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Ann Thorac Surg 1998;66:1972-1976
© 1998 The Society of Thoracic Surgeons

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Original Articles

Comparison of the morphologic and vascular reactivity of the proximal and distal radial artery

^a Department of Cardiothoracic Surgery, Imperial College of Science, Technology & Medicine, National Heart and Lung Institute, Harefield Hospital, Harefield, Middlesex, England, United Kingdom
^b Department of Cardiothoracic Surgery, Oxford Heart Centre, John Radcliffe Hospital, Oxford, England, United Kingdom

Accepted for publication June 2, 1998.

Address reprint requests to Dr Taggart, Oxford Heart Centre, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, England

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. Variations in the morphology and vascular reactivity of the proximal and distal radial artery might influence its performance as a bypass conduit.

Methods. The morphologic and functional characteristics of the proximal and distal RAs were compared with those of the left and right internal mammary arteries by using histologic and in vitro organ bath techniques.

Results. Proximal RA had a significantly greater medial cross-sectional area compared with that of the distal RA (2.48 ± 0.27 mm² compared with 1.86 ± 0.21 mm², p < 0.05), which were both significantly greater than the left internal mammary artery (0.54 ± 0.09 mm²) or the right internal mammary artery (0.67 ± 0.03 mm²). Proximal RA had a significantly greater response to 90 mmol/L potassium chloride than that of distal RA (88.4 ± 7.3 compared with 60.2 ± 10.3 mN, p < 0.05), and both contracted more than the left internal mammary artery (30.3 ± 2.9 mN) and the right internal mammary artery (32.6 ± 4.1 mN). There was no difference in the response to noradrenaline and adrenaline between proximal and distal RA, both of which contracted more than the left and right internal mammary arteries.

Conclusions. When choosing a segment of RA for use as a bypass conduit, regional variations in biologic properties should be considered.

	Introduction

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Although there was some disappointment with initial results [1–3], the radial artery (RA) is now increasingly being used as a conduit for coronary artery bypass grafting, as it combines good early results with satisfactory medium-term patency rates [4–6]. This improvement in results is believed to be from better harvesting techniques as well as the use of locally applied vasodilating agents during operations [7, 8].

The length of the RA harvested often exceeds that which is required for grafting, and because the RA is used as a free graft, there is a choice of which portion of the vessel is best to use. Variations in the biologic properties of the vessel wall can occur along the length of an artery, as well as between anatomically different blood vessels [9–13]. Such differences in the vascular smooth muscle and the endothelial cells lining the vessel wall have been implicated in influencing the short-term and long-term performance of different bypass grafts. Thus characterization of the biologic properties of proximal and distal RAs will provide important information for the use of this vessel as a bypass conduit.

In this study we assessed the morphologic and functional characteristics of the proximal and distal RA to see which segment has the better properties with regard to its use as a bypass graft, and we compared these characteristics with distal segments of the left (LIMA) and right internal mammary arteries (RIMA).

	Material and methods

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Portions of both proximal and distal RA, LIMA, and RIMA were removed from 9 male (aged 45–78 years; mean, 64 years) and 2 female (aged 69–73 years; mean, 67 years) patients who had coronary artery bypass grafting using arterial grafts. After median sternotomy, the LIMA and RIMA were harvested using low current electrocautery and titanium clips. Simultaneously, the RA was harvested from the left forearm using a combination of sharp dissection and titanium clips. During dissection, the RA was kept moist using normal saline irrigation. No systemic vasodilators were given, except for intravenous glyceryl trinitrate if the patient became excessively hypertensive. At the end of dissection, the RA was divided proximally and distally, and the internal mammary arteries (IMA) were divided at their distal attachments. No clamps were applied to vessels used in the study, and no hydrostatic or intraluminal dilation was used. Segments of the proximal and distal RA and distal LIMA and RIMA were removed and were immediately placed in a 199 tissue culture medium (Sigma, Dorset, UK). Excess connective tissue was removed under a dissecting microscope. Vessels were cut into segments 3 to 5 mm in length.

The vessel segments from each specimen were mounted on 2 L-shaped metal hooks in isolated organ baths, containing 5 mL of modified Tyrode’s solution of the following composition (mmol/L): NaCl 136.9, NaHCO₃ 11.9, KCl 2.7, NaH₂PO₄ 0.4, MgCl₂ 2.5, CaCl₂ 2.5, glucose 11.1, and disodium ethylenediaminetetraacetic acid 0.04, and continuously gassed with 95% O₂ and 5% CO₂. One hook was attached to a force-displacement transducer that was fixed to a Grass 7D polygraph (Grass Instruments, Quincy, MA), which monitored and recorded changes in vessel-wall tension. The second hook was fixed to a screw gauge, which was used to stretch the vessel segments.

Functional studies
Vessel normalization
After a stabilization period of 20 minutes, RA vessel segments were stretched initially by 50 mN, and IMA segments stretched by 40 mN. Both vessel types were then progressively stretched in 20-mN increments. Between each stretch, segments were challenged with 90 mmol/L potassium chloride solution (KCl). The response to each addition of KCl was allowed to reach a plateau before being washed out. The tension in each segment was permitted to return to a stable baseline before the next stretch. When two KCl responses were within 10% of each other the vessel segments were judged to be stretched to their optimum diameter for smooth muscle cell contractility. The use of KCl was intended only as a tool to measure smooth muscle cell contractility independent of receptor stimulation.

Experimental protocol
After an additional stabilization period of 30 minutes, each vessel segment was challenged with either noradrenaline (10^-10 to 10^-4 mol/L) or adrenaline (10^-10 to 10^-4 mol/L) (Sigma Poole, Dorset, UK). These drugs were added to the bath in a cumulative fashion in log₁₀ units. The response of each concentration was allowed to reach a plateau before addition of the next concentration of each drug.

Histologic studies
On completion of each concentration-response curve, the vessel segments were removed from the organ baths, mounted on filter paper, and flash frozen in liquid nitrogen. These segments were subsequently cut into 6-µmol/L-thick sections on a cryostat and stained with Meyer’s elastin stain. Sections were viewed under a light microscope and analyzed with a image analyzer to measure (in millimeters) the vessel diameter (VD) and the internal (lumen) diameter (ID) (also in millimeters). From these measurements the medial cross-sectional area (MCSA) (mm²) was calculated according to the following equation: MCSA = (VD/2)² - (ID/2)².

Data analysis
Contractile responses were expressed as the mean ± standard error of the mean for the absolute millinewton increases in tension induced by each concentration of drug. Statistical comparisons were made using the Mann-Whitney U test. Results were considered significant with p values <0.05.

	Results

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Functional studies
The contractility, in response to 90-mmol/L KCl, of rings of proximal and distal RA was significantly greater than that of the LIMA and RIMA (p < 0.05). Proximal RA segments also generated significantly more tension when challenged with KCl than distal segments of the RA (p < 0.05). In contrast, the LIMA and RIMA had statistically similar responses to KCl (Fig 1).

View larger version (18K): [in this window] [in a new window]   Fig 1. Contractile effect of 90-mmol/L KCl on segments of proximal radial artery (n = 7), distal radial artery (n = 7), left (n = 8) and right internal mammary artery (n = 4). **p < 0.001 for proximal radial artery compared with all other groups); *p < 0.05 for distal radial artery compared with all other groups. **p < 0.05 for proximal radial artery compared with left and right internal mammary artery.

View larger version (18K): [in this window] [in a new window]   Fig 2. Contractile response to increasing concentrations of noradrenaline in the radial artery ( = proximal segments, n = 7; • = distal segments, n = 7) and the internal mammary artery (* = left, n = 8; = right, n = 4). *p < 0.05 for proximal radial artery compared with the left internal mammary artery.

View larger version (18K): [in this window] [in a new window]   Fig 3. Contractile response to increasing concentrations of adrenaline in the radial artery ( = proximal segments, n = 7; • = distal segments, n = 7) and the internal mammary artery (* = left, n = 8; = right, n = 4). *p < 0.05 for proximal radial artery compared with the left and right internal mammary artery.

View larger version (129K): [in this window] [in a new window]   Fig 4. Representive segments of (A) proximal radial artery, (B) distal radial artery, (C) left internal mammary artery, and (D) right internal mammary artery stained with elastic van Gieson.

	Comment

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The present study shows that isolated rings of RA exhibit an increased force of contraction in response to commonly used vasopressor. This property of the RA is due to a greater amount of medial smooth muscle in the RA compared with the IMA and may explain its propensity to spasm in clinical practice. It has been shown previously that the RA contains more muscle in its wall compared with other arterial conduits and that its contractility is greater than that of the IMA [17, 18]. In addition, our data also suggest that there is more muscle in the proximal RA vessel wall compared with the distal RA, which is reflected by the greater contractility of the proximal segments. However, we were unable to demonstrate a difference in the internal diameters between the proximal and distal RA segments. This finding most likely results from the vessels not being fixed under pressure and removed from the organ baths in a contracted state (ie, after administration of the highest concentration of either adrenaline or noradrenaline), both of which would underestimate their size and normalize differences between them.

The RA supplies a somatic bed, and in the arm gives off branches to muscle. The size of the vessel would therefore be expected to change along its length as it carries progressively less blood flow. As the nature of its distribution does not change, it is surprising that the vasoreactivity, as a reflection of the degree of muscularity of the wall, is different. We found no significant difference in the responses to agents that are both endogenous vasoactive mediators and commonly used vasopressors. Because the contractility of the vessel wall varies along its length (as judged by the response to KCl), the lack of a similar pattern for the action of adrenaline and noradrenaline suggests that the profile of adrenoceptors, at which adrenaline and noradrenaline act, might vary along the vessel. This variation in receptor profile might compensate for the variations in medial smooth muscle content. There was a notable variation in the magnitude of response of the distal segments of RA to noradrenaline and adrenaline, which prevented there being a statistical difference between the distal RA and the LIMA or RIMA in response to these two agents. This variability might be linked to the vulnerability of this area of the RA to spasm in response to catecholamines. Further functional and receptor-binding studies are required to map the distribution and variability of adrenoceptors in this artery.

Focal vascular smooth muscle vasoconstriction or vasospasm can occur in response to a wide range of physiologic and pharmacologic stimuli. The factors that dictate the degree of spasm capable by an artery are governed by the contractility of the vessel wall. This contractility is regulated by the general reactivity of the vascular smooth muscle, the profile of receptor subtypes, and the integrity of the endothelium. We and others have shown that the radial artery shows a capacity for vascular contraction several-fold greater than the IMA [17] which occurs both with and without the presence of a functional endothelium in vitro [18]. In the present study we did not assess the function of the endothelium in each segment used in the study. Although such measurements might have indicated the possibility of enhanced sensitivity to vasoconstrictors, the histologic examination of the arteries showed the endothelial lining generally to be intact and the segments free of major atherosclerotic changes. We also have found that the response to acetylcholine is comparable to that seen in the IMA (unpublished data), an observation supported by a recent study [19].

The greater contractility of proximal segments of RA suggests that in this region contraction of the vessel wall will have a greater impact on vessel size than that seen in the distal segment. However, clinical practice has shown that it is the distal end of this vessel that is prone to spasm [15], a phenomenon that is also observed with the IMA and gastroepiploic artery [20, 21]. Thus, although the proximal portion of the RA contains more smooth muscle, the influence of the smaller diameter at the distal end might allow a pharmacologic stimulus to have a greater effect on vessel diameter, and therefore flow, than in the distal region of the vessel. There is evidence for cross-talk between signaling pathways that mediate vascular contraction and those that are involved with smooth muscle cell growth [22], indicating that contraction of the vessel wall might be an important step in the activation of growth-promoting pathways. Additional studies are required to examine the relationship between agents that possess both vasoactive and growth-promoting properties and to assess their potential regional effects in the initiation of intimal proliferation in the graft.

In conclusion, there appears to be a difference in functional characteristics between the proximal and distal RA in that the force of maximal contraction of the proximal RA is greater than that of the distal RA. This difference might be because they have different morphologic characteristics, as the proximal RA has a greater muscle content than the distal RA. Understanding the mechanisms that regulate vessel tone in the RA and the response of the vessel wall to endogenous and exogenous pharmacologic stimulation are important in optimizing its use as a bypass conduit.

	References

Top Abstract Introduction Material and methods Results Comment 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): Adrian J. Marchbank Magdi H. Yacoub David P. Taggart Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chester, A. H. Articles by Taggart, D. P. Search for Related Content PubMed PubMed Citation Articles by Chester, A. H. Articles by Taggart, D. P. Related Collections Related Article