Comparative anatomic studies of various arterial conduits for myocardial revascularization

J

THoRAc CARDIOVASC SURG

1990;99:703-7

Comparative anatomic studies of various arterial conduits for myocardial revascularization Comparison was made between the morphologic condition of the left anterior descending artery and four arterial conduits: the internal mammary, right gastroepiploic, inferior epigastric, and radial arteries, harvested from 17 patients (aged 15 to 85 years, mean 64 years) who had died of nonvascular diseases. Proximal, mid, and distal segments were examined microscopicaDy. The internal mammary artery was elastic, but the others were muscular. In aD four conduits, atherosclerosis was absent to mild, the internal elastic lamina showed only minimal defects, and the vasa vasorum were confined to the adventitia. In aD cases the left anterior descending artery showed mild to severe atherosclerosis and substantial defects in the internal elastic lamina with penetration of the vasa vasorum into the media and intima. Comparison of the mean distance (± standard deviation) from the lumen to the outermost portion of the media for the left anterior descending artery (320 ± 63 J.Lm) with the four conduits gave comparable values for the internal mammary artery (350 ± 92 J.Lm); p = not significant) and the right gastroepiploic artery (291 ± 109 J.Lm; p = not signitlcant), versus 529 ± 52 J.Lm; p < 0.002) for the radial artery and 249 /.Lm (± 87 /.Lm) (p < 0.04) for the inferior epigastric artery (Kruskal-Wallis and Mann-Whitney U tests). The relatively scanty presence of smooth muscle ceUs in the thin-waDed media of the internal mammary artery combined with a weD-formed internal elastic lamina, even at advanced age, may be an important cause for its low susceptibility to atherosclerosis and a major determinant in its superior long-term patency as a coronary artery bypass graft. This fillding emphasizes the justification of continued use of the ideaDy matching internal mammary artery, either as in situ or free graft, in coronary artery bypass grafting. In contrast to the thick-waDed radial artery, which may be relatively prone to ischemia, an acceptable long-term patency of the inferior epigastric artery and right gastroepiploic artery, if harvested as pedicled grafts, is anticipated.

Jacques A. M. van Son, MD, Frank Smedts, MD, Josef G. Vincent, MD, Henk J. J. van Lier, MSc, and Karel Kubat, MD, Nijmegen, The Netherlands

Expanded use of the internal mammary artery (IMA) for myocardial revascularization is based on accumulating data of superior late patency of the IMA compared with venous conduits. 1-8 The primary consideration that has led to the gradual transition of use of the IMA as the conduit of choice is its relative freedom from atheroscle-

From the Departments of Thoracic and Cardiac Surgery, Pathology, and Statistical Consultation, Academic Hospital Nijrnegen, Nijmegen, The Netherlands. Received for publication March 13, 1989. Accepted for publication June 16, 1989. Address for reprints: Jacques A.M. van Son, MD, Department of Thoracic and Cardiac Surgery, Academic Hospital N ijrnegen, P.O. Box 9101.6500 HB Nijmegen, The Netherlands.

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rosis with follow-up to 10 years and beyond. As the frequency of coronary revascularization procedures has increased in patients with diseased or absent greater and lesser saphenous veins, alternatives to this arterial conduit have been sought. Recently the right gastroepiploic artery (RGEA) has been described as an alternative bypass graft to coronary vessels on the posterior surface of the heart." We advocate use of the inferior epigastric artery (lEA) as another alternative arterial conduit when traditional conduits are unsuitable. The radial artery (RA) has been used in the past as a conduit in aorta-coronary bypass surgery, but has been abandoned because of its high failure rate.!" This article describes histologic studies of the left anterior descending artery (LAD) and four arterial conduits: the IMA, RGEA, lEA, and RA. The purpose of this study was to define certain anatomic similarities and 703

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van Son et al.

Surgery

Fig. 1. Examples of four arterial conduits. The IMA (C) is an elastic artery, whereas the lEA (A), RGEA (B), and RA (D) are muscular. Note the fenestrations in the internal elastic lamina (arrows). The combined width of intima and media increases from left to right. (Elastin-trichrome after Masson stain; original magnification X 140.)

Table I. Combined width of intima and media in LAD and various arterial conduits* Width of intima and media (± SD) [urn} Arteries (n= 17)

LAD

IMA RGEA lEA RA

Fixation in flaccid state 320 350 291 249 529

Fixation at pressure of 100 mm Hg

± 63

± 92 ± 109 ± 87

313 ± 209 303 ± 100 284 ± 136

± 52

*Kruskal-Wallis analysis of variance.

dissimilarities among these arteries and correlate these to their proved or anticipated long-term patency as coronary bypass grafts. Material and methods The material for this study was obtained at autopsy from 17 unselected individuals, between 15 and 85 years of age (mean 64 years), who died of nonvascular diseases. The study material consistedofthe LAD, IMA, RGEA, lEA, and RA. Taking into account possible artifacts in diameters of the arterial wall as a result of fixation in a flaccid state, we also fixed arteries at their normal mean physiologic pressure: In II cases the IMA, RGEA, and lEA were fixed in a flaccid state in 4% formaldehyde solution before further processing, whereas in six cases

these arteries were subjected to hydrostatic dilation by connecting the proximal ends of the arteries to a column of 4% formaldehyde solution at a pressure of 100 mm Hg. After the formaldehyde solution had been allowed to flow through the arteries for a few minutes to remove any air in the vessels, the distal ends and branches were ligated. Subsequently the arteries were fixed at a pressure of 100 mm Hg for 4 hours. The LAD and RA specimens were all fixed in a flaccid state. Transverse sections with a thickness of 10 Jlm were stained by the following methods: hematoxylin-eosin, elastin-trichrome after Masson, alcian blue at pH 2.8, and immunostaining for factor VIII. In multiple transverse sections the combined width of intima and media was measured at four random locations per section.

Results In all cases the IMA showed the typical structure of an elastic artery with 9 to 12 elastic lamellae in the media, including the internal and external elastic laminae. Smooth muscle cells and collagen are dispersed between the elastic lamellae. The LAD, RGEA, IEA, and RA are muscular arteries, the media of which consist of smooth muscle cells and are limited by the internal and external elastic laminae (Figs. 1 and 2). Statistical analysis (Kruskal-Wallis and Mann-Whitney U tests) showed no significant differences in the mean combined width of the intima and media in the LAD, IMA, and RGEA, contrasting a greater and smaller width in the RA and the

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Arterial conduits for myocardial revascularization 7 0 5

Fig.. 2. A, Example of an atherosclerotic LAD. (Elastin-trichrome after Masson stain, original magnification X35.) B, Vascularization of the intima with local destruction of the internal elastic lamina (arrow) and medial degeneration with fibrosis. (Elastin-trichrome after Masson stain; original magnification X350.)

lEA, respectively (Tables I and II). There was no significant difference in the combined width of intima and media in arteries fixed in a flaccid state or at a pressure of 100 mm Hg (Table I). In all cases the LAD showed moderate to severe atherosclerosis, substantial defects in the internal elastic lamina, and penetration of the vasa vasorum into the media or intima and media, corresponding to the severity of the atherosclerosis (Fig. 2). In contrast, atherosclerosis was absent or only mildly present in all four arterial conduits; the internal elastic lamina showed only minimal defects and the vasa vasorum were confined to the adventitia.

Discussion Over the long term, there is a striking difference in the late development of atherosclerosis in IMA bypass conduits compared with venous conduits. Comparison of IMA and vein graft patency reveals a highly significant difference at every interval? Accelerated vein graft closure because of progressive intimal hyperplasia and atherosclerosis begins in the fifth year and approximates 5%per year, with a 1O-yearpatency rate varying between 41% and 56%.3 In contrast, the 1O-yearIMA patency rate has been reported to be greater than 80%.3.7 It is intrigu-

Table II. Significant p values concerning combined width of intima and media among LAD and various arterial conduits" Arteries

p Value

RA-LAD RA-IMA RA-RGEA RA-IEA LAD-lEA IMA-IEA

0.002 0.002 0.0003 0.0003 0.04 0.02

* Mann- Whitney

U lest.

ing that the IMA, a vessel comparable in cross-sectional diameter to the coronary artery and acclimated to the same arterial hemodynamics, intrathoracic respiratory pressure changes, and biochemical environment, has such a low incidence of atherosclerosis. Although the cause of the apparent protection of the IMA from intimal thickening and atherosclerosis remains obscure, a few comments can be made on the basis of our study and accumulated evidence from research in vascular pathology. The systemic arteries serve as a pressure reservoir by means of the elastic properties of their walls. The ascend-

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van Son et al.

ing aorta functions as a type of surge chamber immediately downsteam from the left ventricle. In a large series of autopsies, we observed a gradual decrease of the diameter of the media downstream from the aorta ascendens, which was primarily related to a corresponding decrease in packing density of elastic fibers in the media. Conversely, the diameter of the aortic intima gradually increased from proximal to distal; this finding issupported by others. 11.12 A similar gradual decrease of elastic fibers in the media was found along the downstream course of the IMA, albeit that IMA specimens in our study, even when harvested beyond the epigastric bifurcation, retained their elastic character. In an examination by Geiringer 13of 300 aortas and 100 LADs, all in a moderately to severely atherosclerotic state, the critical depth beyond which intimal vascularization by the vasa vasorum made its appearance was found to be approximately 500 /-Lm for the aorta and approximately 350 /-Lm for the first inch of the LAD. In our study we found vascularization of the media, or intima and media, in all atherosclerotically diseased LADs, also below the critical thickness as mentioned by Geiringer. Both a histologic study by Landymore and Chapman 14 and our study were unable to demonstrate any vascularization of the media by vasa vasorum in the IMA. In addition, we found that the vasa vasorum were confined to the adventitia in the RGEA, lEA, and RA, contrasting the presence of vasa vasorum in the media or media and intima in all atherosclerotic LAD specimens. Histologic research has established that the first stage of intimal thickening is caused by invasion of smooth muscle cells from the media through the fenestrated internal elastic lamina.P In the first decade of life this intimal thickening can already be observed. Sims 16 , 17 pointed out that the internal elastic lamina has a key role in arterial wall structure. His observations suggest that the occurrence of discontinuities in the internal elastic lamina provokes early and progressive intimal hyperplasia. Stimuli that trigger smooth muscle cell proliferation are most likely complex and may include leakage of blood constituents and exertion of stress forces on the smooth muscle cells." Operation of these processes over a long period may contribute to progressive intimal hyperplasia. If, as the accumulated evidence suggests, damage to the internal elastic lamina in the presence of smooth muscle cells in the media has a determining role in the initiation of intimal thickening, as a result of the proliferation of smooth muscle cells from the media, it is intriguing to consider that elastic arteries may be less prone to intimal hyperplasia than muscular arteries. In the former, intimal hyperplasia develops at a considerably delayed rate because proliferative smooth muscle cells are present only

The Journal of Thoracic and Cardiovascular Surgery

to a moderate extent. In addition, the multiple elastic lamellae and the internal elastic lamina form barriers to their invasion. Moreover, elastin, the basic component of the elastic tissue of the media, is a bradytrophic, relatively inert tissue with a low metabolic rate. It therefore has a lower intrinsic demand for oxygen and substrates, either by diffusion from the main lumen or by perfusion by the vasa vasorum, than the compact media of the muscular artery. A third factor that may lead to delayed onset of intimal hyperplasia in the IMA compared with the coronary artery is an abundant lymphatic drainage of the IMA, contrasting a marginal one of the coronary artery. 19 The data just presented may have important repercussions with regard to the long-term patency rate of various arterial conduits in aorta-coronary bypass surgery. The IMA has proved to be relatively resistant to intimal hyperplasia and atherosclerosis, which may have its cause in the aforementioned histologic features. A reported patency rate of free, pedicled IMA grafts approximating that of in situ IMA grafts'? is consistent with our supposition that the IMA is nourished entirely from the lumen. Any discrepancy in patency rate between in situ and free IMA grafts may be attributable primarily to the proximal anastomosis. Stripping of the adventitia from the thinwalled IMA may create areas of intimal disruption, leading to medial necrosis, intimal hyperplasia, and ultimately fibrosis." It follows that extension of the use of the IMA through bilateral and sequential grafting 7, 22-25 would improve already excellent long-term patency rates that could be obtained by particularly gentle surgical techniques and continuing refinement of sutures and microsurgical instruments. Thus minimization of disruption of the internal elastic lamina could reduce intimal hyperplasia and atherosclerosis. The ideally matching calibers of IMA and LAD may minimize the occurrence of turbulences, and secondarily thrombosis, at the anastomotic site, which may be another cause of the low occlusion rate of the IMA conduit. Accelerated intimal hyperplasia, as encountered in RA grafts, may in retrospect have been the result primarily of focal damage to the intima, both by dilation of the vessel with graduated probes and by stripping of the vessel of surrounding tissue. 10 Focal damage to the internal elastic lamina may trigger a cascade of events as previously described and may ultimately lead to progressive proliferation and migration of smooth muscle cells into the intima. A second factor that has been incriminated in the development of intimal hyperplasia in the RA conduit is ischemia, reportedly caused by deprivation of its vasa vasorum and lymphatic drainage. Ischemia may have been a cause, although we could not demonstrate any penetration of vasa vasorum into the media of the RA.

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There are only occasional reports of long-term patency of gastroepiploic conduits with regard to the patency rate ofthe RGEA.9 On the basis of our comparative histologic study, we speculate that the RGEA and lEA conduits may yield an enhanced long-term patency rate in comparison with the RA conduit. This expectation is derived from our observation that the latter has a considerably thicker media and thus may be more prone to ischemia. Acceptable long-term patency rates of RGEA and lEA conduits may be anticipated when proper techniques are used. It is of paramount importance to create pedicled grafts, thus avoiding intimal disruption and accelerated intimal hyperplasia. REFERENCES I. Lytle BW, Loop FD, Cosgrove OM, RatliffNB, Easley K, Taylor Pc. Long-term (5 to 12 years) serial studies of internal mammary artery and saphenous vein coronary bypass grafts. J THORAC CARDIOVASC SURG 1985;89:248. 58. 2. Loop FD, Lytle BW, Cosgrove OM, et al. Influence of the internal-mammary-artery-graft on lO-year survival and other cardiac events. N Engl J Med 1986;314:1-6. 3. Grondin CM, Campeau L, Lesperance J, Enjalbert M, Bourassa MG. Comparison of late changes in internal mammary artery and saphenous vein grafts in two consecutive series of patients 10 years after operation. Circulation 1984;70(Pt 2):1208-12. 4. Campeau L, Enjalbert M, Lesperance J, et al. The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation: a study 10 years after aorto-coronary bypass surgery. N Engl J Med 1984;311:1329-32. 5. Tector AJ, Schmahl TM, Janson B, Kal1ies JR, Johnson G. The internal mammary artery graft: its longevity after coronary bypass. JAMA 1981;246:2181-3. 6. Tector AJ. Fifteen years' experience with the internal mammary artery graft. Ann Thorac Surg 1986;42 (suppl):22-7. 7. Barner HB, Swartz MT, Mudd JG, Tyras DH. Late patency of the internal mammary artery as a coronary bypass conduit. Ann Thorac Surg 1982;34:408-12. 8. Ivert T, Huttunen K, Landou C, Bjork VO. Angiographic studies of internal mammary artery grafts II years after coronary artery bypass grafting. J THORAC CARDIOVASC SURG 1988;96:1-12. 9. Pym J, Brown PM, Charrette EJP, Parker JO, West RO. Gastroepiploic-coronary anastomosis: a viable alternative bypass graft. J THORAC CARDIOVASC SURG 1987;94: 256-9.

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10. Curtis JJ, Stoney WS, Alford WC Jr, BurrusGR, Thomas CS Jr. Intimal hyperplasia: a cause of radial artery aortacoronary bypass graft failure. Ann Thorac Surg 1975; 20:628-35. II. Jores L. Arterien. In: Henke F, Lubarsch 0, eds. Handbuch der Speziel1en Pathologischen Anatomie und Histologie, vol II: Herz und Gefiisse. 1st ed. Berlin: J Springer, 1924:608-786. 12. Movat HZ, More RH, Haust MD. The diffuse intimal thickening of the human aorta with aging. Am J Pathol 1958;34:1023-31. 13. Geiringer E. Intimal vascularisation and atherosclerosis. J Pathol Bacteriol 1951;63:201-11. 14. Landymore RW, Chapman OM. Anatomical studies to support the expanded use of the internal mammary artery graft for myocardial revascularization. Ann Thorac Surg 1987;44:4-6. 15. Ross R, Glomset JA. The pathogenesis of atherosclerosis. N Engl J Med 1976;295:369-76, 420-5. 16. Sims FH. A comparison of coronary and internal mammary arteries and implications of the results in the etiology of atherosclerosis. Am Heart J 1983;105:560-6 . 17. Sims FH. Discontinuities in the internal elastic lamina: a comparison of coronary and internal mammary arteries. Artery 1985;13:127-43. 18. Chamley-Campbel1 J, Campbel1 GR, Ross R. The smooth muscle cell in culture. Physiol Rev 1979;59:1-61. 19. Keyl MJ, Dowell RT, Yunice AA. Comparison of renal and cardiac lymph constituents. Lymphology 1980;13:158-60. 20. Loop FD, Lytle BW, Cosgrove OM, Golding LAR, Taylor PC, Stewart RW. Free (aorta-coronary) internal mammary artery graft: late results. J THORAC CARDIOVASC SURG 1986;92:827-31. 21. Daly RC, McCarthy PM, Orszulak TA, Schaff HV, Edwards WD. Histologic comparison of experimental coronary artery bypass grafts: similarity of in situ and free internal mammary artery grafts. J THORAC CARDIOVASC SURG 1988;96:19-29. 22. Tector AJ, Schmahl TM. Techniques for multiple internal mammary artery bypass grafts. Ann Thorac Surg 1984; 38:281-6. 23. Gold JP, Shemin RJ, DiSesa VJ, Cohn LH, Col1ins JJ. Multiple-vessel coronary revascularization with combined in situ and free sequential internal mammary arteries. J THORAC CARDIOVASC SURG 1985;90:301-3. 24. Kabbani SS, Hanna ES, Bashour TT, Crew JR, El1ertson DG. Sequential internal mammary-coronary artery bypass. J THORAC CARDIOVASC SURG 1983;86:697-702. 25. Rankin JS, Newman GE, Bashore TM, et al. Clinical and angiographic assessment of complex mammary artery bypass grafting. J THORAC CARDIOVASC SURG 1986;92:83246.