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J Thorac Cardiovasc Surg 2000;120:298-301
© 2000 The American Association for Thoracic Surgery

Surgery for acquired cardiovascular disease

Midterm endothelial function and remodeling of radial artery grafts anastomosed to the aorta

From the Departments of Cardiac Surgery^a and Cardiology,^b Catholic University, Rome, Italy.

Address for reprints: Mario Gaudino, MD, Divisione di Cardiochirurgia, Policlinico Universitario A. Gemelli, Largo A. Gemelli 8, 00168 Rome, Italy (E-mail: mgaudino{at}tiscalinet.it ).

	Abstract

Top Abstract Introduction Patients and methods Results Discussion References

 
Background: The purpose of this study was to elucidate the midterm endothelium-dependent vasodilatory capacity of radial artery grafts anastomosed to the aorta, as well as their morphometric evolution with the time.
Methods: Five years after surgery we evaluated the response of aorta-anastomosed radial artery grafts to the endovascular infusion of acetylcholine in 11 of the first 61 patients operated on at our institution, and we compared it to the response with that of internal thoracic artery grafts. Moreover, the first 20 patients who had a perfect radial artery graft on angiography at 1 year were restudied at 5 years and subjected to a comparative analysis of the diameters of the radial artery graft and the grafted coronary arteries.
Results: At midterm angiography, dilation of the 2 types of grafts was similar in response to acetylcholine administration (radial artery, from 2.61 ± 0.39 to 2.90 ± 0.34 mm; internal thoracic artery, from 2.68 ± 0.21 to 2.93 ± 0.27 mm; P = .01 for both). The diameters of aorta-anastomosed radial artery grafts and grafted coronary arteries increased between both 1 and 5 years according to angiographic studies (radial artery grafts, from 2.08 ± 0.45 to 2.54 ± 0.53 mm; grafted coronary arteries, from 1.92 ± 0.47 to 2.18 ± 0.41 mm; P < .001 for both), but the increase was greater for the radial artery grafts (P < .001).
Conclusions: Aorta-anastomosed radial artery grafts maintain an appreciable capacity for endothelium-dependent vasodilatation 5 years after implantation and undergo a progressive increase in luminal diameter with time. These observations contradict the presumed tendency for progressive fibrous intimal hyperplasia to develop in radial artery grafts.

	Introduction

Top Abstract Introduction Patients and methods Results Discussion References

 
The radial artery (RA) is gaining wide acceptance as a complementary arterial conduit for myocardial revascularization. ¹ Although the early angiographic patency of RA grafts has been reported to be satisfactory, ^2-6 concerns have been expressed on the routine use of this artery, mainly on the basis of its presumed hyperreactivity and the propensity for fibrous intimal hyperplasia to develop when the RA is anastomosed to the ascending aorta. ^7-9

This study was conceived to elucidate the midterm endothelium-dependent vasodilatory capacity of RA grafts anastomosed to the ascending aorta (AARA), as well as their morphometric evolution with the time.

	Patients and methods

Top Abstract Introduction Patients and methods Results Discussion References

 
After approval by the Ethic Committee of the Catholic University of Rome, a study on the use of the RA as a coronary artery bypass conduit was prospectively started in January 1993. The 3 main objectives of the study were to establish (1) the midterm and long-term clinical and angiographic results of RA grafts, (2) the long-term effect of RA removal on the forearm blood supply, and (3) the midterm endothelial function of RA grafts and their morphometric evolution with the time.

The first 2 issues have already been addressed in other publications. ^10-13 The present report was conceived to clarify the third point (RA midterm endothelial function and morphometric evolution), which assumes particular relevance in view of the concern expressed by some authors on the possible accelerated development of intimal hyperplasia when RA grafts are directly anastomosed to the ascending aorta. ^2-4

Patient population
A total of 28 patients were chosen from the first 61 patients in whom the RA was directly anastomosed to the ascending aorta (AARA grafts)—the first 20 in whom the AARA was perfectly patent angiographically at 1 year and in whom both the AARA graft and the corresponding grafted coronary arteries were measured at 1 and 5 years’ follow-up and 11 patients with a perfect AARA graft at early angiography who gave their approval for the performance of an acetylcholine challenge during the 5-year follow-up. Three of the patients subjected to serial measurement of the AARA and the grafted coronary arteries also agreed to have the acetylcholine challenge and thus were included in both groups.

The mean preoperative characteristics of the patients are shown in Table I. Among the patients subjected to serial measurement of the AARA and the grafted coronary arteries, the RA was anastomosed to an obtuse marginal branch in 15 patients, a posterior descending branch in 3, and a first diagonal branch in 2 patients. The RA was anastomosed to an obtuse marginal branch in all patients subjected to the acetylcholine challenge, except for the 2 patients in whom it was used to revascularize a posterior descending branch.

View larger version (31K): [in this window] [in a new window]   Fig. 1. Site of angiographic measurements of radial artery grafts (RA, 1), grafted coronary arteries (GCA, 2), and internal thoracic artery grafts (ITA, 3).

Angiographic images were measured with the use of quantitative computerized angiography (Medis, Amsterdam, The Netherlands), as this system has a lower detection limit of 0.6 mm. Structures with a lesser value were considered to be 0.6 mm in diameter. All measurements were carried out separately by 2 different observers blinded to each other’s assessments. Major discordances were resolved after common re-evaluation.

Statistical analysis
Data are expressed as mean ± 1 SD. Changes in the diameter of the AARAs and ITAs were expressed as absolute and percentage differences from baseline values. AARA and ITA diameters at baseline and in response to acetylcholine infusion, as well as AARA and grafted coronary artery diameters at 1 and 5 years of follow-up, were compared by 2-way analysis of variance for repeated measures, for F values less than 0.05. Pairwise comparisons were then performed by means of the Newman-Keuls t test for paired data. Diameters of AARA and ITA grafts and grafted coronary arteries were compared by means of the Student t test for unpaired data.

	Results

Top Abstract Introduction Patients and methods Results Discussion References

 
The 28 patients included in this report are part of the first 61 patients with AARA grafts restudied for midterm angiographic follow-up at our institution; their detailed angiographic results have already been published. ¹² On angiography, all had a perfectly patent AARA graft at 1 year. When restudied at 5 years, all 28 patients were confirmed to have a perfect AARA graft (perfect patency rate: 100%).

Acetylcholine challenge
Both AARA and ITA grafts increased significantly in diameter after acetylcholine infusion (respectively, from 2.61 ± 0.39 to 2.90 ± 0.34 mm and from 2.68 ± 0.21 to 2.93 ± 0.27 mm; P = .01 for both). The capacity of endothelium-dependent vasodilatation was not appreciably different between the 2 conduits (P = .60).

Serial measurement of RA diameter
Diameters of AARA grafts and grafted coronary arteries at 1 year were of comparable size (2.08 ± 0.45 mm vs 1.92 ± 0.47 mm; P = .25). AARA graft diameters increased by 22% at 5 years’ follow-up (2.08 ± 0.45 mm vs 2.54 ± 0.53 mm; P < .001), whereas the grafted coronary arteries increased in diameter by 13.3% (1.92 ± 0.47 mm vs 2.18 ± 0.41 mm; P < .001). Overall, the absolute diameter gain was much greater in AARA grafts than in the grafted coronary arteries (0.46 ± 0.38 mm vs 0.27 ± 0.36 mm; P < .001).

	Discussion

Top Abstract Introduction Patients and methods Results Discussion References

 
The easy accessibility and optimal caliber and length of the RA, coupled with an increasing interest in arterial grafts, had led to the growing use of this conduit in coronary surgery. Several groups have reported favorable angiographic and clinical results. ^2-6 However, the RA is a purely muscular artery with a strong vasoreactive response to a variety of external stimuli, and some authors have expressed concern about the potential clinical consequences of its spastic tendency. ^7,8

Our group has shown that the hyperspastic characteristic of the RA tends to decline with time ¹²; in fact, the early vasoconstrictive reaction of this conduit after endovascular infusion of serotonin is significantly reduced at midterm follow-up and does not differ from that of ITA grafts, despite the known histologic and biologic differences between these 2 arteries. ^7,14 These findings are in accordance with the observation that continuation of Ca⁺⁺ channel blocker therapy after the first postoperative year did not influence the patients’ clinical status and RA angiographic results. ¹²

Another issue of major concern with regard to RA grafts is their presumed propensity for the development of flow-limiting degrees of intimal hyperplasia, especially when anastomosed directly to the ascending aorta. It has been speculated that the histologic and structural characteristics of the RA can render this conduit particularly prone to vessel wall ischemia and consequent intimal proliferation, especially when exposed to the hemodynamic stress due to the sharp increase in P/T present in the initial part of the ascending aorta. ^4,7,9 For this reason some authors have advocated performing the proximal anastomosis of RA grafts to a vascular region with a lower P/T, such as an ITA graft. ^2,4

This study is in contrast to what is thought to be a tendency of AARA grafts to be affected by intimal hyperplasia. In this study in patients who underwent comparative measurements of the AARA at early and midterm follow-up, the diameter of the artery significantly increased over time; five years after surgery, AARA grafts maintained an appreciable endothelium-dependent vasodilating capacity not inferior to that of the gold standard ITA, which strongly argues against the presence of a hyperplastic regenerated endothelium.

Although in the absence of histologic data or endovascular echographic imaging of the graft wall the development of intimal disease cannot be definitely excluded, it seems that a favorable morphofunctional remodeling of the RA grafts with a progressive reduction of the hyperspastic characteristic and an increase in luminal diameter occur with time, even when the conduit is directly anastomosed to the ascending aorta. On the other hand, when exposed to a major increase in flow (such as after creation of an arteriovenous fistula in patients with dialysis-dependent renal failure), in situ RAs undergo progressive remodeling, characterized by a striking increase in internal diameter without vessel wall hypertrophy and with unchanged intimal and medial thickening. This response further demonstrates the low propensity of this artery to the development of flow-induced intimal hyperplasia. ¹⁵

In addition, our study shows that in the years after the operation the diameter of both the AARAs and the target coronary arteries increased significantly. Although the exact physiologic basis of this phenomenon remains unclear, the parallel increase of the diameters of the 2 vessels suggests that hemorheologic conditions could play a major role in these changes. In fact, after successful surgical grafting there is an obvious increase in flow velocity and shear stress in both the conduit and the grafted artery, and shear stress is known to be a powerful stimulus for the production of nitric oxide, whose dilating effect on the vessel wall is widely known. ¹⁶ Thus the superior dilatation of the AARA graft could probably be explained on the basis of its demonstrated high sensitivity to nitric oxide ¹⁷ and of the superior degree of freedom from atherosclerotic involvement and consequent superior production of endogenous vasodilators when compared with grafted coronary arteries.

In conclusion, follow-up several years after surgery shows that the RA undergoes favorable morphologic and functional remodeling with a progressive increase in diameter and reduction of the early hyperspastic characteristic while maintaining an appreciable capacity of endothelium-dependent vasodilatation. These observations and the good angiographic results further support the use of the RA as a complementary arterial conduit for surgical myocardial revascularization.

	References

Top Abstract Introduction Patients and methods Results Discussion References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Mario Gaudino Franco Glieca Gianfederico Possati Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gaudino, M. Articles by Possati, G. Search for Related Content PubMed PubMed Citation Articles by Gaudino, M. Articles by Possati, G.