Steroids and

Immunosuppression

Effect on Anastomotic Intimal Hyperplasia in Femoral Arterial Dacron Bypass Grafts Lawrence M. Hoepp, MD; Ahmad Elbadawi, MD; Michael Cohn, MD; Robert Dachelet, MD; Charles Peterson, MD; James A. DeWeese, MD

\s=b\ The effects of steroids and immunosuppression on 6-cm long bilateral femoral arterial Dacron bypass grafts were studied in 30 adult mongrel dogs. The dogs were serially placed into one of the following three groups: control, steroid, and immunosuppression. The control and steroid groups each had a 70% graft patency rate, whereas the immunosuppression group had a 100% eight-week graft patency rate. The results in the steroid group were not statistically different from the control group, whereas the results in the immunosuppression group were statistically different from the control. The decrease in internal diameter was secondary to a localized accumulation of tissue at the anastomotic site, which histologically appeared to be a hyperplastic intima morphologically different in each group. There is a substantial decrease in intimal hyperplasia at anastomotic sites and a higher graft patency rate in dogs treated with low-dose azathioprine as compared with control or steroid\x=req-\

treated animals. The mechanism seems to be a slower and more orderly intimalization rather than suppression of any specific intimal cellular elements.

(Arch Surg 114:273-276, 1979) failure of arterial bypass grafts in the early postop¬ erative period is commonly ascribed to technical factors. The cause of late failures of arterial bypass grafts is more complex and not as clearly understood. A current theory holds that unless there is full endothelialization of the graft, the thrombogenic material that coats the lumen leads to sufficient narrowing that any decrease in flow can lead to complete thrombosis.1 Studies in our laboratory, on the other hand, implicate a localized intimai hyperplasia and stenosis at the anastomosis as the reason for thrombo¬ sis.2 The reason for the development of the excessive intimal¬ ization is unknown. There is a possibility that this build-up is a low-grade inflammatory process, in which case steroids might affect the development of the lesions. Recent studies

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publication June 2, 1978. Department of Surgery, University of Rochester (NY) Medical

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in canine homograft carotid arteries show a more ordered intimalization with the use of low-dose azathioprine,1 suggesting that this drug might alter the characteristics of the hyperplasia. In an effort to further delineate the cause of late arterial bypass graft failures and attempt to prolong graft paten¬ cy, the following study using steroids and immunosuppres¬ sion was undertaken in a canine standard femoral-poplit¬ eal Dacron arterial bypass graft model.' MATERIALS AND METHODS

Thirty-one adult mongrel dogs weighing .15 to 27 kg were anesthetized with intravenous pentobarbital sodium. Under sterile conditions, a bilateral longitudinal incision was made medial to the sartorius muscle in the thigh and the femoral artery was exposed from the inguinal ligament to slightly beyond its first bifurcation. Heparin sodium, 1,500 units, was administered intravenously and the vessels occluded. Longitudinal arteriotomies, 10 to 12 mm in length, 4 to 6 cm apart, were made in the vessels. Infernal velour grafts 6 mm in diameter and 4 to 6 cm in length were preclotted and their ends were cut obliquely. After placement of a mattress stitch at the acute angle of the anastomosis, the No. 6-0 polyprop¬ ylene suture was run as an eversible stitch up each side of the anastomosis and tied at the opposite end. The bypassed arterial segment was doubly ligated immediately adjacent to the anasto¬ mosis. Anticoagulation was reversed with 15 mg of protamine sulfate on release of occluding clamps. Penicillin G benzathine, 600,000 units, was administered intramuscularly on the day of

operation. The dogs were serially placed in one of three groups (control, steroid, and immunosuppression) and observed for eight weeks.

The control group received no medication. The steroid group received methylprednisolone sodium succinate, 1 mg/kg intramus¬ cularly every other day, and the immunosuppression group received azathioprine, 1 mg/kg orally daily. The drug regimens were started on the first postoperative day. After killing the dogs, the grafts were removed and opened longitudinally. The internal diameters of the proximal and distal anastomotic lumens were measured with millimeter calipers. The differences in diameter were subjected to statistical analysis by analysis of variance. Finally, the grafts were stained with hema¬ toxylin-eosin and hexachrome for histologie examination. The

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Fig 1.—Photomicrograph of histology of anastomotic intimai hyperplasia. Control is dominated by mature collagen, little mucopolysaccharide substance, rare fibroblasts, and rare elastic fibers (trichrome stain, original magnification 100).

Fig 2.—Photomicrograph of histology of anastomotic intimai hyperplasia with methylprednisolone. Dominated by mucopoly¬ saccharide ground substance and fibroblasts, thin collagen, and few elastic fibers (trichrome stain, original magnification X100).

histologie appearance of the tissues found at the anastomotic sites in the different groups was recorded with specific attention placed on

any cellular differences.

RESULTS

Patency In the control group, 14 of 20 grafts were patent at death yielding a 70% eight-week patency rate. There were no wound complications in this group. The group treated with steroids had exactly the same eight-week patency rate, namely, 70% (14 of 20). No wound complications occurred. The group that received immunosuppression had a 100% eight-week patency rate with 20 of 20 grafts open. One dog in this group had bilateral draining hematomas at 24 hours postoperation and, despite antibiotic coverage and reexploration for evacuation and hemostasis, the graft became infected, with a resultant suture erosion and exsanguination. Since this occurred five days postopera¬ tively, this dog was not used in calculation of the data. One other wound in this group became superficially infected but resolved without drainage. The grafts that were widely patent with insignificant anastomotic narrowing had no mural thrombus and a glistening smooth lining. The grafts that had moderate anastomotic narrowing exhibited no mural thrombus or varying degrees of mural thrombosis throughout the length of the graft without a visible smooth lining surface. The occluded grafts were divided into two morphological categories. Those with a noticeably stenotic area at the anastomoses and filled with thrombus were presumably classified as late graft failures. The grafts that were totally shrunken and whose center was composed of only fibrous tissue were considered to be early graft failures. Anastomotic Measurements

The internal diameter in the control group averaged 2.85 mm for 20 grafts in which zero diameter was assigned to thrombotic grafts. The distal internal diameters were slightly greater at 3.37 mm and the average diameter for

Fig 3.—Photomicrograph of histology of anastomotic intimai hyperplasia with azathioprine. Dominated by mucopolysaccha¬ ride ground substance, moderate number of fibroblasts and elastic fibers, and thin collagen (hematoxylin-eosin, original magnification 100). all control anastomoses considering proximal and distal together was 3.11 mm. The steroid-treated grafts had similar internal diameters, with 3.08 mm proximally, 3.29 distally, and combined diameter of 3.19 mm. The immunosuppression-treated grafts, which were all patent, had equal proximal and distal internal diameter at 5.42 mm and

5.43 mm, respectively. The patent grafts were then considered separately, thus, excluding any technical anastomotic problem that may have led to early graft failure. In the control group, the internal diameter of the proximal anastomosis was 4.07 mm. The steroid-treated grafts had similar diameters with 4.40 mm proximally, 4.70 mm distally, and a 4.55-mm

combined diameter (Table 1). Using the analysis of variance technique to analyze substantial differences, it was found that the internal diameter of either the proximal or distal anastomoses of the steroid group was not statistically different from the

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plasia

Table 1.—Anastomotic Internal Diameters

Combined, Proximal,

mm

Distal,

mm

mm

All Grafts"

Control Steroid Immunosuppression

2.85

3.37 3.29

Steroids and immunosuppression. Effect on anastomotic intimal hyperplasia in femoral arterial dacron bypass grafts.

Steroids and Immunosuppression Effect on Anastomotic Intimal Hyperplasia in Femoral Arterial Dacron Bypass Grafts Lawrence M. Hoepp, MD; Ahmad Elbad...
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