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Histological and Morphometric Properties of Skeletonized Gastroepiploic Artery and Risk Factors for Intimal Hyperplasia

Phung, Doan Van MD; Kinoshita, Takeshi PhD; MD; Asai, Tohru MD, PhD; Suzuki, Tomoaki MD, PhD

Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery: May/June 2012 - Volume 7 - Issue 3 - p 191–194
doi: 10.1097/IMI.0b013e318264f4cb
Original Articles

Objective: The aim of the present study was to examine the histological and morphometric properties of skeletonized gastroepiploic artery (GEA) and the risk factors for intimal hyperplasia.

Methods: We obtained the redundant distal segments of skeletonized GEAs from 33 patients undergoing coronary bypass surgery and microscopically examined the transverse sections just distal to the most distal anastomoses. Intimal hyperplasia was evaluated on the basis of intima-to-media ratio and percentage of luminal narrowing. Risk factors were examined using multivariate linear regression analysis.

Results: The median (range) of lumen diameter at the most distal anastomosis was 3.8 (2.4–6.4) mm; width of intima, 82 (8–418) μm; width of media, 167 (88–351) μm; wall thickness, 250 (118–554) μm; intima-to-media ratio, 0.59 (0.04–3.88), and percentage of luminal narrowing, 12.3 (1.5–28.9). The number of elastic lamina in the media was 4.2 ± 1.8. Atherosclerosis was found in six patients, and medial calcification, in three patients. The median (range) of graft flow and pulsatile index measured by intraoperative transit-time flow meter was 65 (11–141) mL/min and 3.1 (1.4–5.9), respectively. All GEA grafts were patent at the coronary computed tomography angiography before discharge. Estimated glomerular filtration rate was independently associated with intima-to-media ratio (β coefficient = −0.016, P < 0.01) and percentage of luminal narrowing (β coefficient = −0.012, P < 0.01).

Conclusions: Skeletonized GEA had sufficient lumen diameter with excellent graft flow and early patency even when used as a sequential graft. Estimated glomerular filtration rate correlates significantly with intimal hyperplasia.

From the Division of Cardiovascular Surgery, Shiga University of Medical Science, Otsu, Japan.

Accepted for publication May 26, 2012.

Drs Phung and Kinoshita are the co–first authors.

Disclosure: The authors declare no conflict of interest.

Address correspondence and reprint requests to Takeshi Kinoshita, MD, PhD, Shiga University of Medical Science, Setatsukinowa, Otsu 520-2192, Japan. E-mail:

The right gastroepiploic artery (GEA) has been used as an alternative conduit for coronary bypass surgery.1–3 However, its small caliber size and vasospasm are major concerns in using the GEA. The skeletonization technique was initially applied as a method to harvest the internal thoracic artery (ITA) and has been reported to increase the caliber size, conduit length, and flow capacity.4–6 It can therefore be expected that skeletonized GEA should realize the same benefit as skeletonized ITA and subsequently provide a better patency rate than pedicled GEA. Indeed, one study revealed a higher 4-year cumulative patency with skeletonized GEA than in a previous study by the same author with pedicled GEA.2,7 However, there is little detailed quantitative evaluation of skeletonized GEA. The aim of the present study was to examine its histological and morphometric properties.

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Patients had previously granted permission for use of their medical records for research purposes. The study was approved by the institutional review board. Discarded human GEA tissues were obtained from 33 patients who underwent coronary bypass surgery. The baseline characteristics are summarized in Table 1. Glomerular filtration rate (mL/min/1.73 m2) was calculated from the Modification of Diet in Renal Disease equation.8

Our indication for the use of the GEA was patients who had more than 90% stenosis in the right coronary territory or the posterolateral branch of the circumflex branch. The GEAs were dissected proximal to the pylorus and distal to the midpoint of the greater curvature of the stomach. Full skeletonization of the whole length of the GEA was performed with an ultrasonic scalpel.9,10 After systemic heparinization, the distal end of the graft was divided, and 0.02% milrinone was instilled into the graft, which was then wrapped with a 0.2% papaverine-soaked sponge. The required length of GEA was adjusted by the target vessels, and the redundant distal portion was trimmed and sent to the laboratory. The off-pump technique was used in all patients without emergent conversion to cardiopulmonary bypass. The details of the surgical technique have been described previously.11 No GEA was discarded on the basis of the gross examination carried out after opening of the peritoneal cavity or after graft harvest was completed.

Graft flow tracing was recorded intraoperatively using a transit-time flow meter (VeriQc; Medi-Stim, Oslo, Norway). A 3- or 4-mm probe was placed around the distal portion of the graft when the hemodynamic status became stable with a mean blood pressure between 70 and 90 mm Hg before chest closure. Coronary computed tomography (CT) angiograms were performed using a 320-channel multidetector CT (Aquilion ONE; Toshiba Medical Systems Corporation, Tokyo, Japan). Patients were routinely scheduled for early follow-up coronary CT angiography 1 week postoperatively before discharge. In patients with renal dysfunction, defined as a estimated glomerular filtration rate less than 60 mL/min/1.73 m2, coronary CT angiograms were performed after appropriate hydration in consenting patients only. The graft patency status was classified into one of three descriptive imaging categories: patent, faint (visualization but with significant stenosis, >50% of luminal narrowing, or string sign), or nonvisualized. A nonvisualized graft was regarded as occluded. Sequential grafts were considered as separate grafts.

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Histopathological Analysis

The obtained GEA tissues were fixed in 5.25% formaldehyde solution. Subsequently, the specimens were embedded in paraffin wax and transverse sections were obtained. Care was taken to ensure that the sections were not oblique and not adjacent to branching points. After dewaxing, they were stained with hematoxylin-eosin and Verhoeff Van Gieson stain. In morphometric analysis, the following variables were measured using a color image system (Image Pro Plus version 6.2, Medial Cybernetics, Bethesda, MD USA): lumen diameter, maximum width of intima, width of media at maximal intimal thickness, and wall thickness. Intimal thickening was evaluated using two methods: (1) ratio of maximal width of intima to width of media at maximal intimal thickness and (2) percentage of luminal narrowing (100 × intimal area/internal elastic lamina area). The number of elastic lamellae in the media was counted by dividing the section into eight equal sectors of 45 degrees. The number of well-stained, uninterrupted medial elastic lamellae present in each region was counted and averaged for each cross-section. The number of discontinuities in the elastic lamellae was recorded. An atherosclerosis lesion was defined by the presence of intimal lipid lying free as cholesterol clefts or in aggregates of foamy macrophage. Medial calcification was recorded in the case of calcium crystal being present in the media tunica (Fig. 1).

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Statistical Analysis

The association of preoperative risk factors with intimal hyperplasia was assessed by stepwise linear regression analysis. The following nine clinical risk factors were included as independent variables: age, sex, body mass index, smoking, diabetes, estimated glomerular filtration rate, hypertension, peripheral arterial disease, and hyperlipidemia. The intima-to-media ratio and percentage of luminal narrowing were analyzed as dependent variables after logarithmic transformation because of the skewed distribution. To examine the multicollinearity of the model, the variance inflation factor for each variable in the model was calculated to confirm that none exceeded 2 (highest, 1.242), which indicates that multicollinearity was not a significant issue. The correlation of two continuous variables was checked using the Spearman rank correlation test. All statistical testing was two sided. Results were considered statistically significant at a level of P < 0.05. All analyses were performed with the SPSS statistical package version 20.0 (SPSS Inc, Chicago, IL, USA).

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The median of lumen diameter at the distal anastomosis was 3.8 mm (range, 2.4–6.4 mm) in the GEAs (Table 2). The GEAs were used as sequential grafts in 16 patients (48%, 16/33). The median of graft flow and pulsatile index measured by intraoperative transit-time flow meter was 65 mL/min (range, 11–141 mL/min) and 3.1 (range, 1.4–5.9), respectively, in the GEAs. Table 3 summarizes lumen diameter at the distal anastomosis and transit-time flow measurement according to the alignment of the GEAs. Graft flow tended to be greater in sequential grafting. All GEA grafts were patent at the coronary CT angiography before discharge. The number of elastic laminae in the media was 4.2 ± 1.8 (range, 3–10) in the GEAs. The number of discontinuities in the internal elastic lamina was 41 ± 23 (range, 12–125) in the GEAs. Atherosclerosis was found in six of the GEA segments. All the atherosclerotic lesions were fibroatheromas. Pure lipid plaques were not seen. Medial calcification was found in three of the GEA segments. The results of stepwise linear regression analysis of the risk factors for intimal hyperplasia in GEAs are shown in Table 4. Estimated glomerular filtration rate was independently associated with intima-to-media ratio and percentage of luminal narrowing. Figure 2 illustrates the relation between estimated glomerular filtration rate and intima-to-media ratio and percentage of luminal narrowing. When estimated glomerular filtration rate decreased, the severity of intimal hyperplasia increased.

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The present study has two key findings. The first is that the skeletonized GEA had a sufficient lumen diameter at the distal anastomosis and provided an excellent graft flow and early graft patency. This contrasts with other studies of GEA harvested using the conventional pedicled technique.1,12 Pym and colleagues1 performed coronary artery bypass graft surgery on 126 patients using pedicled GEAs and reported that the lumen diameter at the site of the distal anastomosis ranged from 1.25 to 2.5 mm and was usually just under 1.5 mm. Van Son and coworkers12 examined the pedicled GEAs obtained at autopsy from 28 patients and showed that the luminal diameter of the GEAs gradually decreases along its course: 2.7 ± 0.3 mm at the origin, 2.2 ± 0.4 mm at 10 cm, and 1.8 ± 0.5 mm at 15 cm. The difference suggests that skeletonization plays an important role in facilitating the use of the GEA as a bypass conduit. The vascular tone of the GEA can vary during an operation more easily than that of the ITA. This may be attributable to the fact that the GEA contains less elastic fiber in the media than the ITA does. In our opinion, it is most important that each GEA conduit be prepared at its maximal dilatation before anastomosis. Skeletonization may increase the length of the GEA, facilitate visual inspection, and subsequently enable the small and highly vasospastic part of the GEA to be trimmed off so that more proximal portion with large lumen diameter can be used even if it is for a sequential graft. In other words, because the first visual inspection and manual palpitation of the GEA does not predict the potential size of the artery, care should be taken not to underestimate the size of the GEA at the beginning.

The second is that estimated glomerular filtration rate correlated with severity of intimal hyperplasia in the GEA. In patients with renal disease, factors such as hypertension, lipid abnormality, anemia, fluid overload, platelet dysfunction, or parathyroid dysfunction with hypercalcemia hasten the process of atherosclerosis.13 A unique feature of the vessel in patients with renal disease is intimal hyperplasia with medial calcification in peripheral and coronary arteries.14,15 Our findings indicate that decreased estimated glomerular filtration rate accelerates the development and progression of atherosclerosis in the GEAs and contributes to subsequent graft insufficiency and poor outcome.

There are some reports of microscopic examination of the GEA. Malhotra et al16 investigated specimens of pedicled GEA taken from patients undergoing coronary bypass grafting and demonstrated that the mean internal radius (width of intima plus half of lumen diameter) was 28 μm (range, 5–47 μm). This finding is quite different from our result. Van Son et al12 demonstrated that the GEA generally showed mild intimal hyperplasia at its origin (width of intima, 50 ± 49 μm) with a gradual decrease in intimal hyperplasia along its course (width of distal intima, 10 ± 17 μm), that the width of the media was 380 ± 116 μm at the origin and 115 ± 70 μm at the distal segment, and that the number of discontinuities in the internal elastic lamina was constant (86 ± 30 at the origin, 93 ± 29 at 5 cm, and 58 ± 17 at distal segment). Our results are consistent with these findings.

This study has several potential limitations. First, it enrolled only a small number of patients and had no comparison group. Second, the vessels analyzed in the study were discarded distal graft segments. Finally, the lack of available coronary angiography did not allow us to evaluate the association between our microscopic findings and long-term graft patency.

In conclusion, skeletonized GEA had sufficient lumen diameter with excellent graft flow and early patency even when used as a sequential graft. Estimated glomerular filtration rate correlates significantly with intimal hyperplasia in the right GEA.

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This is an interesting article from Dr Phung and his colleagues from Shiga University in Japan. They obtained the distal segments of skeletonized gastroepiploic arteries from 33 patients undergoing coronary artery bypass graft surgery. These vessels were examined histologically and found to have adequate luminal diameter. Atherosclerosis was identified in 6 of the patients. The estimated glomerular filtration rate correlated significantly with the degree of intimal hyperplasia. This study suggests that these grafts should be used with caution in patients with renal insufficiency or evidence of accelerated peripheral atherosclerosis. The drawback of this study was the lack of follow-up angiography, which did not allow the investigators to examine the association between their microscopic findings and graft patency.


Coronary bypass surgery; Gastroepiploic artery; Histology

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