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Treatment of prosthetic graft infections
Grafts, Clips and New Methods Forearm Clips
1 prosthetic 16 autologous Sutures 2 prosthetic 15 autologous
Antecubital Upperarm 4 prosthetic 14 autologous 6 prosthetic 10 autologous
Thigh
3 prosthetic 2 prosthetic 2 autologous 1 prosthetic 2 prosthetic 3 autologous
Pre-operative, operative, and post-operative comparisons and evaluations include: patient risk factors and vascular status, intraoperative efficiency, anastomotic construction times, anastomotic bleeding grading, together with progression to maturation for dialysis, fistula patency, adverse effects, dialytic parameter changes over time, and radiographic appearances of the anastomotic sites 6 months after surgery. Fiftytwo patients are currently on dialysis. Angiographic and flow Doppler studies are being conducted at 6 months. The clip has proven at least equivalent to conventional needle-and-suture for construction of vascular access sites, the learning curve for its application is rapid, and with experience, time for anastomosis construction is effectively reduced. 26.7 FGF-1 Impregnation of EPTFE G r a f t s - Release Kinetics and Tissue Distribution M.K. HIRKO, P.H. LIN, C. GOSSELIN, D. REN and H.P. GREISLER, Maywood, lllinois, USA The regulation of smooth muscle cell (SMC) and endothelial cell (EC) proliferation subsequent to vascular interventions is crucial to clinical efficacy, especially long-term patency of small-diameter vascular prostheses. We have reported a method of impregnating ePTFE grafts with fibrin glue fiG), FGF-I, and heparin, and have shown enhanced endothelial proliferation with concurrent SMC growth inhibition in vitro using a 10 ng FGF-I: 250 U heparin ratio. The present study characterizes a) in vivo tissue distribution of an intra-arterially slowly delivered a251-FGF-1:heparin solution, and b) in vivo release kinetics of 12SI-FGF-1 from ePTFE impregnated with FG containing FGF-1 and either of two different heparin concentrations, since our newer in vitro data have suggested that increasing the heparin dose to 200 U/ml from 33 U/ml may further suppress neointimal hyperplasia. METHODS: a) ~2SI-FGF-1 and heparin were infused proximally into the ligated left carotid artery for 24 h in four New Zealand White (NZW) rabbits using an Alzet osmotically activated pumping device (#2001D). The total delivered dosage (1.1 ng f25 I-FGF1 and 28 U heparin) was that which we previously reported from arterially implanted FGF-1/heparin impregnated ePTFE grafts. Rabbits were sacrificed at 24 h, exsanguinated, and biopsies removed from all internal organs. These samples were assayed for radioactivity and results expressed as cpm 12Sl/g wet weight tissue. Similar calculations were also measured after the samples were dried in an oven at 100°F for 24 h; b) FGF-1/FG suspensions containing 10 ng/m112SI-FGF-1, 32 mg/ml fibrinogen, 0.32 U/ml thrombin, and heparin at either 33 U/ml or 200 U/ml were pressure perfused into 24 m m × 4 mm ePTFE grafts (lmpra, Inc., Tempe, AZ). Grafts had an average internodal distance of 60 p.m, wall thickness of 0.7 mm, and no external support wrap. Grafts were interposed into infrarenal aortas of 48 NZW rabbits (n = 24/heparin group) and were explanted in triplicates after 0, 5, 30. and 60 min and 1, 7, 14, and 30 days. Release kinetics of lzfI-FGF-I
CARDIOVASCULAR SURGERY SEPTEMBER 1995
was determined by the residual activity of the explanted specimens at any time point divided by the calculated residual activity for that prostheses at time 0. RESULTS: a) lzsI-FGF-1 uptake (cpm/g dry wt.) was greatest in the thyroid (551.1 + 131.4). This was significantly greater (P <0.05) than those organs with intermediatc uptake (lungs, liver, kidneys, spleen, and heart), and differed significantly (P <0.05) from those with lowest uptake (blood, muscle, and fat). 12SI-FGF-1 specific activity (cpm/g tissue x total dry wt. tissue) was greatest in the liver (818.1 +_ 176.3 cpm). This was 4-20-times greater than other 'filter' organs (kidneys, lungs, and spleen). Lowest specific activity was noted in the spleen (43.25 ± 3.09) and thyroid (66.00 ± 16.51). b) Grafts treated with 12SI-FGF-1, FG, and either 33 U/ml or 200 U/mi heparin showed a loss at time 0 of 20.7 ± 9.5% and 36.3 ± 17% (P = 0.24) respectively as a result of surgical manipulation alone. Both groups showed a relatively rapid initial loss of radiolabel in the first 5 rain of circulation, declining substantially after the first 60 min. After 7 days of circulation, grafts treated with 33 U/ml and 200 U/ml heparin showed a retention rate of 13.0 ___ 7% and 5.4 +_ 0.2% respectively (P = 0.13); also, no statistically significant differences were noted at 30 days (P = 0.11) between these two groups. The current results show that varying the concentration of heparin within FGF-1/FG does not significantly (P = 0. 1) alter the release kinetics of lzsI-FGF-1 in circulation. While no FGF-l-induced toxicity was noted in the tissue distribution portion of this study, these results will allow for future tissue-specific toxicology studies prior to clinical trials. 26.8
Prospective Randomized Trial of PTFE and Gelatinsealed Dacron for Femoropopliteal, Femorofemoral and Axillofemoral Bypass [.P. FLETCHER and B. ROBINSON, Sydney, Australia Animal studies have shown rifampicin-bonded gelatin sealed Dacron (Gelsoft) to be an effective infection-resistant vascular graft, but with a higher incidence of initimal hyperplasia and graft occlusion than polytetrafluoroethylene (PTFE). This animal work has been extended to a clinical trial comparing Gelsoft with PTFE with and without rifampicin. Patients having femoro-femoral, axillo-femoral and femoro-popliteal bypass with prosthetic vascular graft were randomized to receive either PTFE or Gelsoft with or without rifampicin soaking of the vascular graft prior to insertion. There have been 108 patients entered into the study up to 31st August 1994, 78 of whom received a femoro-popliteal bypass. Patency rate overall has been 92% at 1 month and 74% at 1 year (94% and 74% respectively for the femoro-popliteal bypass group). There has been no difference in patency between Gelsoft and PTFE or between grafts with and without rifampicin soaking. The incidence of infective complications has been low with no difference to date between grafts treated or not treated with rifampicin. 26.9
Treatment of Prosthetic Graft Infections G. BIRO, L. ENTZ, L. PINTER and A. NEMES, Budapest, Hungary This paper will be presented at the meeting.
137
1 prosthetic 16 autologous Sutures 2 prosthetic 15 autologous
Antecubital Upperarm 4 prosthetic 14 autologous 6 prosthetic 10 autologous
Thigh
3 prosthetic 2 prosthetic 2 autologous 1 prosthetic 2 prosthetic 3 autologous
Pre-operative, operative, and post-operative comparisons and evaluations include: patient risk factors and vascular status, intraoperative efficiency, anastomotic construction times, anastomotic bleeding grading, together with progression to maturation for dialysis, fistula patency, adverse effects, dialytic parameter changes over time, and radiographic appearances of the anastomotic sites 6 months after surgery. Fiftytwo patients are currently on dialysis. Angiographic and flow Doppler studies are being conducted at 6 months. The clip has proven at least equivalent to conventional needle-and-suture for construction of vascular access sites, the learning curve for its application is rapid, and with experience, time for anastomosis construction is effectively reduced. 26.7 FGF-1 Impregnation of EPTFE G r a f t s - Release Kinetics and Tissue Distribution M.K. HIRKO, P.H. LIN, C. GOSSELIN, D. REN and H.P. GREISLER, Maywood, lllinois, USA The regulation of smooth muscle cell (SMC) and endothelial cell (EC) proliferation subsequent to vascular interventions is crucial to clinical efficacy, especially long-term patency of small-diameter vascular prostheses. We have reported a method of impregnating ePTFE grafts with fibrin glue fiG), FGF-I, and heparin, and have shown enhanced endothelial proliferation with concurrent SMC growth inhibition in vitro using a 10 ng FGF-I: 250 U heparin ratio. The present study characterizes a) in vivo tissue distribution of an intra-arterially slowly delivered a251-FGF-1:heparin solution, and b) in vivo release kinetics of 12SI-FGF-1 from ePTFE impregnated with FG containing FGF-1 and either of two different heparin concentrations, since our newer in vitro data have suggested that increasing the heparin dose to 200 U/ml from 33 U/ml may further suppress neointimal hyperplasia. METHODS: a) ~2SI-FGF-1 and heparin were infused proximally into the ligated left carotid artery for 24 h in four New Zealand White (NZW) rabbits using an Alzet osmotically activated pumping device (#2001D). The total delivered dosage (1.1 ng f25 I-FGF1 and 28 U heparin) was that which we previously reported from arterially implanted FGF-1/heparin impregnated ePTFE grafts. Rabbits were sacrificed at 24 h, exsanguinated, and biopsies removed from all internal organs. These samples were assayed for radioactivity and results expressed as cpm 12Sl/g wet weight tissue. Similar calculations were also measured after the samples were dried in an oven at 100°F for 24 h; b) FGF-1/FG suspensions containing 10 ng/m112SI-FGF-1, 32 mg/ml fibrinogen, 0.32 U/ml thrombin, and heparin at either 33 U/ml or 200 U/ml were pressure perfused into 24 m m × 4 mm ePTFE grafts (lmpra, Inc., Tempe, AZ). Grafts had an average internodal distance of 60 p.m, wall thickness of 0.7 mm, and no external support wrap. Grafts were interposed into infrarenal aortas of 48 NZW rabbits (n = 24/heparin group) and were explanted in triplicates after 0, 5, 30. and 60 min and 1, 7, 14, and 30 days. Release kinetics of lzfI-FGF-I
CARDIOVASCULAR SURGERY SEPTEMBER 1995
was determined by the residual activity of the explanted specimens at any time point divided by the calculated residual activity for that prostheses at time 0. RESULTS: a) lzsI-FGF-1 uptake (cpm/g dry wt.) was greatest in the thyroid (551.1 + 131.4). This was significantly greater (P <0.05) than those organs with intermediatc uptake (lungs, liver, kidneys, spleen, and heart), and differed significantly (P <0.05) from those with lowest uptake (blood, muscle, and fat). 12SI-FGF-1 specific activity (cpm/g tissue x total dry wt. tissue) was greatest in the liver (818.1 +_ 176.3 cpm). This was 4-20-times greater than other 'filter' organs (kidneys, lungs, and spleen). Lowest specific activity was noted in the spleen (43.25 ± 3.09) and thyroid (66.00 ± 16.51). b) Grafts treated with 12SI-FGF-1, FG, and either 33 U/ml or 200 U/mi heparin showed a loss at time 0 of 20.7 ± 9.5% and 36.3 ± 17% (P = 0.24) respectively as a result of surgical manipulation alone. Both groups showed a relatively rapid initial loss of radiolabel in the first 5 rain of circulation, declining substantially after the first 60 min. After 7 days of circulation, grafts treated with 33 U/ml and 200 U/ml heparin showed a retention rate of 13.0 ___ 7% and 5.4 +_ 0.2% respectively (P = 0.13); also, no statistically significant differences were noted at 30 days (P = 0.11) between these two groups. The current results show that varying the concentration of heparin within FGF-1/FG does not significantly (P = 0. 1) alter the release kinetics of lzsI-FGF-1 in circulation. While no FGF-l-induced toxicity was noted in the tissue distribution portion of this study, these results will allow for future tissue-specific toxicology studies prior to clinical trials. 26.8
Prospective Randomized Trial of PTFE and Gelatinsealed Dacron for Femoropopliteal, Femorofemoral and Axillofemoral Bypass [.P. FLETCHER and B. ROBINSON, Sydney, Australia Animal studies have shown rifampicin-bonded gelatin sealed Dacron (Gelsoft) to be an effective infection-resistant vascular graft, but with a higher incidence of initimal hyperplasia and graft occlusion than polytetrafluoroethylene (PTFE). This animal work has been extended to a clinical trial comparing Gelsoft with PTFE with and without rifampicin. Patients having femoro-femoral, axillo-femoral and femoro-popliteal bypass with prosthetic vascular graft were randomized to receive either PTFE or Gelsoft with or without rifampicin soaking of the vascular graft prior to insertion. There have been 108 patients entered into the study up to 31st August 1994, 78 of whom received a femoro-popliteal bypass. Patency rate overall has been 92% at 1 month and 74% at 1 year (94% and 74% respectively for the femoro-popliteal bypass group). There has been no difference in patency between Gelsoft and PTFE or between grafts with and without rifampicin soaking. The incidence of infective complications has been low with no difference to date between grafts treated or not treated with rifampicin. 26.9
Treatment of Prosthetic Graft Infections G. BIRO, L. ENTZ, L. PINTER and A. NEMES, Budapest, Hungary This paper will be presented at the meeting.
137