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Eur J Cardiothorac Surg 2006;30:333-340
© 2006 Elsevier Science NL
a Department of Cardiothoracic Surgery, German Heart Center Munich, Technical University of Munich, Lazarettstrasse 36, 80636 Munich, Germany
b Department of Anesthesiology, German Heart Center Munich, Technical University of Munich, Germany
Received 22 November 2005; received in revised form 23 April 2006; accepted 26 April 2006.
* Corresponding author. Tel.: +49 89 1218 4063; fax: +49 89 1218 4123. (Email: wildhirt{at}gmx.net).
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Abstract |
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 Top Abstract 1. Introduction2. Patients and methods3. Results4. DiscussionAppendix AReferences |
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Key Words: Radial arteries • Old age • Atherosclerosis • Intraoperative angiography
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1. Introduction |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionAppendix AReferences |
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In the last five years the radial artery has been used more often as a conduit for bypass surgery in particular in younger patients. The presence of risk factors for atherosclerosis, in particular diabetes has been evaluated in more detail prior to surgery. To date, there are still conflicting results for the use of radial arteries as bypass grafts. In recent studies it has been shown that patency rates for radial arteries are higher when compared with vein grafts at four- and five-year follow-ups [4,5]. In contrast, Buxton et al. [6] reported that in patients younger than 70 years of age, the radial artery grafts may not be superior to saphenous vein grafts. A recent randomized trial by Desai et al. [7] showed that the patency rates for radial arteries depend on the severity of the stenosis of the target vessel and should be preferentially used for coronary arteries with high-grade stenosis.
However, to date, it is not clear whether age per se may be an exclusion criterion for the radial artery used as a bypass graft. In addition, the severity of atherosclerotic lesions in radial arteries in patients beyond age 70 undergoing coronary artery bypass grafting (CABG) has not been evaluated.
In this study we determined radial artery graft function by intraoperative angiography and performed a detailed histopathologic and morphometric analyses of distal and proximal segments of radial arteries used as conduits for CABG in patients beyond age 70.
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2. Patients and methods |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionAppendix AReferences |
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2.1 Preoperative assessment of radial arteries
As a routine procedure, radial arteries of the non-dominant arm were assessed with the modified Allen's test and Doppler analysis to account for sufficient hand collateral circulation and palmar arch status.
All other exclusion criteria including Renauld's disease were also tested. Risk factors for atherosclerosis including diabetes, smoking, hypertension, hypercholesterolemia, positive family history, and age were not exclusion criteria per se.
2.2 Surgery for coronary revascularization with cardiopulmonary bypass
Intraoperative, the pedicled radial artery was harvested by two experienced surgeons exclusively. Radial artery harvesting was abandoned in case of small caliber and macroscopic evidence of significant calcification (Monckeberg's medial calcification). The RA was flushed with heparinized blood and soaked with papaverin until grafting. A 5 mm ring segment from the proximal and distal portion of the RA was stored in 3% paraformaldehyde for histologic and morphometric analysis.
Surgery was performed with cardiopulmonary bypass (CPB), mildhypothermia (32 °C), and blood cardioplegic arrest. The LIMA was grafted to the LAD in all patients. The second target vessel was always grafted with the RA, in most cases the marginal branches of the circumflex artery (Tables 1 and 2 ). The coronary artery was selected as the second target by size and quality of lesions (assessed by angiography and intraoperative inspection). All RA were grafted end-to-side using 7-0 Prolene running sutures.
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2.4 Intraoperative angiography of radial artery grafts
After blood flow measurement the femoral artery was punctured and a multi-purpose catheter was inserted in the ascending aorta. The radial artery graft was intubated and directly assessed by fluoroscopy. Images were stored for further analysis of stenosis and lesion formation. In one patient, fluoroscopy identified stenosis of the distal anastomosis and the graft was revised immediately.
2.5 Histopathology and morphometry of radial artery segments
The collected RA segments stored in 3% paraformaldehyde were further processed by de-parafinization. Sections were cut on a microtome (thickness 3 µm). Staining was performed with hematoxylin and eosin. Histopathology and morphometry were performed using the ImagePro Software to measure and calculate the following: the internal elastic lamina (IEL) circumference (IELC), intimal area, medial area, width of the intima, and width of the media. Diameter internal to the media (lumen + intima; DLI) and the IEL area (luminal area + intimal area; IEL area) were calculated (DLI = IELC/
and IEL area = IELC2/4, respectively).
Previous investigators have suggested that the intima-to-media ratio is the most sensitive method available for grading atherosclerosis [8–10]. In the present study, three methods were used to evaluate the degree of intimal thickening and atherosclerosis: (1) percentage of luminal narrowing (%LN), (2) intimal thickness index (ITI), and (3) the ratio of the width of the intima and width of the media at the maximum intimal thickness (IMR) (Fig. 1 ). The severity indices were calculated from the most severely diseased section of the specimens using the following formulas: %LN = 100 x intimal area/IEL area; ITI = intimal area/medial area; and IMR = width of intima at maximal intimal thickness/width of media at maximal intimal thickness.
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Eight clinical risk factors for intimal hyperplasia and atherosclerosis (age, sex, smoking, diabetes, hypertension, PVD, CVD, and hypercholesterolemia) of the RA were included in stepwise linear regression analyses as independent variables.
The percentage of luminal narrowing, ITI, and IMR were analyzed as dependent variables. For each regression model, we calculated the percentage of variation in the dependent variable explained by the model, a standard measure of the usefulness of the model. If this percentage is high, the model can be used to predict most of the variation in the dependent variable; if it is low, although the model may be useful, a large part of the variation in the dependent variable is explained by other factors.
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3. Results |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionAppendix AReferences |
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Measurement of graft flow showed excellent flow through all grafts with low resistance indices (flow: 76 ± 14 ml/min; PI: 2.2 ± 0.9).
3.2 Intraoperative angiographic graft assessment
Intraoperative angiography showed patent grafts in 26 patients (83.34%), some irregularities with no stenosis in 4 patients (12.9%), and surgical stenosis of the distal anastomosis in 1 patient (3.3%) that was revised immediately (Table 3
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4. Discussion |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionAppendix AReferences |
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4.1 Histopathologic findings
Intimal hyperplasia occurs as a consequence of tissue repair to maintain normal conditions of flow, wall tension, or both. Vessel segments with adaptive increases in intimal thickness are functionally impaired compared to thinner regions. Excessive lipoprotein in the plasma tends to accumulate preferentially in the hyperplastic intima, causing atherosclerosis [11].
However, the occurrence of intimal hyperplasia differs dramatically between vessel territories. In an early study by Kay et al., it was found that a >25% reduction in lumen diameter occurs in 4.2% of internal thoracic arteries in 215 examined vessels from routine postmortem examinations.
The incidence of medial calcification (Monckeberg calcinosis) in the RA was 7.8% (n = 3) in our study. Medial calcification of an artery, even when extensive, is not necessarily associated with extensive intimal changes, and the lumen of the artery may not be compromised. On the contrary, vessels with marked calcification often show less intimal involvement than is average for that age. However, in our study, the RAs with medial calcification did not have less intimal hyperplasia or atherosclerosis. Monckeberg's calcinosis is independent of and unrelated to the presence of atherosclerosis, but both are commonly found in patients older than 50 years and in patients with diabetes.
4.2 Morphometric findings
Several studies have investigated atherosclerotic changes in different vascular beds.
Kaufer et al. reported on the pathology of RAs and ITAs used as bypass grafts; they used the IMR to grade atherosclerotic lesions. The mean RA grade was significantly greater than the mean ITA grade; however, the classification of lesions was not clear (i.e., it was not clear whether the lesions represented intimal hyperplasia or true atherosclerosis), and the IMR may not have been a good indicator for comparative grading of vascular diseases. This is because a greater thickness of the media in the RA may lead to a misleadingly low IMR compared with an ITA with the same severity of intimal disease. The same authors found that the degree of disease in the RA was related to sex, age, diabetes, aorto-iliac atherosclerosis, and femoro-popliteal atherosclerosis. None of the risk factors correlated with the degree of ITA pathology [10].
Our findings indicate that those radial arteries found suitable for grafting by preoperative Doppler and modified Allen's test, may also be used in patients beyond age 70. This finding is of clinical importance for several reasons including the presence of preexisting vein graft disease and an increased number of first time and redo CABG in patients beyond 70 years.
This study adds new information to what has been described in the literature. A recent report by Ruengsakulrach et al. compared human radial arteries and internal thoracic arteries with regards to histopathology, morphometry, and risk factors for atherosclerosis. It was found that the RA is more likely to have atherosclerosis [12].
In a recent publication by Chowdhury et al. [13] it was demonstrated that the great majority of the harvested radial grafts have significant atherosclerotic disease. In contrast to our finding, in their studies, RA atherosclerosis was associated with classic risk factors including age, diabetes, and smoking. The predominant location of the diseased segments in their population was the distal part showing more severe intimal hyperplasia. The authors suggest that the distal segments of the radial grafts should be discarded whenever possible [13]. In line with this report others found an association of RA disease with established risk factors for atherosclerosis including age, diabetes, and smoking [12,14].
One difference to the results presented here may be the preoperative graft assessment performed by Doppler analysis and modified Allen's test. Those RA not found suitable by Doppler and Allen's test were not harvested and used as grafts. In addition, distal exploration of the RA was performed to assess the graft macroscopically. The presence of a small or calcified vessel abandoned the use of the RA as a graft. It may be that the amount and severity of atherosclerotic lesions may have been different if those patients would have been included. This further supports the notion that preoperative assessment of the RA by Doppler and Allen's test is of importance to evaluate RA graft suitability. Another application for the preoperative assessment of the radial artery suitability may be intravascular ultrasound as reported recently by Oshima et al. [15].
In spite of the prevalence of preexisting atherosclerotic disease in RA, one question may be of importance. Does the RA possess a better intrinsic tendency to stay patent over the long term compared with vein grafts and how to compare RA disease and vein graft disease?
Recent studies showed that the RA used as a second graft improved long-term outcomes when compared to vein grafts in CABG LITA-LAD patients [5,16]. In addition, it has been demonstrated that RA not only possess excellent long-term patency rates but also show preserved endothelial function and rarely develop flow-limiting, fibrous, intimal hyperplasia [4,17,18]. However, in some of these studies, RA with preexisting disease was excluded. In spite of the findings reported by Chowdhury et al. that the majority of RA have preexisting atherosclerosis, future studies are needed to evaluate its progression in RA used as conduits.
In conclusion, this study demonstrates that with careful preoperative assessment by Doppler and Allen's test as well as distal RA assessment intraoperative the RA can be used as graft for myocardial revascularization in older patients beyond age 70. Indeed, age should not be an exclusion criterion per se for the use of the RA as bypass graft in patients undergoing CABG for myocardial revascularization.
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Appendix A |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionAppendix AReferences |
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Dr P. Joshi (Penang, Malaysia): How do you administer nitric oxide intraoperatively into the artery?
Dr Wildhirt: We performed intraoperative angiography by direct administration of contrast media into the radial graft, and whenever we saw string signs we left the catheter in place and gave nitrovasodilators directly into the radial artery graft. In four patients we saw a very nice response in terms of resolving of those string signs, and we left the graft in place. As I showed in this one patient, there was no response and we revised the graft despite the fact that we had nice flow patterns.
Dr H.-J. Schaefers (Homburg/Saar, Germany): In other words, you gave nitroglycerin rather than nitric oxide?
Dr Wildhirt: Yes. Well, the bioactive drug is nitric oxide, but the chemical compound is nitrate/nitrite, absolutely.
Dr H.S. Bedi (Punjab, India): Very elegant study. It might have been more scientifically revealing if in the same patient you had compared the radial artery with another artery, for example, the internal mammary artery. And just to comment that, first, you did not mention the use or avoidance of the internal mammary artery; second, an unrelated comment that in all these high risk patients, they are all above 70 years old, you did on-pump surgery, which is a little surprising, because we would have done it off-pump in such a case. And the third question is in the patients with a string sign, was it the classical reason for the string sign, for example, a stenosis, which is not critical? Could that have been the cause for the string sign?
Dr Wildhirt: Dr Buxton's group from Australia published a lot on radial arteries and internal thoracic arteries as bypass grafts. The present study is an observational study to analyze the suitability of radial arteries as bypass grafts in older patients. It is difficult to compare both arteries, because they have, as you probably know, a very different atherosclerosis progression in the presence or absence of classical risk factors. The internal thoracic artery has essentially no atherosclerosis in those patients. Dr Buxton's group did compare both types of arteries and described the differences of histologic and morphometric changes, especially medial hyperplasia; it does not occur in internal thoracic arteries.
As we all know, the radial artery is very likely to develop atherosclerosis. In our opinion, the radial artery is useful in many patients beyond age 70. However, the patients should definitely be selected by Allen's test, and/or Doppler flow measurements prior to surgery and of course, in my opinion, in every patient the radial graft should be assessed by intraoperative angiography whenever possible.
Dr A. Scheule (Tuebingen, Germany): Do you have any explanation that the classic risk factors for arteriosclerosis do not apply to the radial artery? And the second question is, have you reviewed the Doppler studies of the patients with the string occlusions? It is surprising that you could not see signal reduction in the preoperative examination.
Dr Wildhirt: To answer the second question, the preoperative Doppler signal does not give you any idea about the responsiveness of the radial artery to vasospasm. We excluded surgical manipulation such as clipping of branches, which could have caused stenosis. All radial arteries were checked for that actually before the surgical procedure. Preoperative Doppler assessment does not give any information about the likelihood of spasm in those arteries, unfortunately. Therefore, we actually prefer to do angiography whenever we do radial arteries.
To answer your first question concerning risk factors, maybe it is just because of the small number of patients that we could not find any significant correlation to them. We did not perform multiple regression analysis because we only had 31 patients.
With an increasing number of patients there one could expect that this would be the case, especially with diabetes and maybe with the patients lipid status. However, most of the patients were on statins. We definitely should look into the effect of statins on atherosclerosis progression in the radial artery, and their potential to reverse atherosclerosic changes.
Dr H.-J. Schaefers (Homburg/Saar, Germany): Three short questions. First, did all radial arteries look pristine intraoperatively or were there some mild changes visible suggestive of maybe atherosclerosis? Second, is the pattern you showed typical for patients beyond the age of 70 or is this similar to patients, say, between the ages 50 and 70? Third, how much are the morphometric indices influenced by contraction? All of the slices I saw on your slides looked like contracted radial arteries, and if they were dilated in a better fashion, would that have an influence on your indices?
Dr Wildhirt: I will answer your last question first. We flushed the radial arteries but we did not dilate them intraoperatively before grafting.
Dr Schaefers: The important question. How did these arteries look when you harvested them? Did they all look absolutely clean or did they look like there were already some visible wall changes?
Dr Wildhirt: We started at the distal segment harvesting with a small cut. Whenever we saw multiple calcified changes, we excluded those arteries. We harvested all other arteries which looked distally normal. A great majority of vessels looked absolutely normal.
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Acknowledgments |
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Footnotes |
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Presented at the joint 19th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 13th Annual Meeting of the European Society of Thoracic Surgeons, Barcelona, Spain, September 25–28, 2005.
1 These authors contributed equally to the manuscript. 
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References |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionAppendix AReferences |
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  F. Onorati, F. Pezzo, M. C. Comi, B. Impiombato, A. Esposito, M. Polistina, and A. Renzulli Radial artery graft function is not affected by age. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1112 - 1120. [Abstract] [Full Text] [PDF]
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