Management of claudicants with low toe-brachial index in a Veteran population.

INTRODUCTION: Intermittent claudication includes a wide spectrum of peripheral artery disease ranging from asymptomatic with reduced perfusion to lifestyle-limiting atherosclerotic disease. The purpose of this study was to evaluate the management of claudicants with a low toe-brachial index (TBI). METHODS: This study was a retrospective review of consecutive patients that presented in 2015 with claudication and a low TBI (<0.6) monitored over 5 years. The patient demographics, co-morbidities, and vascular-related characteristics (ankle-brachial index, TBI, calcified vessels, and wounds) were collected. The patients were separated into two cohorts: diabetics and non-diabetics. The outcomes included progression to chronic limb threatening ischemia (CLTI), interventions (endovascular or open), minor amputations, major amputations, and mortality. RESULTS: A total of 184 patients with 356 limbs were identified as claudicants with a low TBI, and there were 103 diabetics with 81 non-diabetics. The ABI and TBI were similar between the diabetics and non-diabetics, but the diabetics had a significantly higher number of calcified vessels (p < .001) and progression to CLTI (p < .001). The time to revascularization and number of patients that had a revascularization procedure were similar between the two groups, and nearly half of the revascularization procedures were performed within the first 6 months. The major amputation rate trended higher in the diabetic population, and there was a statistically significantly higher rate of minor amputations in the diabetics over the 5 years (Log-rank, p < .001). There was no difference in 5-year survival between diabetics and non-diabetics, and the overall 5-year mortality was 34%. CONCLUSION: Patients presenting with claudication and low TBI, especially with diabetes, are at a higher risk to develop chronic limb threatening ischemia. Claudicants with a low TBI should have closer follow-up and more aggressive risk factor modification to reduce long-term mortality.

Increased Frailty Associated with Higher Long-Term Mortality after Major Lower Extremity Amputation.

BACKGROUND: Frailty assessments have been incorporated into preoperative planning for surgery in the elderly population. Frailty in patients undergoing lower extremity amputation has been associated with increased short-term mortality. We compared 2 frailty scores, modified Frailty Index (mFI) and Risk Analysis Index (RAI), to evaluate the short- and long-term mortality stratified by frailty status after lower extremity amputation. METHODS: A retrospective review at a single Veterans Affairs Medical Center was performed for all patients with peripheral vascular disease that underwent an above or below the knee amputation from 2014 to 2019. Preoperative variables were obtained to calculate the mFI and RAI frailty scores. The frailty scoring systems were used to separate the patients into 3 cohorts: non-frail (mFI <0.45, RAI <20), frail (mFI 0.45-0.55; RAI 20-32), and very frail (mFI >0.55, RAI >32). The frailty groups with each scoring system were compared for 30-day outcomes (readmission, reoperation, adverse events, length of stay) and short- and long-term mortality. RESULTS: A total of 298 patients underwent lower extremity amputation. The number of non-frail patients was 98 (RAI) and 102 (mFI); frail patients 99 (RAI), and 123 (mFI); very frail patients 101 (RAI) and 73 (mFI). For the 30-day outcomes, only length of stay (mFI) was associated with increasing frailty. The short- and long-term mortality was associated with a worse survival with increasing frailty. At 1-year, the mortality by RAI was non-frail 8%; frail 24%, very frail 43% (P < 0.001); the mortality by mFI was non-frail 16%, frail 24%, very frail 41% (P < 0.001). CONCLUSIONS: Preoperative frailty scoring systems identify patients with worse short- and long-term mortality for lower extremity amputation. Frailty scoring should be considered as a screening tool for patients with peripheral vascular disease undergoing lower extremity amputation because of the high rate of frail and very frail patients. The frailty status may provide a more patient-centered approach to counsel patients and their families on the risks and benefits of amputation.

Predictive Accuracy of the American College of Surgeons Risk Calculator in Patients Undergoing Major Lower Extremity Amputation.

BACKGROUND: The American College of Surgeons Risk Calculator (ACS-RC) provides an assessment of a patient's risk of 30-day postoperative complications. The Surgeon Adjusted Risk (SAR) parameter of the calculator allows for ad hoc adjustment of risk based on risk factors not considered by the model. This study aims to evaluate the predictive accuracy of the ACS-RC in vascular surgery patients undergoing major lower-extremity amputation (LEA) and identify additional risk factors that warrant use of the SAR parameter. METHODS: This is a retrospective study of 298 sequential amputations at a single institution. At the population level, the mean of predicted 30-day outcomes from the ACS-RC with a SAR score of 1 (no adjustment necessary) and 2 (risk somewhat higher than estimate) were compared to the rate of observed outcomes. Predictive accuracy at the individual level was completed using receiver operating curve area under the curve (AUC). Logistic regression with respect to mortality was performed over variables not considered by the ACS-RC. Efficacy of selectively utilizing the SAR parameter in predicting mortality was analyzed with a stratified analysis in which patients with risk factors significant for mortality were assigned increased risk. RESULTS: At the population level, ACS-RC grossly underpredicted serious complications, SSI, VTE, and unplanned RTOR, while overpredicting mortality and cardiac complications. At the individual level, SAR1 was more predictive for serious complications (AUC = 0.624), SSI (AUC = 0.610), and unplanned RTOR (AUC = 0.541). Conversely, SAR2 was more predictive for mortality (AUC = 0.709), cardiac complications (AUC = 0.561), and VTE (AUC = 0.539). Logistic regression identified history of CVA with a residual deficit (OR = 4.61, P = 0.033) and ischemic rest pain without tissue loss (OR = 4.497, P = 0.047) as independent risk factors for postoperative mortality. Stratified analysis with utilization of the SAR2 based on the 2 independent risk factors improved AUC in predicting mortality (AUC 0.792 from 0.709). CONCLUSIONS: Major LEAs are associated with high perioperative morbidity and mortality. In a veteran population, the ACS-RC showed mixed predictability at the population level and fair predictability at the individual level with regards to postoperative outcomes. Rest pain without tissue loss and history of CVA with residual deficit were identified as risk factors for postoperative mortality. Although ad hoc adjustment with the subjective SAR modifier based on the presence of these 2 risk factors increased the calculator's accuracy, this study highlights some potential limitations of the ACS-RC when applied to vascular surgery patients undergoing major LEA.

A nationwide analysis of 30-day readmissions related to critical limb ischemia.

Objectives There is paucity of information regarding critical limb ischemia-related readmission rates in patients admitted with critical limb ischemia. We studied 30-day critical limb ischemia-related readmission rate, its predictors, and clinical outcomes using a nationwide real-world dataset. Methods We did a secondary analysis of the 2013 Nationwide Readmissions Database. We included all patients with a primary diagnosis of extremity rest pain, ulceration, and gangrene secondary to peripheral arterial disease. From this group, all patients readmitted with similar diagnosis within 30 days were recorded. Results Of the total 25,111 index hospitalization for critical limb ischemia, 1270 (5%) were readmitted with a primary diagnosis of critical limb ischemia within 30 days. The readmission rate was highest (9.5%) for the group that did not have any intervention (revascularization or major amputation) and was lowest for surgical revascularization and major amputation groups (2.6% and 1.3%, P value <0.001 for all groups). Severity of critical limb ischemia at index admission was associated with a significantly higher rate of 30-day readmission. Critical limb ischemia-related readmission was associated with a higher rate of major amputation (29.6% vs. 16.2%, P<0.001), a lower rate of any revascularization procedure (46% vs. 62.6%, P<0.001), and a higher likelihood of discharge to a skilled nursing facility (43.2% vs. 32.2%, P<0.001) compared to index hospitalization. Conclusions In patients with primary diagnosis of critical limb ischemia, 30-day critical limb ischemia-related readmission rate was affected by initial management strategy and the severity of critical limb ischemia. Readmission was associated with a significantly higher rate of amputation, increased length of stay, and a more frequent discharge to an alternate care facility than index admission and thus may serve as a useful quality of care metric in critical limb ischemia patients.

Decellularized tissue-engineered blood vessel as an arterial conduit.

Arterial tissue-engineering techniques that have been reported previously typically involve long waiting times of several months while cells from the recipient are cultured to create the engineered vessel. In this study, we developed a different approach to arterial tissue engineering that can substantially reduce the waiting time for a graft. Tissue-engineered vessels (TEVs) were grown from banked porcine smooth muscle cells that were allogeneic to the intended recipient, using a biomimetic perfusion system. The engineered vessels were then decellularized, leaving behind the mechanically robust extracellular matrix of the graft wall. The acellular grafts were then seeded with cells that were derived from the intended recipient--either endothelial progenitor cells (EPC) or endothelial cell (EC)--on the graft lumen. TEV were then implanted as end-to-side grafts in the porcine carotid artery, which is a rigorous testbed due to its tendency for graft occlusion. The EPC- and EC-seeded TEV all remained patent for 30 d in this study, whereas the contralateral control vein grafts were patent in only 3/8 implants. Going along with the improved patency, the cell-seeded TEV demonstrated less neointimal hyperplasia and fewer proliferating cells than did the vein grafts. Proteins in the mammalian target of rapamycin signaling pathway tended to be decreased in TEV compared with vein grafts, implicating this pathway in the TEV's resistance to occlusion from intimal hyperplasia. These results indicate that a readily available, decellularized tissue-engineered vessel can be seeded with autologous endothelial progenitor cells to provide a biological vascular graft that resists both clotting and intimal hyperplasia. In addition, these results show that engineered connective tissues can be grown from banked cells, rendered acellular, and then used for tissue regeneration in vivo.

Arterial shear stress reduces eph-b4 expression in adult human veins.

Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

Allogeneic human tissue-engineered blood vessel.

BACKGROUND: Arterial bypass graft implantation remains the primary therapy for patients with advanced cardiovascular disease; however, there is no available synthetic small-diameter vascular graft. METHODS: Tissue-engineered vessels were grown from human smooth muscle cells that were seeded on a biodegradable scaffold using a biomimetic perfusion system. The human tissue-engineered vessels (hTEV) were decellularized by a two-step process using a combination of detergents and hypertonic solutions. The mechanical characteristics were assessed by suture retention strength and burst pressure. The decellularized hTEV were implanted as aortic interpositional grafts in nude rats to evaluate in vivo performance as an arterial graft over a 6-week period. RESULTS: The human tissue-engineered structure formed a vessel composed of smooth muscle cells and the extracellular matrix proteins, including collagen. After decellularization, the collagen matrix remained intact while the cellular components were removed. The mechanical strength of the hTEV after decellularization was similar to human vein in vitro, with a burst pressure of 1,567 ± 384 mm Hg (n = 3) versus 1,680 ± 307 mm Hg for human saphenous vein. The hTEVs had a high patency rate (four of five grafts) without evidence of rupture or aneurysm over a 6-week period as an aortic interpositional graft in a nude rat model. Histologic analysis showed a thin neointima with a confluent endothelium and a subendothelial layer of smooth muscle cells on the explanted tissue-engineered vessels. Transmission electron microscopy on the explanted tissue demonstrated elastin formation in the neointima and intact residual collagen fibers from the tissue-engineered vessel. CONCLUSIONS: The hTEV had a high patency rate and remained mechanically stable as an aortic interpositional graft in a nude rat. The vessel supported the growth of a neointima with endothelial cells and smooth muscle cells. The host remodeling suggested the engineered matrix had a positive effect to create a regenerated vascular graft.

Improved porosity of electrospun poly (Lactic-Co-Glycolic) scaffolds by sacrificial microparticles enhances cellular infiltration compared to sacrificial microfiber.

Electrospinning is a technique used to fabricate nano-/microfiber scaffolds for tissue engineering applications. However, a major limitation of electrospun scaffolds is the high packing density of fibers that leads to poor cellular infiltration. Thus, incorporation of a water soluble sacrificial porogen, polyethylene oxide (PEO), was utilized to fine-tune the porous fraction of the scaffolds and decrease fiber packing density. Poly(lactic-co-glycolic) acid (PLGA) scaffolds were either co-electrospun with sacrificial PEO microfibers or co-electrosprayed with sacrificial PEO microparticles at three different extrusion rates to control the relative morphology and dose of PEO. A dose-dependent response in PLGA scaffold bulk porosity and pore area was noted as PEO content was increased. Notably, PLGA scaffolds after removal of sacrificial PEO microparticles significantly increased the porous fraction and pore area approximately 8, 10, and 14% and 46, 20, and 33 µm2, respectively, relative to the analogous PEO microfiber scaffold. The tensile properties of the more porous PLGA scaffolds after PEO microparticle removal, remained stable for all extrusion rates of PEO tested, relative to the PLGA scaffolds after PEO microfiber removal. Histological analysis revealed that removal of PEO microparticles significantly increased the depth of cellular migration through the PLGA scaffolds, relative to PEO microfiber scaffolds, with maximum migratory depths of 1120 µm versus 150 µm over 28 days, respectively. Additionally, depth of cellular infiltration responded dose-dependently in the PEO microparticle scaffolds, whereas in the PEO microfiber scaffolds there was no correlation. Further analysis with Masson's Trichrome staining and electron microscopy revealed that collagen density and depth of deposition substantially increased in PLGA scaffolds after removal of PEO microparticles relative to PEO microfibers. Thus, this study demonstrates an effective strategy to control the porous fraction of electrospun scaffolds via the incorporation of sacrificial PEO microparticles, without significant decreases in mechanical properties, thereby enhancing cellular infiltration and subsequent extracellular matrix deposition.

Telemedicine at the VA: Examining smartphone connectivity rates to VA video connect and doximity dialer video.

Background: Telemedicine usage has accelerated as a result of the COVID-19 pandemic, raising concerns those without the necessary technology and digital literacy to participate may face increasing health disparities. In this study, we examined the rates at which veterans are able to connect to two common telemedicine applications: VA Video Connect (VVC) and Doximity Dialer Video (DV). Methods: Participants were selected from a pool of vascular surgery patients seen from August 2020 to October 2021 at a single Veterans Affairs medical center. Participants had to be >50 years old and not previously participated in a video visit. Eligible veterans were asked their interest participating in video visits and if they owned a smartphone. Those who met the eligibility requirements were tested on their ability to connect to both VVC and DV with minimal assistance. The connectivity rate for both platforms was recorded, and basic demographic and medical history information was collected. Results: One-hundred-four veterans participated in the study, with an average age of 70 ± 7 years. Seventy-four participants (71%) expressed interest in video visits, and 52 (70%) owned a smartphone. Forty-five smartphone owners (87%) successfully connected to DV, whereas 19 (37%) successfully connected to VVC (p < 0.001). VVC connectivity decreased with increasing age-group: 50-59 = 80%, 60-69 = 44%, ≥70 = 18% (p = 0.02). Conclusions: Older veterans demonstrate difficulty connecting to VVC. The VHA is taking important steps to streamline usability of VVC, however continued expansion of support programs is necessary to improve access and reduce healthcare disparities in this population.

Surgical risk calculators in veterans following lower extremity amputation.

OBJECTIVE: To evaluate the accuracy of multiple risk calculators for 30-day mortality on patients undergoing major lower extremity amputation. METHODS: The actual 30-day mortality at a single Veterans Affairs institution was compared to the predicted outcome from the following risk calculators: ACS-NSQIP, VASQIP, amputation scoring tool (AST), and POTTER elective. RESULTS: The overall calculated 30-day mortality was similar to the actual mortality with the VASQIP and POTTER elective risk calculators, while the NSQIP and AST over-estimated the 30-day mortality. The predictive accuracy of the POTTER and NSQIP risk calculators were moderate (AUC >0.7), and fair for the VASQIP and AST. CONCLUSION: Risk assessment tools can provide adjunctive data on predicted 30-day mortality in patients undergoing major lower extremity amputation. In our study, there were differences in predictability of the risk calculators for lower extremity amputation that should be considered when utilizing a risk assessment tool to improve physician-patient shared decision-making.

Tissue-engineered vessel derived from human fibroblasts with an electrospun scaffold.

Advanced cardiovascular disease often requires surgical revascularization for small diameter arterial bypass procedures, and there is a need for alternative grafts in those patients lacking autologous vein. A decellularized biological vessel with the characteristics of a small artery and the ability to remodel in vivo could replace currently available bypass grafts. In this study, a biodegradable electrospun scaffold was specifically designed to be placed in a biomimetic perfusion system to generate a tissue-engineered vessel from human dermal fibroblasts. The polyglycolic acid electrospun scaffold was co-electrosprayed with a sacrificial porogen microparticle, polyethylene oxide, to increase porosity and pore size. After a 10-week culture period in the biomimetic system, the tissue-engineered vessel derived from human fibroblasts was further processed with decellularization to form an allogeneic tissue-engineered vessel. The tissue-engineered vessel had a similar morphology by histological staining for collagen and elastin before and after decellularization. The mechanical properties (burst pressure, ultimate tensile strength, and elastic modulus) remained stable after decellularization and were on the same magnitude as a human saphenous vein. The decellularization processing demonstrated no loss of collagen, near complete removal of DNA, and no presence of intracellular proteins. The decellularized tissue-engineered vessel supported the growth of endothelial cells on the surface, and fibroblasts were able to migrate into the midportion of the matrix. Therefore, an electrospun scaffold provides a versatile biomaterial to create a decellularized tissue-engineered vessel derived from human dermal fibroblasts with morphological and mechanical properties for use as a small diameter vascular graft.

Tissue engineered vessel from a biodegradable electrospun scaffold stimulated with mechanical stretch.

A tissue engineered vessel has the potential to provide an alternative small diameter vascular graft for patients with cardiovascular disease in need of surgical revascularization. In this study, a polyglycolic acid (PGA) electrospun scaffold seeded with human dermal fibroblasts was stimulated with circumferential mechanical stretch by a pulsatile perfusion system. The PGA scaffold was fabricated using a custom electrospinning set-up to co-electrospray a sacrificial polyethylene oxide microparticle to increase pore size and bulk porosity. The tissue engineered vessel exposed to circumferential mechanical stretch was compared to an engineered vessel cultured under static conditions without any mechanical stimulation. The histology cross-sections demonstrated a similar thickness of engineered vessels with mechanical stretch and static, but on Masson's Trichrome stain there was nearly twice the amount of staining for collagen. The collagen content was quantified, and the collagen content was 60% greater in the human tissue engineered vessel exposed to mechanical stretch compared to the static vessel. The total collagen cross-linking was similar, but on a per collagen basis there was significantly more cross-linking in the static vessel over the stretch vessel. The stress-strain curve of the tissue engineered vessel with mechanical stretch demonstrated a statistically significantly greater ultimate tensile strength (UTS) of 1.86 ± 0.14 MPa (n = 6) and elastic modulus (EM) of 7.62 ± 0.39 MPa (n = 6) versus the static engineered vessel UTS of 0.31 ± 0.07 MPa (n = 5) and EM of 1.37 ± 0.21 MPa (n = 5). The primary determinant of the mechanical properties of the tissue engineered vessel correlated to the collagen content with minimal contribution of the collagen cross-linking. Therefore, the versatile properties of an electrospun scaffold are ideal in combination with a biomimetic culture system to generate a tissue engineered vessel composed of extracellular matrix suitable as a vascular graft.

The improvement of cell infiltration in an electrospun scaffold with multiple synthetic biodegradable polymers using sacrificial PEO microparticles.

Electrospinning is a fabrication technique to generate three dimensional scaffolds with a fiber structure that imitates extracellular matrix for tissue engineering constructs. The versatile characteristics of the electrospinning process yields designer scaffolds made of biodegradable polymers or natural proteins with controllable fiber diameters, biodegradation, and mechanical properties. A limitation of conventional electrospun scaffolds is the dense fiber packing with low porosity that leads to poor cell infiltration. Electrospraying sacrificial polyethylene oxide (PEO) microparticles in combination with electrospun scaffolds are a method to increase porosity. We report the effectiveness of electrospraying PEO microparticles to increase porosity of the most commonly used biodegradable polymers: polyglycolic acid (PGA), poly (lactic-co-glycolic) acid (PLGA), and polycaprolactone (PCL). The biodegradable polymer electrospun scaffolds with the sacrificial PEO microparticles were found to have improved cell proliferation and infiltration with human fibroblasts compared to conventional electrospun scaffolds. The mechanical properties of the more robust PGA and PLGA had minor changes, but the more elastic PCL was observed to be weaker and less stiff after the removal of the PEO microparticles. Therefore, this study found PEO microparticles can increase porosity and cell infiltration with stable mechanical properties for a wide variety of biodegradable polymers in electrospun scaffolds.

Coumarins and pyranocoumarins, potential novel pharmacophores for inhibition of measles virus replication.

A series of coumarin and pyranocoumarin analogues were evaluated in vitro for antiviral efficacy against measles virus (MV), strain Chicago. Of the 22 compounds tested for inhibition, six were found to have selectivity indices greater than 10. These were compounds 5-hydroxy-7-propionyloxy-4-propylcoumarin (2a), 5,7-bis(tosyloxy)-4-propylcoumarin (7); 5-hydroxy-4-propyl-7-tosyloxy-coumarin (8); 6,6-dimethyl-9-propionyloxy-4-propyl-2H,6H-benzo[1,2-b:3,4-b']dipyran-2-one (9); 6,6-dimethyl-9-pivaloyloxy-4-propyl-2H,6H-benzo[1,2-b:3,4-b']dipyran-2-one (10); and 7,8-cis-10,11,12-trans-4-propyl-6,6,10,11-tetramethyl-7,8,9-trihydroxy-2H,6H,12H-benzo[1 ,2-b:3,4-b':5,6-b'']tripyran-2-one (18). Three of the active drugs were propyl coumarin analogues (2a, 7 and 8), two were dipyranone or chromeno-coumarins (9 and 10), and one was a benzotripyranone with a coumarin nucleus (18). Some appeared to be rather specific and potent inhibitors of MV with EC50 values ranging from 0.2 to 50 microg/ml and the majority of the EC50 values being less than 5 pg/ml. The compounds inhibited an additional nine strains of MV, and in virucidal tests the drugs did not physically disrupt the virion to inhibit virus replication. The inhibitory activity for one of the compounds tested (7) was somewhat dependent on virus concentration and it was still active when added to cells up to 24 h after virus exposure. When used in combination with ribavirin, compound 7 appeared not to profoundly affect the antiviral efficacy of ribavirin or its cell-associated toxicity. However, a slightly antagonistic MV-inhibitory effect was observed at the highest concentration of ribavirin used in combination with most concentrations of compound 7 tested. This and related compounds may be valuable leads in the development of a potent and selective class of MV inhibitors that could be used in future in the clinic.

Longitudinal impedance is independent of outflow resistance.

BACKGROUND: Many investigators have measured outflow resistance (R) following peripheral bypass procedures, but correlations with graft patency have been weak. This is because the primary determinants of graft patency are the size and quality of the conduit, not its outflow bed. Efforts at separating conduit resistance from outflow resistance have been unsuccessful. Recently, the concept of longitudinal impedance ( integral Z(L)) has been suggested as a measure of conduit resistance independent of outflow resistance. The purpose of this in vitro experiment was to test the hypothesis that integral Z(L) is independent of R within physiologically relevant ranges. METHODS: Rigid polyethylene tubing of known internal diameter and length (4.3 mm, 375 cm) was perfused with a glycerin/saline mixture mimicking the viscosity of blood (4.1 cp), utilizing a variable pulsatile pump and Windkessel, with outflow into multiply branched tubes of decreasing diameter simulating the hemodynamic conditions of arterial bypass. Flow and pressure were measured using ultrasonic transit time and catheter transduction, respectively, and waveforms digitized at 200 Hz. Flow was varied while maintaining "systemic" pressure and resistance. After Fourier transformation, integral Z(L) was calculated as deltaP/Q at each harmonic and integrated over 4 Hz. RESULTS: integral Z(L) calculations were remarkably reproducible within the same day with a coefficient of variation (CV) = 4.0% (at 100 dyne. s/cm(5); n = 4) or over 4 successive days (CV = 4.3%). Furthermore, integral Z(L) was largely independent of R over the physiologic range tested, with integral Z(L) remaining relatively constant as R was increased sixfold. CONCLUSION: integral Z(L) is a consistent and reproducible measure of conduit resistance independent of R over a wide physiologic range. It may be useful for measuring the adequacy of bypass graft conduits.