Platelet antagonists eliminate thromboembolic complications of small-diameter arterial prostheses

An animal model suitable for study of the origin and method of prevention of thromboembolic complications of arterial prostheses has been developed in the rabbit. In phase I of the experiments 42 New Zealand white rabbits underwent insertion of polytetrafluoroethylene (PTFE) aortic grafts, 10 mm in length and of 2 mm internal diameter (I.D.) (n = 17) and 3 mm I.D. (n = 25). The patency rate at 3 months was 24% and 82%, respectively. Unexpected ischemic hind limb ulcers occurred in nine (38%) of the long-term survivors. Arteriograms in these animals showed a typical embolic occlusion of a distal artery, suggesting that the ulcers were due to embolization of loose mural thrombus, which was present in 50% of the grafts when removed. In phase II experiments 54 rabbits were randomly allocated to receive aspirin (ASA) 10 mg/kg/day and dipyridamole (DPM) 10 mg/kg/day (n = 25) or placebo (n = 29). Both regimens began 3 days before insertion of PTFE aortic grafts (10 mm long and 3 mm I.D.). Serum thromboxane B2 concentrations in the control group averaged 300.4 +/- 147.4 ng/ml and 43.2 +/- 58.6 ng/ml in the ASA/DPM group (p less than 0.0005). With the use of autologous indium 111 oxine-labeled platelets, a graft platelet accumulation index (GPAI) was calculated as the graft: reference ratio of emissions. ASA/DPM significantly reduced the mean GPAI calculated from grafts and reference aorta removed 48 hours after graft insertion from 69.3 +/- 4.0 on placebo (n = 4) to 34.3 +/- 2.9 (n = 4) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of platelet deposition on polytetrafluoroethylene grafts by antiplatelet agents

The effects of ibuprofen (Motrin), dipyridamole (Persantine), and prostacyclin on the deposition of platelets on polytetrafluoroethylene grafts (5.5 cm long, 4 mm internal diameter implanted into both femoral arteries of 21 dogs) were studied by harvesting autologous platelets, labeling them with 51Cr, and reinjecting them 15 minutes before cross-clamping. Arterial flow was adjusted to 65 ml/min and monitored continuously. Ibuprofen (12.5 mg/kg) and dipyridamole (2.5 mg/kg) were each administered as a single intravenous injection in four dogs (eight grafts) and five dogs (10 grafts), respectively. Prostacyclin (50 ng/kg/min) was administered by continuous intravenous infusion in five dogs (10 grafts). Seven dogs (14 grafts) served as controls. Grafts were removed 2 hours after implantation, and radioactivity (counts per 10 minutes) was determined in four segments of each graft (including both anastomoses) with a gamma-counter. Counts were averaged for each group of dogs. Significance was calculated by the Student t test. Platelet deposition in control dogs averaged 10,033.9 +/- 1134.2 SE; that in prostacyclin-treated dogs averaged 2513.7 +/- 276 SE (p less than 0.001); that in ibuprofen-treated dogs averaged 5453.4 +/- 1336.3 SE (p = 0.02); that in dipyridamole-treated dogs averaged 11,213.7 +/- 1632.5 SE (p = 0.55). These data demonstrate the effectiveness of prostacyclin and ibuprofen in reducing platelet deposition on polytetrafluorethylene grafts in dogs.     

Effects of thromboxane synthetase inhibition on patency and anastomotic hyperplasia of vascular grafts

The efficacy of a thromboxane synthetase inhibitor (U-63,557A, Upjohn) in promoting early patency and inhibiting anastomotic intimal hyperplasia in ePTFE grafts was compared to that of acetylsalicylic acid (ASA) in a canine model. Animals were started on ASA 5 gr po qd (Group I, n = 12) or U-63,557A 10 mg/kg po bid (Group II, n = 12) 1 day before placement of bilateral 5-mm-i.d., 13- to 16.5-cm-long ePTFE aortoiliac grafts and continued on the medication for the 16-week study. Six dogs in each group received autologous endothelial cell-seeded grafts, while the other six received unseeded grafts. Patency was determined weekly by assessment of femoral pulses. At the conclusion of the study anastomotic intimal hyperplasia was measured on serial sections through the distal anastomosis using a computer-linked digitizer. In Group I the patencies of seeded and unseeded grafts were not significantly different, being 100 and 83%, respectively. Furthermore, luminal narrowing due to intimal hyperplasia was not significantly different being 9.1 +/- 7.6% (chi +/- SD) in seeded grafts and 8.8 +/- 8.1% in unseeded grafts. On the other hand, in Group II the seeded grafts had significantly improved patency when compared to the unseeded grafts (83% vs 33%, P less than 0.05) and less luminal narrowing (11.4 +/- 11.1% vs 21.9 +/- 19.5%, P less than 0.01). Although U-63,557A administration promoted patency of unseeded grafts compared to no antiplatelet medication (0% patency), it was significantly less effective than ASA in improving patency (P less than 0.05) and inhibiting luminal narrowing (P less than 0.01).     

Intraarterial 9-beta-methyl carbacyclin improves canine polytetrafluoroethylene graft patency

This study examined the effect of 9-beta-methyl carbacyclin, a synthetic, stable prostacyclin analog, on canine polytetrafluoroethylene (PTFE) graft patency. Twenty-five dogs had 4 mm x 7 cm PTFE grafts implanted bilaterally into the femoral arteries. A subcutaneous infusion pump was used to deliver either saline solution (control) or 9-beta-methyl carbacyclin (Ciprostine) at 100 (CARB-100) or 200 ng/kg/min (CARB-200) through a femoral artery branch just proximal to one of the femoral grafts, with the contralateral graft serving as a noninfused control. Graft-platelet deposition (with 111In-labeled platelets) was measured between the fifth and seventh days, with patency determined on the seventh day. Dogs were classified as aggregators (AGG [+]) if the preoperative epinephrine-enhanced sodium arachidonate platelet aggregation was greater than 20%. CARB-200 infusion significantly improved ipsilateral graft patency (80%) compared with noninfused grafts (50%, p less than 0.05), or grafts in control and CARB-100 dogs (43%, p less than 0.05). Anastomotic platelet deposition was decreased bilaterally in CARB-200 dogs by 45% to 59% compared with CARB-100 and control dogs (p less than 0.05). With the exception of grafts infused with CARB-200, AGG (+) dogs had significantly lower graft patency (26%) than nonaggregator AGG (-) dogs (71%, p less than 0.01). CARB-200 infusion significantly improved graft patency in AGG (+) dogs (71%), compared with control and CARB-100-infused grafts (19%, p less than 0.025). Intra-arterial 9-beta-methyl carbacyclin improved early PTFE graft patency and inhibited platelet deposition in a severe canine model, independent of baseline platelet aggregation status, which also had an important effect on graft patency.     

Anastomotic arteriovenous fistulae--are they worth it?

An adjuvant distal arteriovenous fistula (ADAVF) has been claimed to increase arterial bypass graft flow and patency when run-off is poor but others have suggested that a patent fistula does not improve in distal limb perfusion. In 10 dogs, hind limbs were rendered ischaemic by proximal arterial ligations and then revascularised with vein grafts. In each dog an ADAVF was constructed on the left graft while the right was used as a control. Flow and pressure were measured in each graft and distal artery and the effect of temporary occlusion and release of the fistula noted. These measurements were repeated at re-operation 3 months later. Mean flow through control grafts was 83 +/- 8.57 (S.E.M.) ml/min, increasing to 146 +/- 22.89 (S.E.M.) ml/min with papaverine (P less than 0.001, Student's t test), and was unchanged at 3 months. Mean flow in grafts with a distal A-V fistula was 250 +/- 41.68 (S.E.M.) ml/min with no change after papaverine, and an increase to 730 +/- 110.5 (S.E.M.) ml/min at 3 months (P less than 0.001, Student's t test). However, arterial flow distal to the fistula was invariably retrograde at initial operation (20 +/- 3.0 S.E.M. ml/min), and this retrograde flow increased to 180 +/- 33.2 (S.E.M.) ml/min at 3 months (P less than 0.001, Student's t test). Distal arterial pressure at initial operation fell from 88.8 +/- 3.35 (S.E.M.) mmHg to 10.8 +/- 1.01 (S.E.M.) mmHg with the fistula open. We conclude that in this animal model an adjuvant distal arteriovenous fistula may improve bypass graft flow, but is unlikely to benefit distal limb perfusion.     

Does 111indium-platelet deposition predict patency in prosthetic arterial grafts?

The relationship between the rate of 111In-platelet deposition on vascular grafts and subsequent thrombosis has been examined in patients undergoing femoropopliteal by-pass. Sixty-seven patients undergoing femoropopliteal by-pass using vein, Dacron or PTFE were randomized to aspirin plus dipyridamole (ASA/DPM) or placebo. Autologous 111In-platelets were injected in the second postoperative week and Thrombogenicity Index (TI) calculated as the mean daily rise in the ratio of radioactivity graft/contralateral thigh. Graft patency was assessed to 1 year. Mean (+s.e.m.) TI at 1 week in 21 grafts that occluded within 12 months was 0.19 +/- 0.018 compared with 0.07 +/- 0.009 in the 38 that remained patient (P less than 0.001). Grafts with a TI less or greater than the median had a 90 per cent or 39 per cent cumulative 1-year patency, respectively (P less than 0.001). In the prosthetic grafts ASA/DPM reduced mean TI from 0.17 +/- 0.02 to 0.11 +/- 0.01 (P less than 0.02) and enhanced 1-year patency from 36 to 67 per cent (P less than 0.05). Following femoropopliteal by-pass TI related to subsequent graft patency. Radiolabelled platelet deposition therefore provides a guide as to how new materials or antithrombotic drugs may influence clinical graft thrombosis. Platelet inhibition reduced both graft thrombogenicity and subsequent occlusion.     

A self-sealing dialysis prosthesis. Coaxial double PTFE-silicone graft.

The performance of a new dialysis prosthesis designed to self-seal after puncture was tested ex vivo and in vivo. It consists of two coaxial polytetrafluoroethylene tubes (PTFE), the space between them filled with silicone rubber sealant (PTFE-sil). Ex vivo: Three PTFE-sil, three double PTFE (without silicone), and three single PTFE grafts were placed sequentially between scribner shunts in the hind limb of four dogs. Bleeding on puncturing with an 18-gauge needle was measured for 30 seconds. PTFE-sil bled less than the controls (g): PTFE-sil; 16 +/- 18; double PTFE: 32 +/- 10; single PTFE: 52 +/- 19 (p less than 0.001). In vivo: Six PTFE-sil and five single PTFE grafts were interposed between the carotid artery and jugular vein of dogs and were punctured with a 16-gauge needle on days 1, 3, and 7. Bleeding was measured through an incision over the puncture site at 5 minutes. In 11 punctures of PTFE-sil, there was no bleeding; three bled less than 20 g. In 13 control punctures, none bled less than 70 g. Patency: Grafts were studied for patency in arteriovenous (AV) fistulas in 34 dogs. Each dog received a PTFE-sil graft in one groin and a single PTFE control graft in the other. At 4 months, patency rates were: PTFE-sil, 84%; single PTFE, 87% (NS). Four months after implantation, hemostasis after puncture in PTFE-sil grafts required 70 +/- 49 seconds versus 207 +/- 48 seconds for PTFE grafts (p less than 0.005). In conclusion, PTFE-sil grafts are self-sealing, can be used immediately after implantation, and need minimal compression after needle removal.     

Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts

A pig model of autologous saphenous vein to common carotid artery bypass grafting was developed. An end-to-end anastomotic technique led to lower middle graft and distal turbulence. Saphenous veins were surgically prepared with or without distention at 600 mm Hg, implanted into the arterial circulation, and removed 2 hours later. Medial integrity was then assessed by adenosine triphosphate/adenosine diphosphate concentration ratio, and endothelial integrity, leukocyte and platelet adhesion by scanning electron microscopy. In grafts made with undistended vein adenosine triphosphate/adenosine diphosphate concentration ratio was not significantly lower (3.0 +/- 0.1, n = 32) than in freshly isolated vein (3.3 +/- 0.1, n = 26), endothelial cover was 98% +/- 1%, n = 6, and there was little platelet or leukocyte adhesion. In distended grafts adenosine triphosphate/adenosine diphosphate concentration ratio was reduced to 2.2 +/- 0.2 (n = 7, p less than 0.005), endothelial cover was reduced to 38% +/- 14% (n = 6, p less than 0.001), and there was extensive platelet and leukocyte adhesion to exposed subendothelium. In separate experiments graft patency measured at 1 to 5 weeks was significantly greater (96%, n = 25) when undistended vein was used than when distended vein was used (64%, n = 25, p less than 0.005). The data show that distention leads to medial and endothelial damage and that this is associated with increased platelet and leukocyte adhesion and with reduced early patency.     

Combined arachidonic acid and ADP platelet inhibition maximizes patency of small-diameter vascular grafts

Arachidonic acid (AA) and adenosine diphosphate (ADP) are potent stimuli of platelet aggregation. Each agonist may act through separate platelet pathways. In order to evaluate inhibition of ADP and AA on platelet aggregation, we studied the effect of ticlopidine (TC) and aspirin (ASA) alone and in combination on plasma thromboxane levels, platelet deposition, and patency of small-diameter vascular grafts in a canine model. Thirty-four mongrel dogs were classified as thrombosis prone (TP) or thrombosis resistant (TR) on the basis of in vitro platelet aggregation to AA. Four groups were studied: group I, control; group II, TC (100 mg/kg/day); group III, ASA (3 mg/kg/day); and group IV, TC/ASA (same doses). PTFE grafts were implanted bilaterally in the carotid and femoral arteries Ticlopidine inhibited in vitro platelet aggregation to both ADP and AA but had no significant effect on plasma thromboxane (Tx) B2 production. Aspirin inhibited AA-induced platelet aggregation and significantly decreased TxB2 production. Aspirin inhibited AA-induced platelet aggregation and significantly decreased TxB2 levels in both TP and TR animals (p less than 0.01). Although TC and ASA significantly inhibited platelet deposition and improved 1-month patency in both TP and TR animals, maximal patency was achieved in the group in which TC and ASA were combined. We conclude that platelet ADP and AA pathways are important determinants of the thrombogenic potential in vascular graft performance in dogs and that combined inhibition of both pathways achieves maximal vascular graft patency.     

Biventricular distribution of cold blood cardioplegic solution administered by different retrograde techniques

Although retrograde cardioplegia has been shown to provide adequate overall protection to the myocardium, delivery of cardioplegic solution to the right ventricle and septum is poor. We used an animal model of occlusion of the left anterior descending coronary artery to study the effects of modifying the conditions of retrograde cardioplegia administration on delivery to the right and left ventricles. Adult mongrel dogs (n = 12) were each given five retrograde injections of microsphere-labeled cardioplegic solution at 10-minute intervals. Four injections were made directly into the coronary sinus with ostial balloon occlusion at the following dosages and pressures: (1) 10 ml/kg at 30 mm Hg, (2) 20 ml/kg at 30 mm Hg, (3) 10 ml/kg at 50 mmHg, and (4) 20 ml/kg at 50 mm Hg. A fifth dose (20 ml/kg) was given directly into the right atrium at 50 mm Hg. Delivery of cardioplegic solution to the left and right ventricles was significantly reduced when the right atrial route was compared with the coronary sinus route at the same dosage and pressure (for left ventricle, 6.0% +/- 1.4% versus 22.7% +/- 11.4%/100 gm, p less than 0.001; for right ventricle, 0.7% +/- 0.2% versus 4.1% +/- 0.4%/100 gm, p less than 0.001). Septal delivery was less than that to the anterior and posterior left ventricle (10.4% +/- 1.3% versus 30.3% +/- 3.9% and 27.9% +/- 3.1%/100 gm, p less than 0.0001) for all injections. Delivery to the body of the right ventricle was less than that to the inflow and outflow tracts (1.8% +/- 0.2% versus 4.5% +/- 0.7% and 8.4% +/- 1.5%/100 gm, p less than 0.0001). These results indicate that, in this model, (1) the right atrial route provides less overall cardioplegic solution to both ventricles than direct retrograde coronary sinus cardioplegia and (2) regional abnormalities in distribution with direct retrograde coronary sinus cardioplegia are not affected by changes in the dosage or pressure of injection.     

Collateral back pressure—Is it a valid predictor of infrainguinal bypass graft patency?

While it is generally thought that collateral back pressure (CBP) is a reliable predictor of graft patency, this correlation has not yet been validated. We have used a new, simple technique to measure CBP without direct puncture of the recipient artery. After the distal anastomosis is completed, the graft is filled with saline and clamped proximally. A transducer connected needle is then inserted into the distal portion of the graft for CBP measurements (mm Hg). These were obtained in 84 grafts (43 femoropopliteals [FP] and 41 femorodistals [FD]). Outflow resistance (OR) measurements (mm Hg/ml/min) were also obtained in 70 (36 FP; 34 FD) of these grafts by a previously described technique. The mean CBP for FP and FD bypasses was 41 +/- 17 and 26 +/- 19 mm Hg, respectively (P less than 0.001). Although early graft patency (3 months) (13 occluded, 71 patent) did not correlate with angiographic findings of popliteal runoff or integrity of pedal arch, it did significantly relate to CBP. Mean CBP for occluded grafts was 22 +/- 17 mm Hg and for patent grafts it was 36 +/- 19 mm Hg (P less than 0.01). Similarly, mean OR was significantly related to patency, 1.29 +/- 0.23 mm Hg/ml/min for occluded grafts and 0.36 +/- 0.23 mm Hg/ml/min for patent grafts (P less than 0.0001). Moreover, only OR was a significant predictor of infrapopliteal graft patency (P less than 0.01). OR was found to be a better predictor of graft patency than CBP by stepwise logistic regression analysis (P less than 0.0001). We conclude that CBP is a more reliable predictor of graft outcome than angiographic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis.

This study investigates the role of prostaglandins (PG) in hyperdynamic sepsis. Thirteen chronically instrumented dogs were rendered septic by implanting in the peritoneal cavity a fibrin clot containing viable Escherichia coli. One day later, cardiac output (CO) increased from 2.80 +/- 0.22 to 3.72 +/- 0.32 l/min (p = 0.011); heart rate (HR) increased from 122 +/- 8 to 147 +/- 6 beats/min (p = 0.005); mean pulmonary artery pressure (PAP) increased from 15 +/- 1 to 19 +/- 1 mmHg (p = 0.003); mean systemic arterial pressure (MAP) decreased from 120 +/- 5 to 107 +/- 7 mmHg; and systemic vascular resistance (SVR) decreased from 44.1 +/- 2.6 to 29.3 +/- 1.9 mmHg/l/min (p less than 0.001). Sixty minutes after intravenous injection of indomethacin (2 mg/kg) or ibuprofen (25 mg/kg), CO decreased to 2.60 +/- 0.21 l/min (p less than 0.001); HR decreased to 118 +/- 5 beats/min (p less than 0.001); PAP decreased to 17 +/- 1 mmHg (p = 0.021); and SVR increased to 43.7 mmHg/l/min (p less than 0.001). In seven control dogs, laparotomy alone did not significantly affect any of these parameters. Infusion of indomethacin caused a slight increase in MAP (106 +/- 4 to 116 +/- 4 mmHg, p = 0.035) but otherwise did not alter hemodynamics. It is concluded that administration of indomethacin or ibuprofen restores normal hemodynamics in a canine model of high-output sepsis, probably by inhibiting PG synthesis.     

Modified polytetrafluoroethylene: indium 111-labeled platelet deposition on carbon-lined and high-porosity polytetrafluoroethylene grafts.

Platelet accumulation on carbon-lined (CL) and high-porosity (HP) polytetrafluoroethylene (PTFE) grafts was investigated in vivo. In experiment 1, 20 CL grafts and 20 control PTFE grafts, each 5 cm in length and 4 mm in diameter, were interposed into both carotid and femoral arteries of 10 dogs. In experiment 2, 12 HP grafts (90 microns mean internodal distance) and 12 control PTFE grafts were implanted in six dogs. Indium 111-labeled platelets were injected intravenously and the grafts were retrieved 48 hours later. Radioactivity of the grafts and a control segment of the carotid artery was counted. A graft platelet accumulation index (GPAI) was calculated as the ratio of emission from the graft compared to that from the control segment. The GPAI of the CL graft was significantly less than the GPAI of the control graft in both the carotid (control 29.7 +/- 5.46, CL 22.3 +/- 6.55; n = 9 [p < 0.05]) and the femoral arteries (control 30.7 +/- 9.65, CL 22.0 +/- 6.59; n = 9 [p < 0.05]). There was no significant difference in GPAI between the control and HP grafts in the carotid arteries (control 30.6 +/- 11.8, HP 31.5 +/- 9.71; n = 6) and in the femoral arteries (control 31.5 +/- 7.88, HP 34.0 +/- 4.97; n = 6). Carbon lining decreases platelet accumulation on PTFE grafts in the early postoperative period, and HP grafts do not exhibit increased platelet uptake.     

Effect of preclotting and precoating agents on seeded venous grafts

This study evaluated the effect of whole blood preclotting (WB), fibronectin (FB) and "Cell Tak" (CT) precoating on the patency rate of seeded vena cava grafts. Ten cm x 8 mm ID ringed PTFE grafts were implanted in the vena-cavae of 29 dogs. Aspirin (325 mg po qd) was administered pre-operatively and continued post-operatively. After preclotting or precoating, all grafts were seeded with porcine endothelial cells. The 32 day patency rates were: 67%, 67% and 37% for WB, FB and CT, respectively (p less than 0.5 CT vs FB, WB). Endothelialized surfaces ranged from 67 +/- 35, 43 +/- 41 to 28 +/- 45% respectively for WB, FB and CT (p less than 0.05 CT vs WB). Preclotting time was shortest for WB technique. We conclude that: 1) FB and WB grafts have the highest patency rate with WB preclotting being a more cost effective and less time consuming technique; 2) endothelial seeding and Aspirin may make vena cava grafting possible.     

Six-year prospective multicenter randomized comparison of autologous saphenous vein and expanded polytetrafluoroethylene grafts in infrainguinal arterial reconstructions

Autologous saphenous vein (ASV) and polytetrafluoroethylene (PTFE) grafts were compared in 845 infrainguinal bypass operations, 485 to the popliteal artery and 360 to infrapopliteal arteries. Life-table primary patency rates for randomized PTFE grafts to the popliteal artery paralleled those for randomized ASV grafts to the same level for 2 years and then became significantly different (4-year patency rate of 68% +/- 8% [SE] for ASV vs. 47% +/- 9% for PTFE, p less than 0.025). Four-year patency differences for randomized above-knee grafts were not statistically significant (61% +/- 12% for ASV vs. 38% +/- 13% for PTFE, p greater than 0.25) but were for randomized below-knee grafts (76% +/- 9% for ASV vs. 54% +/- 11% for PTFE, p less than 0.05). Four-year limb salvage rates after bypasses to the popliteal artery to control critical ischemia did not differ for the two types of randomized grafts (75% +/- 10% for ASV vs. 70% +/- 10% for PTFE, p greater than 0.25). Although primary patency rates for randomized and obligatory PTFE grafts to the popliteal artery were significantly different (p less than 0.025), 4-year limb salvage rates were not (70% +/- 10% vs. 68% +/- 20%, p greater than 0.25). Primary patency rates at 4 years for infrapopliteal bypasses with randomized ASV were significantly better than those with randomized PTFE (49% +/- 10% vs. 12% +/- 7%, p less than 0.001). Limb salvage rates at 3 1/2 years for infrapopliteal bypasses with both randomized grafts (57% +/- 10% for ASV and 61% +/- 10% for PTFE) were better than those for obligatory infrapopliteal PTFE grafts (38% +/- 11%, p less than 0.01). These results fail to support the routine preferential use of PTFE grafts for either femoropopliteal or more distal bypasses. However, this graft may be used preferentially in selected poor-risk patients for femoropopliteal bypasses, particularly those that do not cross the knee. Although every effort should be made to use ASV for infrapopliteal bypasses, a PTFE distal bypass is a better option than a primary major amputation.     

Comparison of the action kinetics of alcuronium and vecuronium by electromyographic monitoring

Twenty-eight ASA I or ASA II adults undergoing microsurgery were anaesthetized according to a standard protocol using droperidol, phenoperidine and thiopentone followed by enflurane. The patients were randomly assigned to two homogeneous groups: the first group (n = 14) received 0.2 mg.kg-1 alcuronium, whereas the second group (n = 14) received 0.08 mg.kg-1 vecuronium. There was no reinjection of either drug and curarization tapered off spontaneously. Neuromuscular monitoring was begun once anaesthesia was stable and after intentional isovolaemic haemodilution. The type of stimulus used was the train-of-four, delivered by a Relaxograph monitor to the ulnar nerve. Muscle response was measured at the hypothenar eminence. The kinetic study considered the time interval required between the injection of the muscle relaxant and the appearance of the minimal value of the twitch (first response of the train-of-four = T1min). The times to recovery of the twitch height to 25, 75 and 100% of the reference value (T1/T0) and of the fourth response of the train-of-four to 25 and 75% of the ratio (T4/T1) were also recorded. Finally, the recovery indexes represented by the times required for T1/T0 and T4/T1 to rise from 25% to 75% respectively were studied. The maximal twitch height inhibition was significantly greater (p less than 0.001) in the vecuronium group (T1min = 0.36 +/- 1.33%) than in the alcuronium group (T1min = 4.36 +/- 5.08%); it occurred significantly more quickly (p less than 0.001) with vecuronium (139 +/- 48 s) than with alcuronium (316 +/- 133 s).(ABSTRACT TRUNCATED AT 250 WORDS)     

Patency in canine inferior vena cava grafting: effects of graft material, size, and endothelial seeding

We studied 117 inferior vena cava (IVC) replacements in dogs to determine the effects of graft material, graft size, endothelial seeding, and cultured endothelial linings on graft patency. As a control, the IVC was removed and reimplanted in 11 dogs. Dacron (n = 7) and expanded polytetrafluoroethylene (e-PTFE) grafts (n = 12) were seeded immediately with the use of enzymatically derived autogenous jugular vein endothelium. Cultured linings were prepared for e-PTFE grafts (n = 9) by inoculating the graft with jugular endothelium and nurturing the lining in tissue culture for 14 to 30 days before implantation. Unseeded grafts (n = 27) were prepared according to the manufacturer's recommendations. These six methods of preparation were tested in grafts measuring 6 mm I.D. and 60 mm in length. Other sizes were tested with a Latin square study design. After 30 to 60 days the grafts were perfusion fixed and studied with light and transmission electron microscopy. Patency was determined by contrast cavography after 7 and 30 days. Patency in the IVC reimplantation was 100% compared with 28.0% of the e-PTFE (p = 0.001) and none of the Dacron grafts that measured 6 mm I.D. and 60 mm long. e-PTFE and Dacron graft patency also differed significantly (p = 0.035). Seeded and culture-lined e-PTFE grafts in that same size were patent in 31.6% compared with 16.7% of unseeded e-PTFE. With grafts measuring 80 mm long, three of the five e-PTFE grafts were patent between 3 and 7 days. All progressed to occlusion by 30 days and compared poorly with all other graft sizes tested (2.6% progression to occlusion [p = 3 X 10(-8)]). Recanalization was not seen in 10 occluded grafts that were followed for 60 days. The histologic features of seeded grafts differed remarkably from grafts previously studied in the arterial circulation and from culture-lined and unseeded venous prostheses in that 60% had prominent large, random, endothelium-lined channels within the inner capsule. Larger graft diameters (p = 0.009) and the omission of an endothelial surface treatment (p = 0.004) were associated with anastomotic subendothelial fibrous hyperplasia. We conclude that graft material is the major determinant of patency in IVC replacements, that an extensive endothelial surface promotes patency, but that simply seeding e-PTFE or Dacron grafts with 10(5) endothelial cells does not provide sufficient endothelium to alter early patency.(ABSTRACT TRUNCATED AT 400 WORDS)     

PTFE or HUV for femoro-popliteal bypass: a multi-centre trial

Despite wide clinical experience the choice between human umbilical vein (HUV) or polytetrafluoroethylene (PTFE) when the saphenous vein is inadequate remains unclear. In a multi-centre trial of 801 femoro-popliteal bypasses, autogenous vein could not be used in 252 (31%), of which 191 were randomised to either HUV or PTFE and started on aspirin 300 mg plus dipyridamole 150 mg (ASA + DPM) twice daily. Graft patency measured objectively by independent trial coordinators was expressed on an "intention to treat" basis by life table and analysed statistically by log rank and confidence intervals (95% CI). Overall, 101 grafts failed and cumulative patency was 53% (45-61%) at 3 years compared with 60% (55-65%) in 549 vein grafts. Prosthetic bypass patency above knee was 65% (55-75%); markedly better than 35% (23-47%) below knee (p less than 0.001) and comparable with 62% (55-69%) in 217 above knee saphenous vein grafts. Most failures occurred early at a rate of 52/1000 patient-months in the first 3 months (43/1000 for vein) falling to 21/1000 by 6 to 12 months and around 10/1000 subsequently. Randomisation produced comparable groups of 87 HUV and 104 PTFE grafts. Cumulative primary patency for HUV was 68, 63 and 57% at 1, 2 and 3 years, respectively compared with 61, 56 and 48% for PTFE with wide confidence intervals for the difference at 3 years (-20 to 38%, p = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vein cuff interposition prevents juxta-anastomotic neointimal hyperplasia.

This study sought to minimize juxta-anastomotic neointimal hyperplasia (JNIH) following the use of polytetrafluorethylene (PTFE) conduits. PTFE anastomoses to canine carotid arteries (noncuff grafts) were compared with grafts with vein cuffs interposed proximally and distally between the graft and native artery. This technique has been suggested clinically for below-knee PTFE femoropopliteal reconstruction. Twelve dogs received aspirin for 1 week before operation, which was continued after each animal received bilateral cuff and noncuff 4-mm PTFE grafts. At sacrifice, after 3-12 weeks, graft patency was assessed and luminal diameters measured with ophthalmic calipers at three sites along the anastomoses and 1 mm proximal or distal to graft toe (A' diameter). Specimens were perfusion fixed at arterial pressure for gross and histologic study; selected arteries were additionally fixed with 4% buffered glutaraldehyde, stored at 4 C, and examined immunochemically using antimyosin antibody immunopurified for smooth muscle. Overall patency of noncuff grafts in 11 long-term surviving dogs was 4 of 11; patency of the cuff grafts was 7 of 11. Regardless of graft thrombosis, antibody positive cellular proliferation occurred mainly at noncuffed PTFE anastomoses. Luminal encroachment was predominantly due to subintimal proliferation of cells highly reactive to smooth muscle derived antibody. JNIH was most prominent 1 mm distal to the graft toe (A' distal diameter). Average A' for noncuff grafts was 1.82 mm +/- 0.97 SEM; average A' diameter for cuff grafts was 3.41 mm +/- 0.74 SEM (p less than 0.001). Vein cuff inhibition of proliferation of smooth muscle or cells derived from smooth muscle possibly relates to wider distribution of kinetic energy (less compliance mismatch) or to interposition of venous endothelium.     

Transplantation of purified single-donor canine islet allografts with cyclosporine

We evaluated the survival of highly purified freshly isolated pancreatic islets transplanted from single canine donors into 20 outbred mongrel dogs immunosuppressed with cyclosporine or untreated. The grafts (mean weight +/- SE, 0.5 +/- 0.1 g, containing 122 +/- 8 X 10(3) islets; purity 91% by electron microscopy) were transplanted into 3 groups of dogs: group 1, autograft without CsA (5444 +/- 688 islets/kg body weight, n = 6); group 2, allograft without CsA (6669 +/- 1744, n = 4); and group 3, allograft with CsA (8645 +/- 1149, n = 10). The CsA was injected i.m. daily for 4 days before and 30 days after transplantation. Fasting plasma glucose (PG, mg/dl) and serum CsA trough values were determined daily. Intravenous glucose tolerance tests were done before and after transplantation, for calculation of K values (decline in glucose, %/min; preoperatively, mean K = 3.9 +/- 0.2). In group 1 all 6 dogs were normoglycemic (PG = 98 +/- 2 and K = 1.8 +/- 0.2) at 1 month; in group 2 the graft failed in all 4 dogs, at 4 +/- 1.2 days; in group 3 all 10 dogs were normoglycemic initially. Of the group 3 dogs, 4 died (intussusception developed in 2, and the graft failed at 3 and 9 days in 2 the CsA values of which were less than 300 micrograms/L preoperatively), but the other 6 were still normoglycemic when the CsA was stopped at 30 days (mean PG = 132 +/- 16 and K = 0.9 +/- 0.2; P less than 0.05 vs. group 1). Their CsA values were 708 +/- 197 before and 359 +/- 41 micrograms/L during the third week after transplantation; their grafts failed 12.3 +/- 3.4 days after the cessation of CsA. This data is unique in demonstrating prolonged function of purified allogeneic islets transplanted from individual outbred canine donors, but glucose tolerance was impaired. CsA at serum levels greater than 300 micrograms/L induced prolonged survival of purified canine islets and rejection was prompt when it was stopped.