy. Ann Surg 1984;200:74-9. 7. Das MB, Hertzer NR, RatliffNB, O'Hara PJ, Beven EG. Recurrent carotid stenosis. Ann Surg 1985;202:28-35. 8. Clagett GP, Robinowitz M, Youkey JR, et al. Morphogenesis and clinicopathologic characteristics of recurrent carotid disease. J Vase Surg 1986;3:10-23. 9. Imparato AM, Weinstein GS. Clinicopathologic correlation in postendarterectomy recurrent stenosis:a case report and bibliographic review. J Vase Surg 1986;3:657-62. 10. Piepgras DG, Sundt TM, Marsh WR, Mussman LA, Fode NC. Recurrent carotid stenosis: results and complications of 57 operations. Ann Surg 1986;203:205-13. II. Shumway SJ, Edwards WH, Jenkins JM, Mulhern JL, Edwards WH Jr. Recurrent carotid stenosis:incidence and management. Am Surg 1987;53:61-5.
Thoracic and Cardiovascular Surgery
12. Schwarcz TH, Yates GN, Ghobrial M, Baker WHo Pathologic characteristics of recurrent carotid artery stenosis. J Vase Surg 1987;5:208-8. 13. Clagett GP, Rich NM, McDonald PT, et a!. Etiologic factors for recurrent carotid artery stenosis. Surgery 1983;93: 313-8. 14. Kragel AH, McIntosh CM, Roberts WC. Morphologic changes in coronary artery seen late after endarterectomy. Am J CardioI1989;63:757-9. 15. Byard RW, Keon WJ, Walley VM. Coronary endarterectomy: the long term local effects. Am J Cardiovasc Pathol 1988;2:31-8. 16. Bush HL Jr, Jakubowski JA, Sentissi JM, Curl GR, Hayes JA, Deykin D. Neointimal hyperplasia occurring after carotid endarterectomy in a canine model: effect of endothelial cell seeding vs. perioperative aspirin. J Vase Surg 1987;5:118-25. 17. Clowes AW, Clowes MM, Reidy MA. Kinetics of cellular proliferation after arterial injury. III. Endothelial and smooth muscle growth in chronically denuded vessels. Lab Invest 1986;54:295-303. 18. Greisler HP, Dennis JW, Endeau ED, Ellinger J, Buttle KF, Kim DU. Derivation of neointima in vascular grafts. Circulation 1988;78(Pt 2):16-12. 19. Stump MM, Jordan GL, DeBakey ME, Halpert B. Endothelium grown from circulating blood on isolated intravascular Dacron hub. Am J PathoI1963;43:361-7. 20. Keon WJ, Hendry P, Boyd WD, Walley VM. Long-term follow-up of coronary endarterectomy. In: Walter PJ, ed. Treatment of end stage coronary artery diseases. Adv Cardio!. Basel: Karger, 1988;36:19-26. 21. Ivert T, Welti R, Forssell G, Landou C. Coronary endarterectomy-angiographic and clinical results. Scand J Thorac Cardiovasc Surg 1989;23:95-102. 22. Brenowitz JB, Kayser KL, Johnson WD. Results of coronary artery endarterectomy and reconstruction. J THORAC CARDIOVASC SURG 1988;95:1-10.
A study of the sequential morphologic changes after manual coronary endarterectomy Manual coronary endarterectomies heal in the long-term by a poorly understood process of myofibrointimal proliferation. A retrospective analysis of detailed cardiovascular pathologic examinations of 51 patients dying at varying intervals after endarterectomy provides insight into the sequence of this proliferative response. Twenty-one patients died within 7 days, 6 at 8 to 30 days, 3 at 31 days to 6 months, 4 at 6 months to 5 years, and 17 at more than 5 years after endarterectomy. The observations made suggest that the denuded arterial surface heals after the fibrin-platelet mural thrombus that covers it is organized and is replaced by fibrosis and myofibroblast proliferation. In unusual cases proliferation is exuberant, resulting in significant restenosis, an outcome in which recurrent atherosclerosis contributes to only a minor degree. This is the first series in which the sequential reparative changes at varying times after manual coronary endarterectomy have been studied.
V. M. Walley, MD,a R. W. Byard, MBBS,b and W. J. Keon, MD,a Ottawa, Ontario. Canada. and North Adelaide, Australia
Coronary endarterectomy performed at the time of bypass grafting enables otherwise diffusely diseased and inoperable arteries to be grafted. 1 The procedure is most often done manually.l? Although the reaction to carotid endarterectomy has been previously well documented.vP the response to this procedure in the coronary artery system has not been well investigated, with only occasional references in the literature.lv IS Only one series has demonstrated the variable degrees of myofibrointimal proliferation that occur at endarterectomy sites.P As a followup, the present study was undertaken to determine the antecedents of this response and to look at the sequential luminal/surface changes at endarterectomy sites at variable times after surgery.
Fromthe University ofOttawa Heart Institute, OttawaCivic Hospital, and the Departments of Pathology and Surgery, University of Ottawa,Ottawa,Ontario,Canada; and the Department of Histopathology, Adelaide Children's Hospital, North Adelaide, Australia.b Received for publication May I, 1990. Accepted for publication Oct. 22, 1990. Address for reprints: V. M. Walley, MD, Ottawa Civic Hospital, Department of Laboratory Medicine, 1053 CarlingAve., Ottawa, Ontario KIY 4E9, Canada. 12/1/26438
890
Materials and methods A retrospective study of consecutive autopsies at this institute, over a 2V2-year period, was undertaken to identify patients with a history of manual coronary endarterectomy and bypass grafting. Charts were reviewed and the patients were grouped into the following five categories according to the interval from operation to death: group A, up to 7 days; group B, 8 to 30 days; group C, 31 days to 6 months; group D, 6 months to 5 years; group E, more than 5 years. A detailed autopsy with particular emphasis on the cardiovascular system had been undertaken in each case. The heart had been fixed in 10% buffered formalin solution. Multiple histologic sections of myocardium were taken. The coronary arteries were removed en bloc. After decalcification in formic acid, the arteries were serially sectioned at 3 to 4 mm intervals. Sections of all major coronary arteries were taken, with the endarterectomized artery usually in toto. Endarterectomy sites were sampled extensively to include the native artery proximal and distal to the endarterectomy, the endarterectomized portion proximal and distal to the graft, and the vein graft. In particular, a standard area of the endarterectomy site was selected (distal to and shortly after the graft anastomosis) for electron microscopic examination. In some cases adjacent portions of vessel wall were also taken for electron microscopy. After standard processing, sections for light microscopy were cut at 4 /Lm and stained with hematoxylin, phloxine, and saffron and with Movat's pentachrome. Sections for transmission electron microscopy were postfixed in a solution of I% osmium tetroxide followed by a solution of 0.1% uranyl acetate for 1 hour before being embedded in Epon fixative. Examination was performed on a Phillips EM 201 electron microscope (Phillips Electronics, Sheldon, Conn.).
Volume 102
Number 6 December 1991
Coronary endarterectomy
891
Table I. Clinical features of 51 patients with coronary artery bypass grafting and manual endarterectomy (EA) Time after EA (days) Group
No.
A (0-7 days)
21
B (8-30 day)
6
C (31 days-6 mol
D (6--5 yr)
E (>5 yr)
6
4
17
Mean 1.6
19
56
785
3078
Age (yr)
Endarterectomized artery*
Range
Sex
Mean
Range
Artery
No.
0-7
3F IBM
59 60
56-66 41-71
RCA LAD D LM
14-30
2F 4M
65 64
64-66 62-75
RCA LAD D LM
12 7 3 2 24 4 2 I
40-78
255-1270
1851-3818
IF 2M
67 62
59-64
IF 3M
52 51
43-63
OF 17M
60
46-73
RCA LAD D LM RCA LAD D LM RCA LAD D LM
i
8 3 0 0 0 3 2 0 2 2 6 17 2 0 0 19
RCA, Right coronary artery; LAD, left anterior descending coronary artery; 0, diagonal branch of LAD; LM, marginal branch of left circumflex coronary artery. 'Note: Nine patients had more than one artery endarterectomized.
Sections were examined for luminal patency, thrombosis or clotting, perivascular hemorrhage or necrosis, perivascular inflammatory infiltrate, myofibrointimal proliferation, atherosclerosis, and any other significant histologic changes.
Results Clinical. A total of 60 endarterectomies were performed in the 51 patients, mainly in the right coronary artery (38 were right). There was a male preponderance of the patients (male/ female ratio = 44:7) and a mean age of 60 years (range 41 to 75). Results are summarized in Table 1. A clinical study to examine for any relationship that may exist between patient risk factors such as diabetes, hyperlipidermia and smoking, or medications,and the results of endarterectomy is in progress and will be reported separately. Pathologic. No differences in responses ofthe right coronary artery compared with the left were noted. Nineteen endarterectomy sites were found to have thrombosed in the immediate postoperative period: six in group A, two in group B, two in group C, three in group D, and six in group E. These vessels showed typical changes of thrombosis with organization eventually producing a fibrous plug in the collapsed lumen. In the remaining 41 patent vessels a continuum of histologic changes was seen. In group A, particularly those dying during or immediately after the operation, vesselsoften showed no sig-
nificant reaction. In these vessels the diseased intima had been neatly removed with virtually all the media, leaving external elastic lamina and adventitial tissues (Fig. 1, A). Thereafter, over the next few days, fibrin platelet mural thrombus or mixed mural thrombus could be expected on the denuded surfaces (Fig. 1, B). This thrombus organized by a process of vascularization and ingrowth of spindle cells (Fig. 1, C). Collagen deposition and reconstitution of a concentric and uniform luminal lining was accomplished by as little as 49 days (Fig. 1, D). Thereafter, this lining changed little, except that its cellularity decreased slightly and the amount of collagen and fine elastic fibers within it became more prominent (Fig. 1, E). Small foci of atherosclerosis were rarely seen in the oldest endarterectomized vessels (Fig. 1, F). The latter did not generally contribute to stenoses, which most often were related to the more typical concentric, but exaggerated, reparative response that was just described. In the immediate postoperative setting, endarterectomized vessels were diffusely mildly ectatic. The concentric healing process appeared in most instances to then reconstitute a vessel with normal-caliber lumen. In no instance was there evidence of aneurysm formation. Stenosis was found only in vessels from patients in group E (>5 years after endarterectomy), with 54% having mild-moderate stenosis and 46% having severe stenosis (>70% reduction in lumen area). Atheroma was a relatively insignificant feature
892
Walley, Byard, Keon
The Journal of Thoracic and Cardiovascular Surgery
Fig. 1. Photomicrographs of patent endarterectomized coronary arteries: A, on the first day, showing no reaction; B, at 6 days, with fibrin platelet thrombus on denuded surface; C, at 17 days, showing organization of thrombus with ingrowth of small vessels;D, at 49 days, with conversion of thrombus to dense collagen mixed with myofibrointimal cells; E, at 5 years, with dense myofibrointimal tissue incorporating fine elastic fibers; F, more than 5 years after the operation, with focal atheroma. (Movat's pentachromes, original magnifications X 160.)
found in groups D and E, contributing to stenosis in a minor degree in only four cases (25%). No significant perivascular hemorrhage, necrosis, or inflammatory infiltrates were found in any group. The results are summarized in Table II. Electron microscopic examination in the early postendarterectomy period demonstrated denuded media with exposed collagen fibers overlaid by thrombus composed of fibrin, plate-
lets, and red blood cells. Spindle-shaped cells having characteristic features of fibroblasts and small vessels were seen within organizing thrombi. Subsequently, similar spindle-shaped cells that contained irregular filaments and basal lamina characteristic of myofibroblasts were noted in a collagen background. These were first seen 4 weeks after the surgical procedure and were found in all subsequent sections after this period.
Volume 102 Number 6 December 1991
Coronary endarterectomy
893
Table II. Pathologic features of 41 patent endarterectomized coronary arteries at variable intervals after the operation* Group A (0-7 days)
No reaction Fibrin-platelet mural thrombus Mixed mural thrombus Organizing mural thrombus Myofibrointimal proliferation Without stenosis With mild stenosis With moderate stenosis With marked stenosis Atherosclerosis
B (8-30 days)
10/18 3/18 5/18
C
D
E
(31 days-6 rna)
(6 rno-5 yr)
(>5 yr)
1/1
3/3
1/6 1/6 2/6 2/6 2/13
1/3
5/13 6/13 3/13
'Note: Nineteen endarterectomy sites that were occluded immediately after the operation are not included in this analysis: 6 in A, 2 in B, 2 in C, 3 in D, and 6 in E.
Discussion A number of studies have demonstrated the healing response to manual endarterectomy within the carotid artery system, which involves proliferation of smooth muscle cells and connective tissue elements that probably originate in the media. 12, 16 Mural thrombi, in particular platelets, 'that are laid down over acutely traumatized surgical surfaces are believed to be important stimuli to the reparative response.F' 16, 17 Interestingly, aspirin and other antiplatelet agents do not appear to decrease the prevalence of the more exuberant cases of such proliferation that are responsible for many of the cases of restenosis.P: 16 Myointimal proliferation in endarterectomized carotid arteries is known to produce stenoses in the short term ( <2 years) and perhaps to be the background of the atherosclerosis that is believed responsible for those stenoses that develop over the long term. 6- 13 In a previous study of long-term survivors (>5 years) of coronary endarterectomy, a similar myofibrointimal reparative response at the site of the operation was observed. IS This response was almost always concentric and uniform. In contrast to carotid endarterectomy, it was this feature that was found to be responsible for late stenosis, with little contribution from recurrent atherosclerosis, which occurred infrequently and usually only focally to a minor degree. Of interest, severe stenosis in these endarterectomized vessels was unusual and was seen only in those patients who had been operated on 5 years earlier. The present broader study, which was undertaken to further delineate the sequential morphologic changes within endarterectomized coronary arteries, indicates
that the initial change in a vessel that remains patent is mural thrombus deposition with only a minimal acute surrounding inflammatory reaction. This is followed by organization of the thrombus with capillary ingrowth and fibroblast proliferation. Myofibroblasts with increasing amounts of collagen and elastic fiber deposition are then found. Electron microscopic examination of vessels at various times after endarterectomy confirms the nature of the spindle cells, which show features characteristic of myofibroblasts. Whether these cells represent locally transformed cells or migrating cells from the adjacent nonendarterectomized media is not possible to ascertain from the results. Studies examining the origin of neointima in synthetic grafts suggest that local transformation of the responsible cellular elements and their growth through the graft interstices is important in the intimal healing in that setting.l" This may explain why intimal healing can occur simultaneously along the length of the graft, an observation that also appears true in the setting of endarterectomy as described here. Alternatively, seeded circulating white cells may serve as the source of portions of the proliferating cellular elements.P' 19 In conclusion, this study was undertaken to demonstrate the sequence of morphologic changes that occurs in endarterectomized coronary arteries. In vessels that remain patent after the operation, initial mural thrombus deposition is followed by organization and myofibrointimal proliferation, which may eventually result in stenosis with focal atherosclerosis. This demonstration of the morphologic changes provides histopathologic correlation for features that have been shown angiographically.20-22
The Journal of
894
Walley, Byard, Keon
We thank Jennifer Calleja, Norah Burton, and Leslie O'Connor for typing the manuscript and Dr. Feroze Ghadially for review of the electron micrographs. REFERENCES I. Livesay JJ, Cooley DA, Hallman GL, et a!. Early and late results of coronary endarterectomy. J THORAC CARDIOVASC SURG 1986;9:649-57. 2. Walter PJ, Armbruster M, Amsel BJ, Scheld HH. Endarterectomy in patients with diffuse coronary artery disease. In: Walter PJ, ed. Treatment of end stage coronary artery diseases. Adv Cardio!. Basel: Karger, 1988;36:41-53. 3. Livesay JJ. Summary: treatment of diffuse coronary artery disease by endarterectomy. In: Walter PJ, ed. Treatment of end stage coronary artery diseases. Adv Cardio!. Basel: Karger, 1988;36:71-3. 4. Livesay JJ, Cooley DA, Duncan JM, et al. Early and late results of coronary endarterectomy in 3,369 patients. In: Walter PJ, ed. Treatment of end stage coronary artery diseases. Adv Cardio!. Basel: Karger, 1988;36:27-33. 5. Loop FD. Resurgence of coronary artery endarterectomy. J Am Coli CardioI1988;11:712-3. 6. Thomas M, Otis SM, Rush M, Zyroff J, Dilley RB, Bernstein EF. Recurrent carotid artery stenosis followingendarterectomy. Ann Surg 1984;200:74-9. 7. Das MB, Hertzer NR, RatliffNB, O'Hara PJ, Beven EG. Recurrent carotid stenosis. Ann Surg 1985;202:28-35. 8. Clagett GP, Robinowitz M, Youkey JR, et al. Morphogenesis and clinicopathologic characteristics of recurrent carotid disease. J Vase Surg 1986;3:10-23. 9. Imparato AM, Weinstein GS. Clinicopathologic correlation in postendarterectomy recurrent stenosis:a case report and bibliographic review. J Vase Surg 1986;3:657-62. 10. Piepgras DG, Sundt TM, Marsh WR, Mussman LA, Fode NC. Recurrent carotid stenosis: results and complications of 57 operations. Ann Surg 1986;203:205-13. II. Shumway SJ, Edwards WH, Jenkins JM, Mulhern JL, Edwards WH Jr. Recurrent carotid stenosis:incidence and management. Am Surg 1987;53:61-5.
Thoracic and Cardiovascular Surgery
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