Biomedical subjects
M S Conte
Publications and source records attributed to M S Conte.
Targeting platelet aggregation: CD39 gene transfer augments nucleoside triphosphate diphosphohydrolase activity in injured rabbit arteries.
BACKGROUND: CD39, the major endothelial nucleoside triphosphate diphosphohydrolase (NTPDase), plays an important role in local thromboregulation. We hypothesized that balloon injury (BI) leads to an acute reduction in arterial NTPDase activity that could be restored by a targeted gene delivery strategy. METHODS: Recombinant adenoviral vectors containing human CD39 (Ad-CD39) or beta-galactosidase (Ad-LacZ) were used. Endothelial (ECs) and smooth muscle cells (SMCs) were infected in vitro and NTPDase activity measured. New Zealand white rabbits (N = 28) underwent bilateral iliofemoral artery balloon injury, followed by incubation with Ad-CD39, Ad-LacZ, or vehicle. Explanted vessels were analyzed for NTPDase activity and localization of CD39 expression by immunohistochemistry. Deposition of fluorescent-labeled platelets was studied 3 days after injury and vector treatment. RESULTS: In vitro, Ad-CD39 infection resulted in a greater than 40-fold increase in adenosine diphosphatase activity in ECs and a 3-fold increase in SMCs. In vivo, CD39 transgene expression localized to the luminal aspect of Ad-CD39--treated vessels. BI resulted in an acute reduction in vessel wall NTPDase activity (P <.05). Ad-CD39 augmented NTPDase activity when compared with vehicle or Ad-LacZ (P <.05). Platelet deposition on the injured arterial surface was modest and not different between Ad-CD39-- and Ad-LacZ--treated vessels. CONCLUSIONS: BI decreases native NTPDase activity, which can be augmented by adenovirus-mediated gene transfer of CD39. Further studies are required to determine whether targeted delivery of CD39 could convey thromboprotective properties to an injured vessel.
Autogenous composite vein bypass graft for infrainguinal arterial reconstruction.
PURPOSE: Lower extremity arterial reconstruction in the absence of adequate greater saphenous vein remains a challenging problem in contemporary vascular practice. The purpose of this review is to evaluate the long-term results of autogenous composite vein grafts used for infrainguinal arterial bypass grafting. METHODS: We retrospectively evaluated a prospective vascular registry and reviewed inpatient and office records. RESULTS: From June 1983 to September 1999, 165 autogenous composite vein infrainguinal bypass grafts were performed in 154 patients (87 men, 67 women; mean age, 69 years). The mean follow-up was 25 months (range, 3-147). Patients had the usual risk factors, including a 30% incidence of prior coronary bypass grafting. Forty-eight percent of bypass grafts were performed after failed previous reconstructions, and 90% were performed for limb salvage. The conduits were comprised of 2 segments (75%), 3 segments (23%), and 4 segments (2%). The distal anastomosis was at the popliteal level in 17% and the tibial/pedal level in 83%. The 30-day operative mortality rate was 1.8%. Perioperative graft failure (< 30 days) occurred in 18 bypass grafts (11%), resulting in early amputation (< 30 days) in 1.2%. The overall 5-year cumulative patency rates were 44% +/- 5% for primary patency, 63% +/- 5% for primary-assisted patency (PAP), and 65% +/- 5% for secondary patency (SP). A high revision rate for stenosis or thrombosis was required during follow-up to maintain patency of the grafts (27%). Limb salvage was 81% +/- 5% at 5 years. Primary reconstructions with composite vein fared significantly better than secondary reconstructions (SP 76% vs 54% at 5 years, P <.01). Arm vein composites showed superior patency compared with greater saphenous vein composites (SP 79% vs 61% at 5 years, P <.05). CONCLUSIONS: Infrainguinal reconstruction with autogenous composite vein results in durable graft patency and limb salvage rates in patients with few alternatives for revascularization. Intensive graft surveillance with aggressive graft revision is necessary to achieve these results.
Monocyte adhesion to balloon-injured arteries: the influence of endothelial cell seeding.
OBJECTIVE: Deendothelialization of injuries of the artery disrupts normal vascular homeostasis, affecting both the structural integrity of the blood vessel wall, as well as the interaction of the arterial surface with blood components such as platelets, leukocytes, and circulating proteins. Leukocyte and, in particular, monocyte recruitment to damaged vessels has been implicated in the pathogenesis of intimal hyperplasia. We hypothesize that reendothelialization is an important modulator of monocyte adhesion to healing arterial surfaces. METHODS: New Zealand white rabbits (n = 20) were subjected to bilateral iliofemoral artery balloon injury. Cultured, autologous venous endothelial cells (ECs) were immediately seeded onto one vessel, whereas the contralateral artery received medium alone, to accelerate endothelial relining. Vessels were harvested (5-9 days after injury) for analysis of permeability (Evans Blue dye exclusion), endothelial coverage (anti-CD31 immunohistochemistry), monocyte adhesion (ex vivo binding of 51Na2CrO4-labeled monocytic THP-1 cells), and monocyte recruitment (RAM-11 immunohistochemistry). RESULTS: Improved EC coverage was evidenced by positive staining for CD31 in the seeded vessels. Vessel wall permeability was markedly reduced in EC-seeded arteries (29% +/- 10% vs 99% +/- 0% surface Evans blue staining, P <.005), consistent with restoration of a functional endothelial barrier. EC seeding significantly reduced ex vivo THP-1 binding to vessels explanted at a mean of 8 days after injury (45,170 +/- 8939 vs 85,994 +/- 16,500 cells/cm2, P <.05). However, RAM-11 staining revealed no significant difference in overall macrophage accumulation between seeded and control vessels 1 week after injury (111 +/- 22 vs 95 +/- 14 cells/section, P =.36). CONCLUSIONS: Immediate seeding of a balloon-injured rabbit artery with cultured ECs results in accelerated restoration of the endothelial lining. At 1 week, barrier function is improved, and the seeded vessel surface is less adhesive to activated monocytes ex vivo, as compared with injured controls. Nonetheless, EC-seeded and nonseeded arteries demonstrate similar total macrophage accumulation over 1 week. These data suggest that after mechanical arterial injury, endothelial coverage may be one important variable influencing leukocyte adhesion.
Infrainguinal bypass grafting in patients with end-stage renal disease: improving outcomes?
OBJECTIVE: This study was undertaken to examine recent trends in the outcomes of patients with end-stage renal disease (ESRD) undergoing infrainguinal bypass grafting (IBG) with autogenous vein. METHODS: A retrospective analysis of all IBGs performed on patients with ESRD at a single tertiary care institution during the interval 1993 to 1999 was undertaken. The comparison groups consisted of concurrent series of patients with elevated creatinine (creatinine level > 1.2 mg/dL) and patients with normal renal function undergoing IBG. Procedural variables, angiographic runoff scores, and extent of tissue necrosis at presentation were correlated with outcome. Categoric parameters were compared with chi(2) analysis; rates were computed with life-table analysis. RESULTS: Of an overall cohort of 622 IBGs performed during this interval, 78 IBGs (12.5%) were performed on 60 patients with ESRD, with a perioperative mortality rate of 1.3% that was comparable to controls. All reconstructions in the ESRD cohort were for limb salvage indications. Four-year survival, primary, assisted primary, and secondary patency rates for the ESRD group were 51% +/- 9%, 60% +/- 11%, 86% +/- 5%, and 86% +/- 5%, respectively; these were not statistically different from the control groups. Limb salvage in the ESRD group was 77% +/- 6% at 4 years and was significantly less then either the elevated creatinine (92% +/- 4%; P <.02) or the normal renal function group (90% +/- 2%: P <.02). Of 16 amputations in the ESRD group, nine were performed in limbs with patent grafts. The only absolute predictor of limb loss despite a patent graft was the presence of a heel ulcer more than 4 cm in diameter. Age, runoff score of the International Society for Cardiovascular Surgery/Society for Vascular Surgery, isolated tibial bypass graft, and location of distal anastomosis were not predictive of hemodynamic failure. CONCLUSIONS: Patients with ESRD constitute an increasing proportion of patients undergoing IBG in a tertiary care setting. Four-year survival, perioperative mortality, and graft patency rates are similar to patients with normal renal function and support an aggressive approach to this population. Major limb amputation despite a patent graft remains a problem of unique frequency in patients with ESRD. Adequate predictors of hemodynamic failure of IBG in this group do not exist, although a heel ulcer more than 4 cm may indicate an unsalvageable foot.
Monocyte adhesion to human vein grafts: a marker for occult intraoperative injury?
OBJECTIVE: Monocyte adhesion to the vessel wall is believed to be an important initiating event in atherosclerosis and intimal hyperplasia. We hypothesized that occult intraoperative vein injury induces an immediate increase in monocyte adhesion that may be critical to the development of vein graft disease. METHODS: Vein segments were obtained from patients (n = 23) undergoing lower extremity bypass. The initial segment (V1, n = 17) was excised immediately at the time of conduit harvest. A second segment (V2, n = 23) was obtained from the distal conduit just before performing the distal anastomosis. Segments were incubated with radiolabeled THP-1 cells (monocytoid cell line) for 1 hour at 37 degrees C, then rinsed and solubilized for determination of bound radioactivity. In a subset of grafts (n = 4), THP-1 cells were preincubated with monoclonal antibody (mAB) 7E3 (which binds to the monocyte integrin Mac-1 at its fibrinogen [Fg]-binding site) or control (mAB 14E11). Fg deposition and endothelial coverage were evaluated by immunohistochemistry (n = 10). Statistical analysis was performed using the paired t test and analysis of variance. Follow-up graft patency data were obtained and correlated with adhesion values using an exact test (StatXact, Cytel Software, Cambridge, Mass). RESULTS: Monocyte adhesion was significantly increased after surgical manipulation (V1, 2400 +/- 770 versus V2, 7343 +/- 1555 cells/cm(2); P <.02). Fg deposition was abundant in V2 sections and not seen in V1. Monocyte adhesion to V2 segments was significantly reduced (58% of control, P <.01) by 7E3 treatment. Graft follow-up was complete with a mean interval of 11 months. Higher V2 adhesion values were associated with occluded grafts (P =.07). The median value for the six occluded grafts was 6234 cells/cm(2) versus 3892 cells/cm(2) for the 17 patent grafts. CONCLUSIONS: Monocyte adhesion to the vein wall is immediately increased after surgical manipulation and is inhibited by mAB 7E3. Early monocyte adhesion to vein grafts is likely to involve interactions between Mac-1 and Fg. Heightened levels of monocyte adhesion at implantation may be a marker for subsequent vein graft failure.
Impact of increasing comorbidity on infrainguinal reconstruction: a 20-year perspective.
OBJECTIVE: To examine trends in patient and procedural variables and outcomes associated with autogenous lower extremity arterial reconstruction (LER) in a single center during a period of two decades. SUMMARY BACKGROUND DATA: Surgical arterial reconstruction is of proven value in the therapy of patients with critical ischemia of the lower extremities. Changing demographics and increasing comorbidity are resulting in an increasing prevalence and associated complexity of peripheral vascular disease. The effect of these variables on the types and outcomes of surgical reconstructions is not known. METHODS: The authors performed a retrospective analysis of all autogenous LER procedures performed at their institution from 1978 to 1997. Procedures were divided into 5-year intervals: group 1, 1978 to 1982; group 2, 1983 to 1987; group 3, 1988 to 1992; group 4, 1993 to 1997. Categorical parameters were compared using chi-square analysis; rates were computed by the life-table method and compared using Mantel-Cox log-rank analysis. RESULTS: A total of 1,642 autogenous LER procedures were performed in 1,274 patients. A significant increase in age, female gender, diabetes mellitus, renal failure, and prior coronary artery bypass grafting was noted in group 4. Increased technical complexity in this group was reflected by a greater incidence of tissue necrosis as the indication for LER, the use of ectopic or composite vein, and more distal levels of outflow. The surgical death rate remained unchanged (2%) throughout. Patient survival, primary and secondary graft patency, and limb salvage at 5 years for the entire cohort were 70 +/- 2%, 63 +/- 2%, 73 +/- 1%, and 85 +/- 1%, respectively. Hospital length of stay was reduced 25% from a mean of 15.7 +/- 0.8 days in group 3 to 11.7 +/- 0.4 days in group 4. CONCLUSION: In a tertiary practice setting, patients requiring LER present an increasingly complex medical and surgical challenge compared with the previous decade. Excellent outcomes may still be achieved by an aggressive approach relying on autogenous vein conduit.
Infrainguinal arterial reconstructions with vein grafts in patients with prior aortic procedures: the influence of aneurysm and occlusive disease.
PURPOSE: This study assessed whether infrainguinal reconstructions with autogenous vein (IR) performed in patients with prior abdominal aortic aneurysm (AAA) repairs have altered graft patency, compared with those in patients who have undergone prior aortobifemoral bypass grafting procedures (ABF) for aortoiliac occlusive disease. METHODS: From 1979 to 1998, 54 patients with prior aortic reconstructions underwent 64 autogenous single-segment saphenous IRs solely for infrainguinal occlusive disease. Included in this cohort were 30 IRs with an earlier AAA repair and 34 IRs with an earlier ABF repair. During the same period, 1274 patients underwent 1642 autogenous vein lower-extremity bypass grafting procedures (LEB). Lower-extremity native arterial (AAA, n = 6; ABF, n = 11) and vein graft diameters (AAA, n = 6; ABF, n = 6) were determined by means of angiography and duplex ultrasonography, respectively. The three reconstruction groups (AAA, ABF, LEB) were compared. RESULTS: The patients in the three groups were similar in sex, indication for operation, proximal and distal anastomotic site, and number of distal runoff vessels. The cumulative 5-year primary graft patency rate in the AAA group (92% +/- 5%) was significantly higher (P <. 001) than that in the LEB group (63% +/- 2%) and the ABF group (44% +/- 11%). Furthermore, cumulative 5-year primary patency was decreased in the ABF group compared with the LEB group (P =.05). A significant increase in both native arterial (P =.001) and vein graft diameter (P <.05) was demonstrated by using linear regression and a Student t test, respectively, in the AAA group compared with the ABF group. CONCLUSION: These data demonstrate that, compared with those in patients without a previous aortic procedure, IRs in patients with prior AAA repairs have significantly improved graft patency, and IRs in patients with prior ABF reconstructions for aortoiliac occlusive disease have significantly decreased graft patency. Larger arterial diameter and altered vein graft adaptation may contribute to the superior long-term outcomes of IRs in patients with prior AAA repairs.
Gene delivery to in situ veins: differential effects of adenovirus and adeno-associated viral vectors.
PURPOSE: Gene transfer offers the potential to modify vein graft biology at the time of surgical implantation. Efficiency of gene delivery, stability of expression, and host responses are critical parameters for candidate vectors. We compared the effects of intraluminal exposure with adenovirus (AD) and adeno-associated virus (AAV) vectors on transgene expression and monocyte adhesion (MA) in treated vein segments. METHODS: Adult New Zealand white rabbits (N = 51) were anesthetized, and the jugular veins were cannulated bilaterally. Veins were gently distended with either vector (2.10(8) to 1.10(10) infective particles/mL) or vehicle (control) for 30 minutes, after which venous flow was restored. AD and AAV vectors encoding for the marker genes beta-galactosidase (LacZ) and green fluorescent protein (GFP) were used. Vessels were explanted 2 to 40 days postinfection for analysis of gene expression (X-gal staining, reverse transcriptase-polymerase chain reaction), MA, and immunohistochemistry. Ex vivo adhesion assays used (51)Cr-labeled THP-1 cells. Statistical significance was tested by using analysis of variance with a P value less than.05. RESULTS: All animals survived, and all treated veins were patent at sacrifice. Intraluminal exposure to AD at a titer of 1.10(9) resulted in near complete transduction of the endothelium at 2 days, with no detectable expression by day 14. At an equal titer of infectious particles, transgene expression was markedly less for AAV at 2 to 7 days, but improved at 2 weeks and persisted to 40 days. MA was significantly increased 2 days after AD exposure (2.7-fold vs control, *P <.002); AAV treatment had no discernible effect on MA. CONCLUSION: AD-mediated gene transfer to vein segments resulted in robust, transient gene expression that disappeared after 2 weeks. In comparison, AAV-mediated gene delivery was less efficient, but resulted in delayed onset, persistent expression beyond 30 days. AD exposure induced an early increase in MA to the vein surface that was not seen with AAV treatment. Current generations of both AD and AAV vectors have significant, albeit different, limitations for vascular gene therapy.
Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial.
BACKGROUND: Cell-cycle blockade by ex-vivo gene therapy of experimental vein grafts inhibits the neointimal hyperplasia and subsequent accelerated atherosclerosis that lead to human bypass-graft failure. In a prospective, randomised, controlled trial, we investigated the safety and biological efficacy of intraoperative gene therapy in patients receiving bypass vein grafts. METHODS: We studied gene therapy that uses decoy oligodeoxynucleotide, which binds and inactivates the pivotal cell-cycle transcription factor E2F. 41 patients were randomly assigned untreated (16), E2F-decoy-treated (17), or scrambled-oligodeoxynucleotide-treated (eight) human infrainguinal vein grafts. Oligonucleotide was delivered to grafts intraoperatively by ex-vivo pressure-mediated transfection. The primary endpoints were safety and inhibition of target cell-cycle regulatory genes and of DNA synthesis in the grafts. Analysis was by intention to treat. FINDINGS: Mean transfection efficiency was 89.0% (SD 1.9). Proliferating-cell nuclear antigen and c-myc mRNA concentrations and bromodeoxyuridine incorporation were decreased in the EF2-decoy group by medians of 73% [IQR 53-84], 70% [50-79], and 74% [56-83], respectively) but not in the scrambled-oligodeoxynucleotide group (p<0.0001). Groups did not differ for postoperative complication rates. At 12 months, fewer graft occlusions, revisions, or critical stenoses were seen in the E2F-decoy group than in the untreated group (hazard ratio 0.34 [95% CI 0.12-0.99]). INTERPRETATION: Intraoperative transfection of human bypass vein grafts with E2F-decoy oligodeoxynucleotide is safe, feasible, and can achieve sequence-specific inhibition of cell-cycle gene expression and DNA replication. Application of this genetic-engineering strategy may lower failure rates of human primary bypass vein grafting.
Improved graft patency and altered remodeling in infrainguinal vein graft reconstruction for aneurysmal versus occlusive disease.
PURPOSE: This study attempted to determine whether autogenous vein used for infrainguinal reconstruction in patients with aneurysmal disease might demonstrate an altered adaptive response compared with those patients who underwent reconstructive surgery for occlusive disease, potentially altering graft patency. METHODS: From 1974 to 1997, 43 patients underwent vein grafting for 60 popliteal artery aneurysms (PAA). RESULTS: In an attempt to monitor early vein graft adaptation, serial graft surveillance by Duplex ultrasound scan was performed in a statistically valid subset of age-, sex-, and distal anastomotic site-matched patients with PAA and patients with occlusive disease (OD; n = 8 PAA; n = 8 OD). Compared with an age-matched and sex-matched cohort of patients (n = 60 grafts in each group) with occlusive disease and who had femoral below-knee bypass grafts (FBP) only, patients undergoing infrainguinal reconstruction for PAA had a higher 5-year primary graft patency (92% +/- 4% for PAA vs 66% +/- 7% for FBP; P <.01). Duplex surveillance demonstrated a progressive increase in arterialized vein graft diameter in the PAA group versus the OD group. In univariant analysis, aneurysmal disease was a significant predictor of final follow-up diameter (P =.002). In a linear regression model, controlling for diameter at first follow-up after bypass grafting, first follow-up diameter was also predictive of final follow-up diameter. CONCLUSION: These data suggested altered remodeling of vein grafts in patients with popliteal artery aneurysm, which may have a beneficial effect on patency.
Molecular identification of the cross-reacting epitope on alphaM beta2 integrin I domain recognized by anti-alphaIIb beta3 monoclonal antibody 7E3 and its involvement in leukocyte adherence.
The monoclonal antibody (mAb) 7E3 directed to the platelet integrin alphaIIb beta3 was tested for its cross-reactivity with the homologous leukocyte integrin alphaM beta2. Nested recombinant fragments of alphaM I domain were expressed as glutathione S-transferase fusion proteins and analyzed for antibody recognition. In enzyme-linked immunosorbent assay, mAb 7E3 bound alphaM I domain fragments containing the amino-terminal sequence Cys128-Ser172, whereas the carboxyl-terminal region Leu173-Pro291 was ineffective. A synthetic peptide designated R1.1 and duplicating the alphaM sequence G127CPQEDSDIAFLIDGSGSIIPHDF150 bound mAb 7E3. In contrast, the adjacent alphaM region F150RRMKEFVSTVMEQLKKSKTLFS172 or a control peptide with a scrambled R1.1 sequence was not recognized by mAb 7E3. Binding of mAb 7E3 to alphaM I domain blocked monocyte and neutrophil adhesion to immobilized fibrinogen and fibrinogen-dependent leukocyte-endothelium bridging, indistinguishably from bona fide anti-beta2 mAb IB4. In contrast, leukocyte binding to stable transfectants expressing intercellular adhesion molecule-1 was not affected by mAb 7E3. Balloon-mediated injury of iliofemoral arteries in rabbits resulted in prominent deposition of fibrinogen and increased monocyte adhesion to the injured vessel, in a reaction inhibited by mAb 7E3, but unaffected by control mAb 14E11. Through its cross-reactivity between alphaIIb beta3 and alphaM beta2, mAb 7E3 may initiate a new class of integrin antagonists, capable of simultaneously targeting platelet and leukocyte adhesion mechanisms in vascular injury.
Retroviral gene transfer: effects on endothelial cell phenotype.
BACKGROUND: Endothelial cells (EC) are an attractive target for somatic cell gene therapy, both for the treatment of cardiovascular disease and for the systemic delivery of recombinant gene products directly into the circulation. Recent evidence, however, suggests that viral transduction may induce unfavorable changes in EC phenotype. We examined the proliferative capacity and cell adhesion molecule (CAM) profile of EC after retroviral gene transfer (GT), employing a clinically relevant ex vivo GT protocol. METHODS: Human umbilical vein EC (HUVEC, N = 14 isolates) were exposed to supernatants containing the MFG.nlsLACZ vector, which codes for a nuclear localized beta-galactosidase. Control HUVEC were exposed to empty virus (CRIP) or no virus (NT). Efficiency of GT was quantitated by direct counting of beta-galactosidase-stained cells on a grid. Proliferation was quantitated by a 1-week assay of viable cell counts. Expression of EC activation molecules (Class II major histocompatibility antigen [MHC II], E-selectin, intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]) was examined using fluorescent cytometry (FACS) at rest and after cytokine stimulation. RESULTS: GT was reproducibly efficient (mean 57%, range 40-77%) using sequential viral exposures without selection. NT, CRIP, and LACZ-transduced HUVEC exhibited identical FACS profiles for E-selectin, ICAM-1, VCAM-1, and MHC II at rest, consistent with a nonactivated state. Upregulation of expression by cytokine was quantitatively similar for all groups. Growth rates were likewise not different between groups. CONCLUSIONS: Retroviral vectors may be employed to achieve high percentages of transduced EC for ex vivo GT without the use of selection. Transduced EC generated in this fashion are not activated, demonstrate an unaltered pattern of inducible CAM expression, and exhibit normal cell growth. The effects of GT on target cell phenotype are likely to be both vector and protocol specific and should be carefully assessed in each case prior to in vivo applications.
Antiplatelet therapy and patency of saphenous-vein bypass grafts in the legs.
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The ideal small arterial substitute: a search for the Holy Grail?
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Effect of renal insufficiency on outcome following infrarenal aortic surgery.
BACKGROUND: This study reviewed the effect of preoperative renal insufficiency on outcome following elective infrarenal aortic surgery. METHODS: The charts of 210 consecutive patients undergoing aortic surgery (occlusive disease, 15%; aneurysmal disease, 78%; or combined disease, 7%) from 1990 to 1995 were categorized into three groups based on preoperative creatinine ([Cr] group 1 Cr < 1.5, n = 171; group 2 Cr 1.5 to 1.7, n = 22; and group 3 Cr > or = 1.8, n = 17) and calculated creatinine clearance ([CrCl] CrCl > 45 mL/min, n = 162 versus CrCl < 45 mL/min, n = 48). Patients with renal artery stenosis or those who required suprarenal cross clamping or emergency procedures were excluded. Differences in postoperative intensive care unit (ICU) stay, ventilator days, dialysis dependence, morbidity, and, mortality were compared. RESULTS: Patients in groups 2 and 3 had an increased incidence of postoperative dialysis dependence (group 2 9%, group 3 8%) when compared with patients in group 1 (group 1: 0%, P < 0.05). Patients in the CrCl > 45 group had a lower mortality rate when compared with patients with a CrCl < 45 (CrCl > 45 0.6% versus CrCl < 45 8%, P <0.05) a lower incidence of dialysis (0% versus 7%, P <0.05), and a lower incidence of postoperative serum creatinine elevation from baseline (CrCl > 45 8% versus CrCl < 45 18%, P <0.05). There was no significant difference in morbidity, ICU stay, or ventilator days between the groups. Upon regression analysis, preoperative CrCl but not Cr was predictive of postoperative mortality (P <0.05). Serum Cr was more predictive than CrCl of impaired renal function postoperatively. CONCLUSIONS: Preoperative CrCl is more accurate than Cr as a predictor of postoperative mortality. Patients with preoperative CrCl < 45 mL/minute who undergo elective aortic surgery have a significant increase in postoperative cardiac-related mortality and dialysis.
The impact of gender on the results of arterial bypass with in situ greater saphenous vein.
BACKGROUND: This 10-year review of in situ saphenous vein bypass surgery was undertaken to assess the impact of gender on infrainguinal arterial reconstruction. PATIENTS AND METHODS: From March 1983 to March 1993, the results of 244 in situ saphenous vein bypasses performed in women were compared with 338 performed in men. Women were older than men (70.9 versus 66.8 years; P < 0.001) and had a higher incidence of hypertension but a lower incidence of coronary artery disease, smoking history, and chronic obstructive pulmonary disease. The primary indication for surgery was limb salvage for both genders (women 70.1%, men 68%; P = not significant [NS]). Men had bypasses to more-distal outflow vessels with 52.5% to the tibial level compared with 42.2% of women (P < 0.003). RESULTS: Women had lower perioperative mortality rates than men (0.8% versus 3.3%; P < 0.025) and a similar incidence of major complications (6.6% versus 7.7%; P = NS), but a higher incidence of significant wound complications (13.5% versus 3.3%; P < 0.001). Life-table evaluation at 10 years after surgery showed no significant differences between women and men in primary graft patency rate (67.8% versus 58.2%; P = NS), secondary patency rate (73.5% versus 77.2%; P = NS ), limb salvage rate (87.9% versus 92%; P = NS) or patient survival rate (35.5% versus 24.4%; P = NS). For bypasses to the tibial arteries, graft patency rates were slightly inferior for women (69.8% versus 81.1%, 5-year secondary patency rate; P < 0.008). Similarly, in bypasses performed for limb salvage, women had lower 5-year primary patency rates than men (60.3% versus 70.3%; P < 0.002). Secondary patency rates in this limb salvage group however, did not differ (75.5% versus 82.8%; P = NS). CONCLUSIONS: Despite small gender differences in the results of in situ bypass grafts for limb salvage and those carried to the tibial level, women had the same overall patency, limb salvage, and survival rates as men after infrainguinal bypass surgery. Treatment of infrainguinal occlusive disease should not vary based on inaccurate perceptions concerning differences in surgical results for men and women.
Femorotibial bypass for claudication: do results justify an aggressive approach?
PURPOSE: The role of infrainguinal arterial reconstructive surgery for claudication is controversial. We reviewed the results of femorotibial bypass procedures performed in a select group of patients with disabling claudication in an attempt to define a role for this aggressive approach. METHODS: Data were retrieved from the vascular registry, and hospital records were obtained for all patients undergoing femorotibial reconstruction for disabling claudication during the past 16 years at Brigham and Women's Hospital. Follow-up interviews were obtained to assess overall health, walking impairment, functional status, and patient satisfaction. RESULTS: During a 16-year period a total of 57 tibial reconstructions were performed in 53 patients for claudication (5% of all infrainguinal vein reconstructions). Autogenous vein conduit was used in all cases, most of which (70%) involved the greater saphenous vein in situ. Distal anastamoses were to the tibioperoneal trunk (12%), anterior tibial (18%), posterior tibial (47%), and peroneal (23%) arteries. Major complications occurred in 9%, and no perioperative deaths occurred. Overall 5-year survival was 54% +/- 15%, and no major amputations were performed. Cumulative primary and secondary graft patency at 5 years were 81% +/- 6% and 86% +/- 5%, respectively. Patency rates were significantly better than those achieved in a concurrent series of tibial bypasses for limb salvage and were equivalent to those achieved with femoropopliteal bypass for claudication. Interviewed patients reported improved walking distance, reduced claudication, and a high degree of overall satisfaction with their operation. CONCLUSION: Results obtained with femorotibial bypass performed for claudication were superior to those obtained for limb salvage and were equivalent to those obtained with femoropopliteal bypass for claudication. The results obtained in this highly selected cohort suggest that patients at low risk with significant functional impairment from claudication, available autogenous vein, and suitable tibial outflow to the ischemic muscular bed can be offered revascularization with the expectation of durable long-term results.