Intragraft drug infusion as an adjunct to balloon catheter thrombectomy for salvage of thrombosed infragenicular vein grafts: A preliminary report Daniel B. Walsh, MD, Robert M. Zwolak, MD, PhD, Martha D. McDaniel, MD, Joseph R. Schneider, MD, and Jack L. Cronenwett, MD, Hanover, NJ-I. Early infragenicular vein graft thrombosis is associated with poor secondary patency, particularly when no correctable defect is identified. We have attempted to improve patency of thrombosed vein grafts by direct infusion of vasodilator and anticoagulant drugs after surgical thrombectomy. Among 212 infragenicular vein grafts, 16 (7.5%) required thrombectomy within 30 days of surgery (14 in situ saphenous vein, 1 composite vein, and 1 cephalic vein graft). Causes for failure were corrected in four (graft twist, intimal tear, suture failure, and external compression), resulting in prolonged patency. No cause for failure was apparent in the 12 remaining grafts after balloon catheter thrombectomy and arteriography. Two of these grafts occluded within 10 days despite multiple attempts at vein patch angioplasty, distal graft extension, and repeat thrombectomy with systemic anticoagulation. In the remaining 10 grafts, a small polyethylene catheter was placed in a proximal vein branch for direct intragraft drug infusion. Heparin (10 units/min) and nitroglycerin (50 Izg/min) were the agents infused most frequently, for a mean duration of 52 hours after thrombectomy. Of these 10 infused grafts, 8 remained patent during a mean 17-month follow-up (range, 6 to 38 months). This w a s accomplished despite previous and repeated failures of thrombectomy and systemic anticoagulation in seven of these eight grafts. Two infused grafts rethrombosed within 30 days of infusion, resulting in amputation. No catheter-related complications occurred. Increased thrombogenicity, intimal injury, and spasm after balloon catheter thrombectomy may contribute to vein graft rethrombosis in the absence of technical defects. Direct intragraft infusion of nitroglycerin and heparin contributed to prolonged salvage of 80% of thrombosed vein grafts in this preliminary experience. (J VAse SuRG 1990;11:75360.) Successful autogenous vein grafts to the tibial, l~7_;oneal, and pedal arteries are now commonplace. Advances in vascular surgery have reduced early occlusion rates of these infragenicular vein grafts to less than 10%. Despite these improvements, however, there appears to be a residual 5% to 10% early (30day) failure rate, which may be the result of not only technical errors or limited distal runoff but also coagulation defects and other problems that are not recognizable at reoperation. Although the prognosis

From the Section of Vascular Surgery, Dartmouth-Hitchcock MedicalCenter. Presentedat the SixteenthAnnualMeetingof the New England Societyfor VascularSurgery,BrettonWoods, N.H., Sept. 2122, 1989. Reprint requests:DanielB. Walsh,MD, Departmentof Surgery, Dartrnouth-HitchcockMedicalCenter, Hanover,NH 03756. 24/6/19433

for vein graft thrombosis is poor, reexploration to restore graft flow is usually undertaken, especially when graft thrombosis is recognized early. In addition to correcting any technical problem, balloon catheter thrombectomy is usually required. With reversed saphenous vein grafts, thrombectomy is complicated by valve cusps that prevent atraumatic retrograde passage of the balloon catheter. Although in situ vein grafts with lysed valves facilitate balloon catheter thrombectomy, considerable intimal trauma still results. Thrombolytic therapy has been suggested for the management of vein graft thrombosis, but its use in the immediate postoperative period is often precluded by the danger of bleeding complications, and the necessity for graft reexploration to correct a treatable, technical flaw usually dictates an operative approach. There is little published experience concerning the outcome of operative treatment of early vein graft 753

754 Walsh et al.

thrombosis. Anecdotal experience indicates that such attempts are often unsuccessful. During the past 3 years, we have employed a technique of continuous intragraft drug infusion after balloon catheter thrombectomy in an attempt to prevent early rethrombosis. This technique is based on the hypothesis that distal arterial and vein graft spasm, plus platelet and fibrin deposition, may best be prevented by direct infusion of appropriate agents. In this report we describe our initial experience in 10 such cases. PATIENTS A N D METHODS Between January 1986 and December 1988, 212 infragenicular arterial reconstructions with autogenous vein were performed at the DartmouthHitchcock Medical Center. Of these grafts, 16 (7.5%) occluded within 30 days of operation. The medical records of these 16 patients were reviewed to summarize our recent experience with the management of early vein graft thrombosis. Among these 16 patients whose infragenicular vein grafts failed, 11 were men and 5 were women, with an average age of 67 years (range, 29 to 95 years). Two of these operations were performed to relieve claudication, 2 to treat popliteal aneurysms, and the remaining 12 for rest pain or tissue loss. Only 4 patients were diabetic. Five bypasses in this group were performed to the infragenicular popliteal artery. The remaining 11 used tibial or peroneal vessels as bypass recipients. The venous conduit was in situ saphenous vein in 12 patients, composite saphenous-cephalic vein in 3 patients, and reversed cephalic vein in 1 patient. Operative techniques used for the initial vein bypass were Similar in all patients. Valves of in situ saphenous vein grafts were lysed with retrograde valvulotomy done through side branches of the entirely exposed vein. Intraoperative completion arteriography was performed routinely to assess the quality of the vein graft, the technical appearance of the distal anastomosis, recipient vessel runoff, and, in the case of nonreversed veins, the adequacy of valve lysis and vein branch ligation. All anastomoses were constructed by loupe magnification with heparin anticoagulation during arterial occlusion. Doppler examination of the graft and distal limb circulation was performed during surgery and frequently during the early postoperative period. If graft failure was suspected by history or physical examination and confirmed by Doppler or duplex examination, patients underwent urgent anticoagulation with heparin and were returned to the operating room. Usually the distal anastomosis was explored

Journal of VASCULAR SURGERY

first. More proximal graft explorations were p~tformed when required, based on operative findings. Balloon catheter thrombectomy and intraoperative angiography were employed to reestablish graft patency and determine the cause of graft failure. All failed grafts occluded within 14 days of operation. Fourteen of the 16 thromboses were detected within 5 days of operation. Surgically correctable causes for graft thrombosis could be identiffed in only four patients. Two of these patients were found to have twists within the grafts that were revised by rerouting the graft or revising the distal anastomosis. In the third patient an intimal tear caused by the valvulotome led to thrombosis on postoperative day 14 and was repaired with a vein patch venoplasty. The polypropylene suture at the distal anastomosis had broken in the fourth patient causing anastomotic disruption. A compressive hematoma was evacuated and the anastomosis repaired. In each instance the graft underwent concurrent bal!.~r catheter thrombectomy. No patient in this group underwent anticoagulation after thrombectomy. Twelve of the 16 thrombosed vein grafts had no identifiable defects at reoperation, despite evaluation by arteriography, direct visual inspection, or angioscopy. Two of these patients were managed before introduction of intragraft drug infusion. The first patient, a 95-year-old woman with rest pain, underwent thrombectomy of a femoral to infragenicular popliteal artery bypass with composite saphenous vein graft that thrombosed on postoperative day 4. No technical problem was discovered. The venotomy was closed with a vein patch. When this failed 4 days later, she was returned to the operating room. For the second time no technical flaw was seen. Her graft was extended with an interposition vein graft i ~ ) n attempt to improve runoff. Despite systemic anticoagulation with heparin, the graft again thrombosed and no further efforts were made at revascularization. The other patient treated without intragraft infusion had undergone in situ saphenous vein bypass to exclude a popliteal aneurysm. This graft thrombosed twice within 24 hours of operation. After each failure, a balloon catheter thrombectomy was performed immediately and systemic anticoagulation was continued. Although no technical problems were found, the distal anastomosis was revised each time with a vein patch. After failure of the second revision, the foot was viable and further attempts at graft salvage were deferred because of the patient's precarious cardiac status. In the subsequent 10 patients who had graft thrombosis with no apparent cause, intragraft drug

Volume 11 Number 6 June 1990

Vein graft salvage with intragraft drug infusion 755

Fig. 1. For direct intragraft drug infusion a 20-gange polyethylene catheter was placed into a side branch of the vein graft and secured so that its end did not project into the graft lumen.

infusion was used as an adjunct to balloon catheter thrombectomy (Table I). Six of these 10 grafts thrombosed immediately after the initial operation, whereas the remaining 4 failed from I to 8 days after operation. Graft infusion catheters were placed in only 2 of the 10 patients at the time of the initial thrombectomy (Nos. 7 and 9, Table I). In the other eight patients the infusion catheter was not inserted m~dl the first thrombectomy failed (and in three patients until after the second thrombectomy failed). Thus 8 of the 10 patients underwent multiple failed attempts at conventional thrombectomy and systemic anticoagulation before a graft infusion catheter was placed. Six of these eight patients underwent adjunctive procedures such as papaverine infusion, vein patch angioplasty, questionable valve cusp lysis, or intraoperative urokinase infusion during the initial reexploration (Table I). In contrast to the four patients described above in whom a definite surgical defect was found, none of these adjunctive measures was believed to be definitive treatment but was performed to eliminate minor or potential problems. During the reexploration that involved catheter placement, only one patient, whose graft had previously thrombosed twice, underwent any further operative graft revision, this being a vein patch angio-

plasty of the distal anastomosis. In two patients, urokinase was infused during surgery after thrombectomy but before catheter placement in an attempt to remove residual intragraft thrombus. When the technique of continuous intragraft infusion was used, a 20-gauge polyethylene catheter was placed into a convenient side branch of the proximal vein graft. The catheter was secured with silk ligatures so that its end was in the branch orifice but did not enter the main-flow channel (Fig. 1). The catheter was passed through a separate skin puncture, secured, and attached to a controlled infusion device. As shown in Table I, infusion drugs and doses varied among our patients. In the nine patients who received heparin, the mean dose was 590 units/hr (range, 250 to 1000 units/hr). Nitroglycerin was infused at a mean rate of 4.5 mg/hr (range, 2.5 to 6 mg/hr). As our experience progressed, we chose infusion rates of 10 units/min of heparin and 0.05~g/min of nitroglycerin. Patients were monitored in the postanesthesia or intensive care units during infusion. All catheters were removed easily with a local anesthetic either in the operating room or at the bedside. Follow-up data were collected at the time of the most recent outpatient evaluation. Grafts were con-

756

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Walsh et al.

Table I. D a t a s u m m a r y for 10 failed inftagenicular vein grafts given intragraft infusion Age~sex (yr)

Symptom

Diabetes mellitus

Graft type

Recipient vessel

1

61/M

Rest pain

I

IS

PT

2

66/M

Rest pain

N

IS

AT, PT

3

63/M

Rest pain

N

IS

PT

4

65/M

Tissue loss

I

IS

PT

5

85/M

Tissue loss

N

IS

P

6

73/F

Rest pain

N

RC

PT

7

57/F

Tissue loss

I

IS

PT

8

29/M

Tissue loss

N

IS

AT

9

80/M

Tissue loss

N

IS

PT

10

76/F

Rest pain

II

IS

IP

Pt. No.

Salvageprocedure (postoperativeday)

Infusion agent duration (hr)

Thrombectomy, cusp lysis (1); thrombectomy, catheter placed (2) Thrombectomy, intraoperative urokinase (0); thrombectomy, catheter placed (0) Thrombectomy, vein patch (0); thombectomy, intraoperative urokinase (0); thrombectorny, catheter placed (0) Thrombectomy (3); thrombectomy, catheter placed (5) Thrombectomy, papaverine injected (0); thrombectomy, anticoagulation (0); thrombectomy, catheter placed (8) Thrombectomy; vein patch (0); thrombectomy, catheter placed (0) Thrombectomy, catheter placed (0) Thrombectomy (0); thrombectomy, catheter placed (2) Thrombectomy, angioscopy, vein patch twice, intraoperative urokinase, catheter placed (2) Thrombectomy; thrombectomy, vein patch (0); thrombectomy, vein patch, catheter placed (1)

LMD (50 ml/hr) 77 Hep (1000 units/hr), Pap (2 mg/hr) NTG (6 mg/hr), 184 Hep (500 units/hr)

Highest l ~ T (see)*

38

40

NTG (3.3 mg/hr), 41 Pap (60 mg/hr)

27

NTG (4.5 mg/hr), 22 Hep (800 units/hr)

112

NTG (5.3 mg/hr), 19 Hep (900 units/hr)

>120 "

NTG (6 mg/hr), 7 Hep (600 units/hr)

NA

NTG (6 mg/hr), 39 Hep 500 tmits/hr) NTG (2.5 mg/hr), 40 Hep (500 units/hr)

55 42

NTG (2.5 mg/hr), 56 Hep (250 units/hr)

38

NTG (3 mg/hr), 30 Hep (275 units/hr)

65

PTT, Partial thromboplastin time; I, insulin dependent; IS, in situ; PT, posterior tibia]; LMD, low molecular-weight dextran; Hep, heparin; Pap, papaverine; ABI, ankle/brachial index; BKA, below-knee amputation; v, not diabetic; AT, anterior tibial; NTG, nitroglycerin; LS, limb salvage; Pr, peroneal; RC, reversed cephalic; NA, not available; II, non-insulin-dependent; IP, infrapopliteaL Normal: 25 to 33 seconds.

sidered patent if confirmed by duplex scanning or if the patient was symptomatically i m p r o v e d with an ankle-brachial index ---0.15 higher than that before surgery. RESULTS In the four cases in which a definite surgically correctable cause for vein graft thrombosis was

found, all grafts remained patent during a m e a n follow-up o f 13 m o n t h s (range, 5 to 26 months). In the t w o patients in w h o m n o technical error was f o u n d and n o intragraft infusion was used, both grafts p r o m p t l y occluded, resulting in below-knee a m p u t a t i o n in one and persistent ischemia with severe claudication in the other patient. Eight o f 10 patients w h o u n d e r w e n t intragraft

Volume 11 Number 6 June 1990

30-Day patency (technique)

Vein graft salvage with intragraft drug infusion 757

Function at last follow-up Technique

Duration

Outcome

Yes (ABI)

Occluded

20 Mo

BKA

Yes (ABI)

Patent (duplex)

38 Mo

LS

Yes (duplex)

Patent (duplex)

26 Mo

LS

Yes (duplex)

Occluded (duplex)

18 Mo

LS

Yes ~duplex)

Patent (ABI)

13 Mo

LS

No (ABI)

Occluded

10 Days

BKA

Yes (duplex)

Patent (duplex)

5 Mo

LS

No (duplex)

Occluded (duplex)

28 Days

BKA

Yes (duplex)

Patent (duplex)

7 Mo

LS

Ye~ (duplex)

Patent (duplex)

7 Mo

LS

drug infusion had patent grafts at 30 days by duplex examination. Six of these are currently patent after a mean follow-up of 16 months (range, 5 to 38 months). One graft failed after 20 months, leading to rest pain and below-knee amputation performed elsewhere without attempted revascularization. One graft occluded after 18 months, leading to rest pain in a patient who declined further intervention. Thus 8 of 10 patients have achieved a mean patency of 17 months after adjunctive intragraft drug infusion. This

technique failed to achieve 30-day graft patency in only 2 of the 10 patients, and both failures led to below-knee amputation. One of these patients had extremely poor outflow as a result of thromboangiitis obliterans distal to the recipient vessel, an isolated segment of the anterior tibial artery. His graft thrombosed 24 days after surgery. The second failure occurred immediately after a reversed cephalic vein bypass to a small, distal posterior tibial artery with no apparent pedal arch. Graft failure was attributed to inadequate outflow in both cases. There were no complications attributable to infusion catheter placement. Although all patients required postoperative blood transfusion, it was impossible to isolate the contribution of the catheter infusion agents, because these patients also underwent multiple operations contemporaneously with catheter placement. No bleeding, hematoma formation, infection, or other incisional complication occurred at the site of catheter placement. DISCUSSION Early failure of infragenicular vein bypass grafts has been reduced in recent years by meticulous attention to technical detail and intraoperative graft evaluation by artetiography. 14 Angioscopy and intraoperative duplex evaluation may improve early patency further when compared with completion arteriographyY However, these studies suggest that 5% to 10% of infragenicular vein grafts still thrombose within 30 days of implantation. This small percentage of failures may be irreducible if patients with poor vein or inadequate outflow are offered limb salvage procedures. However, evidence would suggest that not all grafts fail as a result of vein or outflow inadequacy and salvage attempts may be worthwhile at least in some patients. In their review of the cause of lower-extremity bypass graft failures, Stept et al.s concluded that indeterminable factors accounted for 48% of early thromboses. Indeterminable may imply biologic rather than mechanical factors, whereby patency is threatened by problems not visible on completion arteriograms. These biologic effects may include localized vasospasm; intimal injury from damping, instrumentation, or arteriography; and enhanced thrombogenicity of the flow surface after thrombosis.9,1° However, recognition of these factors has not been associated with major improvement in the salvage of thrombosed vein grafts, which historically has been quite poor. Whittemore et al.~l evaluated 18 patients with saphenous vein bypass grafts who underwent thrombectomy and vein patch angioplasty after thrombosis

758 Walsh et al.

and found only a 19% cumulative 5-year patency rate. This series was updated by Cohen et al.12 with the addition of seven patients and a cumulative 5year patency rate of 28%. The early rethrombosis rate was not cited in this report, and few published data are available with which to compare our results with intragraft infusion. This is especially true in patients who had no surgically correctable defect responsible for graft failure. Several authors have reported initial success with intragraft thrombolytic therapy as a treatment for thrombosed vein grafts. An initial report by Hargrove et al.13 noted successful recanalization in four grafts treated with low-dose intragraft streptokinase supplemented with transluminal angioplasty. After this report, early success rates for thrombolytic therapy in thrombosed vein grafts have been reported from 11% to 55%. ~417 None of these reports addressed long-term outcome, however, and no patient in these series was treated in the early postoperative period, when bleeding from incisions may complicate thrombolytic infusion. We were initially stimulated to attempt direct intragraft pharamcologic therapy based on our poor results in patients with early vein graft occlusion in cases in which no surgically correctable causc was found. This experience is exemplified by the two patients described in this report who failed multiple attempts at thrombectomy and systemic anticoagulation before our introduction of graft infusion. We have frequently observed incisional hematoma formation associated with systemic heparin therapy after thrombectomy and, despite this, found that grafts rethrombosed. Therefore we attempted to use a heparin dose adequate to achieve local anticoagulant effects but low enough to prevent bleeding complications. We added vasodilating agents with the goal of reducing distal arterial or vein graft spasm and increasing graft flow rate by decreasing peripheral resistance in the recipient vascular bed. We were encouraged to attempt this technique based on our previous animal studies that demonstrated that intraarterial infusion of a stable prostacyclin analog improved polytetrafluoroethylene graft patency and reduced graft-platelet deposition. TM Because prostacyclin analogs are not yet clinically approved for this indication, we selected currently available agents to achieve antiplatelet and vasodilating effects. Previously, Dickerman et a139 had demonstrated and Peck et al.20 had confirmed the benefit of continuous vasodilator infusions to relieve arterial spasm in patients who had sustained trauma. Samson et al. 2~

Journal of VASCULAR SURGERY

described the usefulness of vasodilator bolus infusions for the treatment ofvasospasm after distal lower extremity arterial revascularization. We ultimately selected nitroglycerin because of its combined vasodilating and antiplatelet properties and its tolerance by these patients. Nitroglycerin has been shown to decrease the vasoconstrictive response associated with arterial wall injury, in a manner consistent with its endothelium-independent vasodilator properties. 22-2~Theoretically, nitroglycerin can prevent vasoconstriction in both the recipient artery and the vein graft. The opportunity to reduce local thrombus formation and vasoconstriction in the vein graft by heparin and nitroglycerin is the rationale for selecting a proximal branch of the vein graft as the preferred site for catheter placement. 2s In vivo and in vitro studies dispute whether nitroglycerin can enhance endothelial prostacyclin synthesis and inhibit platelet thromboxane A2 production. 26-sl However, nitroglycerin does decrease platelet deposition in:~h~ ' early postoperative period, particularly in patients who have depleted plasma stores of reduced thiols (N-acetylcysteine), such as patients who have taken nitrates chronically.32 The relative contributions of the vasodilatory and antiplatelet properties of nitroglycerin in this situation are as yet unknown. Heparin and nitroglycerin are not necessarily the most appropriate infusional agents. In patients who have sustained trauma, tolazoline has been used with success.19'2° Prostacyclin analogs have great theoretic appeal because of their antiplatelet and vasodilating properties. Prolonged chronic local infusion of thrombolytic agents in the postoperative period could also be performed through an intragraft catheter to eliminate distal thrombus, with caution concerning the integrity of the distal anastomosis. ~.n additional advantage of the intragraft catheter is the ability to inject radiopaque contrast material sufficient to obtain high-quality digital subtraction arteriograms after surgery, when incisions may otherwise complicate conventional arteriographic puncture. We are encouraged by our initial experience with the adjunctive use of intragraft infusion of nitroglycerin and heparin, which achieved vein graft salvage in 8 of 10 patients in whom no surgically correctable cause for graft failure could be found. Although this initial experience was not randomized or controlled, the fact that six of eight salvaged grafts had failed twice before catheter placement adds credence to the conclusion that intragraft drug infusion had significant efficacy. However, conclusions from

Volume 11 Number 6 June 1990

~nis series must be limited. The number of patients is small, and the population was clearly selected. The infusional agents employed and the infusion intervals chosen were not uniform. Although we do not believe that operative measures employed in conjunction with continuous infusions were critical for success, we cannot prove this conclusion. Because of the infrequency of this problem, a large randomized study is impractical. However, in our experience this technique appears valuable in otherwise desperate situations. REFERENCES 1. Hall KV. The great saphenous vein used "in situ" as an arterial shunt after extirpation of the vein valves. Surgery 1962; 51:492-5. 2. Taylor LM Jr, Edwards JM, Porter JM, Phinney ES. Reversed vein bypass to infrapopliteal arteries: modern results are superior to or equivalent to in situ bypass for patency and for vein utilization. Ann Surg 1987;205:90-7. 3 Leather RP, Shah DM, Chang BB, Kaufman JL. Resurrection of the in situ saphenous vein bypass: 1000 cases later. Ann Surg 1988;208:435-42. 4. Rutherford RB, Jones DN, Bergentz SE, et al. The efficacy of dextran 40 in preventing early postoperative thrombosis following difficult lower extremity bypass. J VASC St:WG 1984;1:765-73. 5. Liddicoat JE, Bekassy SM, DeBakey ME. Intraoperative arteriography during femoral-popliteal bypass. Arch Surg 1975;110:839-40. 6. Miller A, Campbell Dr, Gibbons GW, et al. Routine intraoperative angioscopy in lower extremity revascularization. Arch Surg 1989;124:604-8. 7. Bandyk DF. Intraoperative color flow imaging of difficult arterial reconstructions. Presented at Intraoperative Adjunctive Procedures, the Society for Vascular Surgery, New York, June 21, 1989. 8. Stept LL, Flinn WR, McCarthy WJ III, Bartlett ST, Bergan JJ, Yao JST. Technical defects as a cause of early graft failure after femorodistal bypass. Arch Surg 1987;122:599-604. 9. Bech FR, Gait SW, Cronenwett JL. Increased platelet deposition on PTFE grafts after balloon catheter thrombectomy. J VASCSURG1990;11:804-11. 10. Walsh DB, Dubiansky V, Nauta RJ, Ahrned SW, Butterfield AB, Goldstein HA. Assessment of graft harvest trauma by fight microscopy, platelet adherence and contractile tension. Presented at the Eighteenth World Congress of the International Society of Cardiovascular Surgery, Sydney, Australia, September 1987. 11. Whittemore AD, Clowes AW, Couch NP, Mannick JA. Secondary femoropopliteal reconstruction. Ann Surg 1981; 193:35-42. 12. Cohen JR, Mannick JA, Couch NP, Whirtemore AD. Recognition and management of impending vein-graft failure. Arch Surg 1986;121:758-9. 13. Hargrove WC, Berkowitz HD, Freiman DB, McLean G, Ring EJ, Roberts B. Recanalization of totally occluded fern-

Vein graft salvage with intragraft drug infusion 759

14. 15.

16.

17. 18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

oropopfiteal vein grafts with low-dose streptokinase infusion. Surgery 1982;92:890-5. Sicard GA, Schier JJ, Torty WG, et al. Thrombolytic therapy for acute arterial occlusion. J VASe SURG 1985;2:65-78. van Breda A, Robison JC, Feldman L, ct al. Local thrombolysis in the treatment of arterial graft occlusions. J VAse SURG 1984;1:103-12. Sniderman KW, Kalman PG, Shewchun J, Goldberg REA. Lower-extremity in situ saphenous vein grafts: angiographic interventions. Radiology 1989; 170:1023-7. Gardiner GA Jr, Koltun W, Kandarpa K, et al. Thrombolysis of occluded femoropopliteal grafts. AJR 1986; 147:621-6. Dacey LJ, Hees P, Cronenwett JL. Intra-arterial 9-[3-methyl carbacyclin improves canine polytetrafluoroethylene graft patency. J VAse SUKG 1988;8:21-7. Dickerman RM, Gewertz BL, Foley DW, Fry WJ. Selective intra-arterial tolazoline infusion in peripheral arterial trauma. Surgery 1977;81:605-9. Peck JJ, Fitzgibbons TJ, Gaspar MR. Devastating distal arterial trauma and continuous intraarterial infusion of tolazoline. Am J Surg 1983;145:562-6. Samson RH, Gupta SK, Scher LA, Veith FJ. Arterial spasm complicating distal vascular bypass procedures. Arch Surg 1982;117:973-5. Lain JYT, Chesebro JH, Fuster V. Platelets, vasoconstriction, and nitroglycerin during arterial wall injury: a new antithrombotic role for an old drug. Circulation 1988;78: 712-6. Ignarro LJ, Lippton H, Edwards JC, et al. Mechanisms of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 1981;218:739-49. Rapoport RM, Murad F. Agonist-induced endotheliumdependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res 1983;52:352-7. Walsh DB, Butterfield AB, Nanta RJ, et al. Effects of vein valve treatment on graft contractility and patency. Surg Res Commun 1988;5:193-203. Schafer AL, Alexander RW, Handin RI. Inhibition ofplatelet fianction by organic nitrate vasodilators. Blood 1980;55:64954. Levin RI, Jaffe EA, Weksler BB, Tack-Goldman K. Nitroglycerin stimulates synthesis of prostacyclin by cultured human endothelial cells. J Clin Invest 198i;67:762-9. Schror K, Grodzinska DH. Stimulation of coronary vascular prostacyclin and inhibition of human platelet thromboxane Az after low-dose nitroglycerin. Thromb Res 1981;23: 59-67. Stamler J, Cunningham M, Loscalzo J. Reduced thiols and the effect of intravenous nitroglycerin on platelet aggregation. Am J Cardiol 1988;62:377-80. Mehta J, Mehta P. Comparative effects of nitroprusside and nitroglycerin on platelet aggregation in patients with heart failure. J Cardiovasc Pharmacol 1980;2:25-33. Lichtenthal PR, Rossi EC, Louis G, et al. Dose-related prolongation of the bleeding time by intravenous nitroglycerin. Anesth Analg 1985;64:30-3. Loscalzo N. N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin. J Clin Invest 1985;76: 703-8.

760

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Journal of VASCULAR SURGERY

DISCUSSION Dr. A n t h o n y D. Whittemore (Boston, Mass.). The technical cause of early failures has been well documented. Notable among those causes for failure that we were able to identify in our study in 1981, technical errors accounted for about 18%. This same failure rate has now diminished, which reflects several factors including improved technique and the use of completion angiography. The persistent 5% to i 0 % early failure rate documented in this series occurs for several reasons. A group of hypercoagulable patients seems to be emerging, and a number of grafts failed for unknown reasons including venous spasm and minor intimal tears. Our own experience demonstrated that the cause of vein graft failure remains tmdetermined in about about 30% of these patients. We are sure that some these failed early because of a variety of hypercoagulable states. The fact that 80% o f these grafts that initially failed in this series subsequently had restored patency and have remained patent for 1 year is gratifying, as is the notable lack of complications sustained in their series. These results are particularly impressive because six of the eight successfully treated grafts underwent multiple previous thrombectomies or revisions before their being infused. Were you able to identify any susceptibility to hypercoagulability in any of these patients? Were you able to screen them? Did you find any of these syndromes existent? Second, what are the potential advantages or hazards of incorporating low-dose thrombolytic therapy in the same infusion? Is there any role for urokinase or tissue plasminogen activator or do you think we should allow the endogenous thrombolytic system to proceed at its own pace? Do you think that this protocol should be adopted on a routine basis? I suspect not, but is there any way we can select the patients whose grafts are most likely to fail so you could use this prospectively and avoid the midnight returns to the operating room? Dr. Thomas O'Donnell (Boston, Mass.). Several years ago we presented to this Society our results with early in situ graft failure. The cause of these failures early in your experience with in situ bypass was predominantly technical in practically 70% of cases. Retained valves, external compression, redundancy, and kinking were technical factors for early failure. As our experience with the technique has increased, this technical reason for failure certainly has decreased and we are left with a group of patients whose grafts fail for unknown reasons. Presumably in these patients, outflow resistance plays a role (i.e., the same concept that outflow is too high to accept inflow). Are we in any way able before or during surgery to assess resistance to blood flow in these patients? Second, are there any angiographic criteria in these patients that might suggest why these grafts fail versus the patients whose grafts remain patent? Finally. like Dr. Whittemore, I would like

to know whether you believe that lyric therapy, particularly urokinase, is helpful for not only chemical thrombectomy of the graft but also opening distal thrombosed arteries beyond your anatomosis and hopefully decreasing outflow resistance? Dr. F. B. Pomposelli (Boston, Mass.). Some patients with early graft thrombosis for unexplained reasons may have failed grafts because the runoffwas occluded distally, which was not appreciated on the preoperative cut-film angiogram. H o w do you study your patients for distal bypass? Do you do routine digital studies of the distal outflow? Also, would you bypass into an isolated tibial segment intentionally, or will you go lower to ensure continuity with the pedal vessels? Dr. Gary Gibbons (Boston, Mass.). When we anticipate a prolonged procedure, we place a Marks irrigating needle in the first proximal vein branch and gently instill heparinized papaverine solution while we are lysing the valves. We are irrigating the vein graft while we are d~"~.g, the procedure. Have you considered doing anything like that during these procedures? Dr. D. B. Walsh (closing). We have not in any formal way studied hypercoagulability in this group of patients. Unfortunately, the numbers of these patients are so small, given the size of the problem, that how they should be screened becomes an economic issue. In an informal examination we have not found any clues as to who is going to have a problem. We have frequently infused lyric agents in thrombosed grafts and I think it is a useful technique. I see no reason why a localized infusion through the graft would be contraindicated. As far as I know, we have had no lyric-related complications. Unfortunately, lyric effects in this situation are hard to control. I have a patient in the hospital right now in whom we gave lyric therapy after multiple thromboses and thrombectomies. We saved his heel, but we did not save the distal part of the foot. E-% dorsal pedal circulation remained thrombosed in spite of thrombectomy and thrombolysis, whereas the posterior tibial circulation was patent. Unfortunately, he still lost his leg. In terms of measuring outflow resistance, we have not done it in a formal way. We have done it at times in some of these patients whose grafts have failed. We can tell by the Doppler, by the inability to advance Garrett dilators down the outflow vessels, that we are going to have a big problem. We have no angiographic criteria on patient selection. We always obtain visual substraction angiography. We will always try to go more distally into a patent runoff system rather than to an isolated segment tmless there is some other factor (i.e., no available vein). Certainly we advocate digital subtraction angiography in all these patients.

Intragraft drug infusion as an adjunct to balloon catheter thrombectomy for salvage of thrombosed infragenicular vein grafts: a preliminary report.

Early infragenicular vein graft thrombosis is associated with poor secondary patency, particularly when no correctable defect is identified. We have a...
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