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OBJECTIVE This retrospective review examines open operative management of dialysis-dependent ischemic nephropathy among consecutive hypertensive adults. METHODS From February 1987 through July 2005, 820 patients underwent open operative repair of 1220 kidneys at our center. A subgroup of 45 hypertensive patients (19 women, 26 men; mean age, 68 ± 9 years; mean BP, 205 ± 29/99 ± 20) considered permanently dialysis-dependent prior to renal artery (RA) repair forms the basis of this report. Estimated glomerular filtration rate (EGFR) was determined from serial serum creatinine measures 14 weeks before and after RA repair. The mean rate of change of EGFR was estimated before and after RA repair using linear regression analysis. Analysis of kidney status and change in EGFR was performed. The relationship between renal function response after an operation and survival was determined by the product-limit method. RESULTS Renal artery repairs to 73 kidneys included RA bypass (44 repairs: 22 saphenous vein repairs and 22 prosthetic grafts), RA endarterectomy (25 repairs; 13 transrenal and 12 transaortic), and RA reimplantation (4 repairs). Thirty-five patients had bilateral procedures, including 4 procedures to solitary kidneys. Eighteen patients had combined aortic repair (13 AAA, 5 aortic occlusions). Of 28 RA occlusions, 25 were repaired. Three nephrectomies were performed for unreconstructable RA to a nonfunctioning kidney. After RA repair, 2 patients died (4.4%) within 30 days of operation or in-hospital. Twenty-nine of 43 (67%) surgical survivors stopped being dialysis dependent. Among patients removed from dialysis, postoperative EGFR ranged from 10.0 to 91.1 mL/min/1.73 m2 (mean: 41.7 ± 18.6 mL/min/1.73 m2). Four patients initially removed from dialysis progressed to eventual dialysisdependence on follow-up. Removal from dialysis was associated with a more rapid decline in preoperative EGFR (mean slope per week loge EGFR: −0.1489 ± 0.0180 off dialysis; −0.0748 ± 0.0236 on dialysis; p = .01); however, EGFR did not differ statistically after unilateral or bilateral RA procedures (mean: 25.8 ± 7.7 mL/min/1.73 m2 unilateral versus 44.6 ± 3.8 mL/min/1.73 m2 bilateral; p = .06). On follow-up, improved survival was observed for patients removed from dialysis compared with patients who remained dialysis dependent (p = 0.003). CONCLUSION Open operative management of dialysis-dependent ischemic nephropathy can remove selected patients from dialysis. Beneficial renal function response was associated with a rapid decline in preoperative renal function. Compared with that of patients who remained dialysis dependent, the survival of patients who could cease dialysis after the operation was was improved.

Purpose This retrospective review describes the surgical management and clinical outcome for renal artery aneurysms (RAAs) in 62 consecutive patients. Methods From January 1987 through July 2003, 804 patients had operative renal artery (RA) repair involving 1206 kidneys at our center. A subgroup of 62 patients (42 women, 20 men; mean age 46 ± 18 years) received repair of 72 RAAs. Demographic data, comorbidity, and surgical technique were examined. Blood pressure and renal function response were determined. Patency of repair was evaluated by renal duplex sonography. Primary patency and patient survival were estimated by life-table methods. Tests of association were performed using χ 2 and the Student t tests. Results Seventy-two RAs were repaired for RAA with a mean diameter of 2.6 cm (range, 1.3 to 5.5 cm). Bilateral RAAs were present in 21 patients. Associated conditions included fibromuscular dysplasia, atherosclerosis, and arteritis in 54%, 35%, and 7%, respectively. Hypertension was present in 89% (mean blood pressure, 171 ± 35/95 ± 19 mm Hg; mean medications, 2.2 ± 1.2 drugs) and renal insufficiency was present in 8% (mean serum creatinine, 1.9 ± 0.6 mg/dL). RAA repair included bypass (67%), aneurysmorrhaphy (15%), or a combination (17%). One planned nephrectomy (1%) was performed for un-reconstructable disease. Branch RA reconstruction in 78% used ex vivo cold perfusion in 50%, in situ cold perfusion in 29%, and warm in situ repair in 21%. Of 9 bilateral RAA repairs, 7 (78%) were staged and 2 (22%) were simultaneous. Combined aortic reconstruction was required in 6 (10%) patients. Perioperative death occurred in 1 patient (1.6%), and significant morbidity was observed in 8 patients (12%). Hypertension was considered improved in 54%, cured in 21%, and unchanged in 25% at mean follow-up of 48 months (range, 1-156 months). Among patients with renal insufficiency, renal function was improved in 3 (60%), unchanged in 1 (20%), and declined in 1 (20%). Follow-up patency (mean, 33 months; range, 1-118 months) was determined for 64 (91%) RA reconstructions. Product-limit estimate of primary patency at 48 months was 96%. Product-limit estimate of survival was 91% at 120 months. Conclusion RAAs were repaired with low morbidity and mortality. Complex branch RAA repair using cold perfusion preservation and ex vivo techniques resulted in no unplanned nephrectomy, with an estimated primary patency of 96% at 48 months. Beneficial blood pressure response was observed in the majority of hypertensive patients. These results support selective surgical management of RAA.

Purpose: The purpose of this investigation was to estimate the population-based prevalence of renovascular disease (RVD), defined as ≥60% diameter-reducing renal artery stenosis or occlusion, and to define its associations with age, gender, race, and other potential risk factors among participants in the Cardiovascular Health Study (CHS). Methods: The CHS is a multicenter, longitudinal cohort study of cardiovascular disease risk factors, morbidity, and mortality among free-living adults of more than 65 years of age. As part of an ancillary investigation, participants in the Forsyth County cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD. RVD was defined as stenosis with a focal renal artery peak systolic velocity exceeding 1.8 m/s in the main renal artery and defined as occlusion when an imaged renal artery lacked a Doppler signal. Demographic and atherosclerotic risk factor data were gathered as part of the baseline CHS examination. Univariable tests of association were performed with χ 2 and Student t tests and logistic regression analysis. Multivariate associations were examined with logistic regression analysis. Results: Eight hundred seventy CHS participants underwent RDS. Of these examinations, 834 (96%) were technically adequate to define the presence or absence of RVD. The RDS study cohort had a mean age of 77.2 ± 4.9 years and consisted of 63% women and 37% men. Participant race was 76% white and 23% African American. The overall prevalence rate of RVD was 6.8%. Among the 57 patients with RVD, 50 (88%) had unilateral disease and seven (12%) had bilateral disease. Seven cases were seen of renal artery occlusion, including one case with contralateral renal artery stenosis. The mean ages of patients with and without RVD were 78.7 ± 5.7 years and 77.1 ± 4.9 years ( P = .018). RVD was present in 5.5% of women and 9.1% of men ( P = .053). RVD was present in 6.9% of white participants and 6.7% of African American participants ( P = .933). Multivariate analysis revealed increasing participant age ( P = .028; odds ratio, 1.34; 95% CI, 1.03, 1.73), high-density lipoprotein cholesterol levels of less than 40 mg/dL ( P = .003; odds ratio, 2.63; 95% CI, 1.40, 4.93), and increasing systolic blood pressure ( P = .007; odds ratio, 1.44; 95% CI, 1.10, 1.87) to be significantly and independently associated with the presence of RVD. Conclusion: This investigation provides the first population-based estimate of the prevalence of RVD among free-living, elderly black and white Americans. RVD was present in 6.8% of the study cohort. RVD showed no association with ethnicity. However, its presence was significantly and independently associated with increasing age, low high-density lipoprotein cholesterol levels, and increasing systolic blood pressure. (J Vasc Surg 2002;36:443-51.)

Purpose: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. Methods: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 ± 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. Results: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age ( P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure ( P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged ( P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened ( P =.03; hazard ratio, 2.2; CI [1.1, 4.5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. Conclusion: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy. (J Vasc Surg 2000;32:472-82.)

The saphenous vein is among the most commonly used conduits for renal artery revascularization in adults. Vein grafts are more durable in the renal artery bed than in coronary and peripheral beds, and mechanisms of potential graft failure vary. Coronary vein grafts often fail because of atherosclerotic degeneration, whereas lower extremity grafts fail because of intimal hyperplasia or progression of underlying disease. In contrast, renal vein grafts may dilate over time but seldom fail. This may relate to the distinct hemodynamic environment of the renal bed with low-resistance, high-velocity blood flow. However, frank aneurysmal degeneration of renal vein grafts is rare with only a single report of rupture in the literature. We report an additional case of rupture of a late graft aneurysm and review the literature and our own experience with renal revascularization to underscore the rarity of this serious complication. The saphenous vein for aortorenal bypass grafting continues to be a favorable conduit for renal revascularization. Long-term duplex ultrasound scanning follow-up is recommended to survey the reconstructed artery and perhaps more important, to evaluate progression of subclinical disease in the contralateral renal artery. (J Vasc Surg 2000;32:612-5.)

Background —Angiotensin II may contribute to atherogenesis by facilitating the proliferative and inflammatory response to hypercholesterolemia. This study determined, in a primate model of diet-induced atherosclerosis, the effect of AT 1 blockade on fatty-streak formation, plasma lipids, and surrogate markers of vascular injury. Methods and Results —Male cynomolgus monkeys fed a diet containing 0.067 mg cholesterol/kJ for 20 weeks were given losartan (180 mg/d, n=6) or vehicle (n=8) for 6 weeks starting at week 12 of the dietary regimen. Arterial pressure, heart rate, plasma total and lipoprotein cholesterol concentrations, and lipoprotein particle sizes and subclass distributions were unaffected by treatment. Losartan caused significant ( P P P Conclusions —This study demonstrates for the first time an antiatherogenic effect of AT 1 receptor blockade in nonhuman primates. Losartan inhibited fatty-streak formation through mechanisms that may include protection of LDL from oxidation and suppression of vascular monocyte activation and recruitment factors.

We propose that Ang II exerts an as yet uncharacterized immunomodulatory effect on monocyte maturation, differentiation, or extravasation, which may depend on the myelomonocytic phenotype. Since the myelopoietic process originating at stem cells and culminating in release to the blood is at least 6 days, it is conceivable that the observation of reduced monocyte CD11b expression two weeks after completion of losartan treatment indicates a suppression of the CD11b phenotype in newly released CD14(+)/CD45(+) monocytes. Other studies employing suppression of AT(1)-receptors with deoxy-oligonucleotides have reported effects on blood pressure that surpass those predicted by the duration of the treatment.(87) These data would suggest that it is possible to interrupt a stimulatory signal by Ang II through a gene-related mechanism that in our experiments may reside in the mechanisms that regulate myelopoiesis. While our knowledge of the role of Ang II in the regulation of monocyte formation and function is incomplete, we have taken a first step in attempting to synthesize the data described above into a comprehensive hypothesis for further evaluation of the factors that initiate atherogenesis. Such effects may crucially contribute to the clinical benefit of AT(1)-receptor antagonists, independent of depressor effects, and may represent a paradigm for novel, anti-inflammatory actions by this class of drugs.

Objective This report examines the blood pressure and renal function response in 20 consecutive patients after secondary renal revascularization following failed operative repair. Background Data Most reports describing operative failure of renal artery (RA) repair emphasize the technical aspects of redo RA reconstruction and the immediate blood-pressure response to secondary operation. This report examines the eventual renal function and estimated survival after secondary intervention. Methods Primary methods of RA reconstruction, primary blood pressure and renal function responses, and causes of failed RA repair were defined for 20 patients requiring reoperation for recurrent hypertension or renal insufficiency. These parameters were compared with secondary procedures and eventual blood pressure and renal function response. The eventual outcome for these 20 patients was compared with 514 patients managed by primary renal revascularization during the same period. Results Failure of primary RA repair correlated with complex fibromuscular dysplasia requiring branch ex vivo reconstruction (p = 0.020). RA thrombosis frequently required nephrectomy (83%), whereas RA stenosis was successfully reconstructed (91%; p = 0.001). Primary and secondary blood-pressure responses were equivalent (94% vs. 95% cured or improved); however, primary and eventual renal function responses differed significantly (p = 0.015), with seven patients dialysis-dependent on follow-up. Eventual dialysis dependence was associated with preoperative azotemia (p = 0.022), bilateral failure of primary RA repair (p = 0.007), and an increased risk of follow-up death (p = 0.002). Considering all 534 patients, failed RA repair demonstrated a significant and independent association with eventual dialysis dependence and decreased dialysis-free survival. Conclusions Contemporary rates of reoperation after surgical RA repair are low. In properly selected patients, beneficial blood-pressure response is reliably observed after both primary and secondary operative procedures. However, secondary procedures are associated with a significant and independent risk of eventual dialysis dependence.

Hypertension in blacks differs in a quantitative sense from hypertension in whites; it occurs in blacks with greater frequency and severity and at a younger age when compared with whites. In addition, elevated blood pressure at any level is associated with increased cardiovascular morbidity and mortality in black patients. Several mechanisms have been suggested to account for this form of hypertension, implying that hypertension in black patients is intrinsically different from that in whites. Although these mechanisms remain unproven, it has generally been accepted that correctable renovascular disease and renovascular hypertension (RVH) occur infrequently in blacks; the authors, however, will review preliminary populationbased data which suggest that the presence of renal artery disease is not determined by raceor ethnicity. In addition, the prevalence of renovascular disease in a large group of consecutive hypertensive subjects will be presented.Finally, the blood pressure and renal function response after surgical renal artery repair in blacks will be compared with whites treated at the authors' institution. Taken collectively, these data and clinical experience support the search for and treatment of renal artery disease in properly selected hypertensive blacks. KEY INDEXING TERMS: Hypertension; Renovascular disease; Renovascular hypertension.[Am J Med Sci 1998;315(5):337-342.]

Purpose: The intimal hyperplasia hypothesis that equates lumen narrowing after arterial injury with intimal mass has recently been challenged. Evidence has emerged to suggest that lumen narrowing is caused in large part by changes in artery wall geometry rather than intimal mass per se. We have begun to explore this hypothesis in a unique nonhuman primate model of atherosclerosis. Methods: Monkeys who were fed an atherogenic diet for 3 to 5 years underwent experimental angioplasty of the left iliac artery. The contralateral iliac artery served as an intraanimal control. Arteries were removed 2, 4, 7, 14, 28, or 112 days later for analysis (6 or 13 per time point). Angioplasty dilated arteries by fracturing atheroma and stretching or tearing the media. Cross-sections of injured arteries were analyzed for expression of extracellular matrix components and cell surface integrins that are important in wound healing. Antibodies, riboprobes, or histochemical stains specific for fibrin, hyaluronan, versican (chondroitin sulfate–containing proteoglycan), procollagen-I, elastin, and the α 2 β 1 and α V β 3 integrins were used. Results: A thin mural thrombus was seen at sites of denudation and plaque fracture (days 2 to 7). This provisional matrix was invaded by leukocytes (days 2 to 4) and α-actin–positive smooth muscle cells (SMCs; days 4 to 7). Thrombus was replaced by SMCs expressing hyaluronan and the associated versican proteoglycans (day 14). Versican was expressed throughout the neointima as it enlarged (day 28), but expression later subsided (day 112). Procollagen-I expression initially increased in the adventitia (day 4) and then in the forming neointima (day 14). Procollagen-I expression was found to persist within the adventitia and in the neointima in SMCs nearest the lumen (days 28 to 112). Elastin staining was prominent within the mature neointima (day 112) but not at earlier time points. Integrin expression also increased within the injured artery wall. α V β 3 staining (fibrin[ogen] receptor) increased in the injured media (days 2 to 7) and was then seen throughout the early neointima (day 7). Low level expression of α V β 3 subsequently persisted within the forming neointima (day 28). α 2 β 1 (collagen receptor) expression increased in the neointima in SMCs nearest the lumen (day 28). Conclusions: Lumen narrowing after angioplasty in this model of atherosclerosis is caused largely by decreased artery wall diameter. The pattern of matrix and integrin expression within the injured artery wall is in many ways analogous to that of healing wounds. These observations suggest that tissue contraction may play a role in lumen narrowing at sites of arterial reconstruction. Strategies to inhibit wound contraction may prove effective in preventing restenosis. (J Vasc Surg 1998;27:96-108.)

Purpose: The relationship between lumen narrowing, intimal hyperplasia, and wall remodeling after angioplasty was explored in a nonhuman primate model of atherosclerosis.Methods: Cynomolgus monkeys (n = 37) used in long-term atherosclerosis studies underwent left iliac artery balloon injury. The uninjured right iliac artery served as a reference segment for intraanimal comparisons. One month later iliac arteries were fixed by perfusion (100 mm Hg) and removed for cross-sectional analysis to determine mean values for lumen area (LA), intimal area (IA), internal elastic lamina area (IELA), plaque burden (IA/IELA), and depth of wall injury. Values for each balloon-injured iliac artery were normalized to the contralateral uninjured iliac artery (percent of control), and linear regression analysis was performed comparing LA with IA, with IELA, and with depth of injury. Comparisons were also made between those arteries that remained dilated 1 month after balloon injury (LA ≥ 140%; n = 13) and those that renarrowed (LA ≤ 100%; n = 14).Results: For all 37 animals, LA 1 month after balloon injury correlated well with IELA (r = 0.72; p < 0.001) but not with IA (r = 0.10; p = 0.54), suggesting that changes in artery size rather than neointimal mass determined lumen caliber. When comparing arteries that remained dilated (n = 13) with those that renarrowed (n = 14), there were no differences in depth of wall injury (injury depth: 0, no injury; 1, intima; 2, IEL; 3, media; 4, EEL; 2.1 ± 0.3 vs 1.6 ± 0.3; p = 0.12), neointimal accumulation (IA, 507% ± 118% vs. 421% ± 81% of control; p = 0.55), or plaque burden (IA/IELA, 0.39 ± 0.04 vs 0.37 ± 0.06; p = 0.71), respectively. However, wall size defined as IELA was significantly smaller in arteries that renarrowed than in those that remained dilated (IELA, 115% ± 14% vs 230% ± 19% of control; p < 0.001).Conclusions: Restenosis after angioplasty has been attributed to intimal hyperplasia, equating loss of lumen caliber with neointimal mass. The data presented herein suggest that lumen narrowing after arterial wall injury may have little to do with intimal mass per se, but rather that a change in wall caliber or wall narrowing is the cause of restenosis. (J Vasc Surg 1997;26:875-83.)

Abstract Blood flow and the tractive force shear stress are important determinants of artery caliber, and reduced shear predisposes arteries to intimal thickening and atherosclerosis. The molecular basis for shear-induced changes in artery wall structure is poorly defined. A number of factors associated with normal and pathological artery wall remodeling are induced by shear stress in endothelial cell cultures. These include platelet-derived growth factor (PDGF), a potent mitogen, chemoattractant, and vasoconstrictor. To determine whether similar changes occur in vivo, we examined the effects of reduced blood flow on endothelial cell PDGF expression and proliferation in the rat carotid artery. Branches of the right internal and external carotid arteries were ligated, reducing common carotid artery blood flow from 8.0±0.6 to 0.5±0.1 mL/min while increasing flow in the left carotid from 7.1±0.6 to 10.8±0.7 mL/min. Shear stress following the procedure was 1.4±0.2 and 33.4±1.1 dyne/cm 2 in carotids with reduced blood flow (RF) and increased blood flow (IF), respectively. Arteries were harvested 6, 24, 48, or 72 hours after ligation, perfusion-fixed, and opened longitudinally. Endothelial cell proliferation (bromodeoxyuridine [BrdU] labeling) was assessed en face at 24, 48, and 72 hours; expression of mRNA for PDGF-A and -B chains and PDGF α- and β-receptors (in situ hybridization) was determined at 6, 48, and 72 hours after unilateral flow reduction. RF induced endothelial cell proliferation, which peaked at 48 hours (RF BrdU labeling: 24 hours, 0.4±0.2%; 48 hours, 7.2±2.0%; and 72 hours, 4.1±0.6%; n=5). PDGF-B expression increased in RF compared with IF endothelium within 48 hours and persisted at 72 hours (percent labeling [RF/IF×100]: 6 hours, 76±20%; 48 hours, 395±179%; and 72 hours, 208±44%; n=3). PDGF-A expression was similarly increased in RF endothelium. In contrast, expression of PDGF α- and β-receptors was undetectable in RF and IF endothelium at all times. We conclude that endothelial cell PDGF ligand expression is induced by reduced shear stress in vivo and may play an important role in flow-mediated remodeling and atherogenesis.

Purpose: This retrospective review examines the results of atherosclerotic renal artery (RA) repair in consecutive hypertensive African-Americans treated at our center and compares these results with Caucasians treated during the same period.Methods: From Jan. 1987 through Sep. 1996, a total of 485 patients underwent operative RA repair. Of these, 28 African-Americans and 370 Caucasians were managed for atherosclerotic renovascular disease. These cohorts were compared on the basis of preoperative blood pressure and renal function, extent of renal disease, extrarenal atherosclerosis, response to operation, and estimated survival.Results: The African-American cohort included nine men and 19 women (mean age, 62 years) with hypertension (mean blood pressure, 204 ± 31/109 ± 20 mm Hg) for an average of 10.2 ± 7.5 years. Ischemic nephropathy (serum creatinine level, >1.3 mg/dl) was present in 82% (n = 23) of the African-American group. RA reconstructions were unilateral in nine patients and bilateral in 19 patients (including repair to two solitary kidneys), for a total of 45 RA reconstructions (30 RA bypass procedures; eight transrenal/transaortic RA endarterectomy procedures; two RA reimplantations; five nephrectomies). Nine patients underwent combined aortic procedures (four abdominal aortic aneurysm; five occlusive disease). There was one perioperative death in the African-American group as a result of sepsis and multiple organ failure. Among surgical survivors, 20 African-American patients (74%) had a beneficial hypertension response (7% cured, 67% improved). Mean estimated glomerular filtration rate improved significantly from 34 to 42 ml/min/1.73 m2 (p < 0.001). In the 23 patients with ischemic nephropathy, 13 (57%) demonstrated greater than 20% decrease in serum creatinine level. In comparison with the 370 Caucasians (191 men, 179 women), the African-American cohort had significantly more preoperative heart disease (congestive heart failure or left ventricular hypertrophy; 68% vs 46%; p = 0.03) and tended toward more severe renal dysfunction (mean serum creatinine level, 2.5 vs 2.1 mg/dl; p = 0.25). However, African-Americans demonstrated a beneficial blood pressure and renal function response after operation, similar to Caucasians.Conclusions: Our results indicate that the majority of selected African-Americans have a favorable blood pressure and renal function response to operative renal artery repair. This beneficial clinical response appears equivalent to the response observed in Caucasian patients and supports the search for RA disease in hypertensive African-Americans.

Purpose To develop a simple method for determining the elastic behavior of vascular stents. Materials and Methods An experimental apparatus was constructed to determine the elastic behavior of four different vascular stents. Each stent was expanded within an artificial compliant vessel and was subjected to an increasing external pressure. The cross-sectional area of each stent was recorded at incremental changes in pressure. Compliance was estimated from the slope of a linear regression analysis fit to the pressure-area data in the elastic range of deformation. Results The self-expandable stents were the most compliant, and balloon-expandable stents exhibited the least compliance. The balloon-expandable stents initially deformed in an elastic manner and then yielded irrecoverably at higher pressures. Conclusion A simple method has been devised that allows the elastic behavior of stents to be assessed. Quantification of stent compliance with this method is important as a predictor of stent resistance to compression in vivo.

This review describes our experience with renal duplex sonography (RDS) in the elderly as a screening study for renovascular disease and as an intraoperative completion study to define technical error after operative renal artery repair. Methods of patient preparation, technical aspects of renal duplex interrogation and the comparison of RDS results with angiography in the elderly are presented in detail. In the hands of an experienced sonologist, RDS examination performed according to these methods and techniques correlates highly with angiography. We believe renal duplex sonography is the preferred screening test for main renal artery stenosis and occlusion in the elderly population.

This review summarizes our experience with the operative management of renovascular hypertension (RVH) in elderly patients (≥ 60 years of age). From 7/87 through 6/95,230 of 428 adult patients (54%) undergoing operation of renovascular hypertension at our center were in their seventh (153 patients), eighth (70 patients) or ninth (7 patients) decade of life (mean age: 68 years). There were 117 males and 113 females with blood pressures ranging from 280/190 to 178/90 (mean: 202/102 mmHg). One hundred and eighty patients (78%) had renal insufficiency (i.e., serum creatinine ≥ 1.3 mg/dl). One hundred and four patients (45 %) had severe insufficiency (i.e., serum creatinine ≥2.0 mg/dl), with 23 of these patients being dialysis dependent prior to operation. Two hundred and eighteen (95%) had evidence of organ specific atherosclerotic damage as manifested by cardiac disease (93%), cerebrovascular disease (38%) or renal insufficiency (78%). Operative management consisted of a unilateral procedure in 100 patients, bilateral procedures in 130 patients, including 26 nephrectomies. Simultaneous aortic replacement was performed in 95 patients (41%; 59 AAA and 36 occlusive disease). After surgery, there were 13 operative deaths (6%) and 13 renal artery repairs failed (4%). Hypertension was cured (9%) or improved (77%) in 86% of operative survivors. Renal function was improved in 43% and worsened in 15% of patients with nondialysis dependent renal insufficiency. Eighteen of twenty-three patients (78%) who were dialysis dependent before surgery were removed from dialysis following renal revascularization. On follow-up (mean: 29 months), we found that 28 patients died. Multivariate analysis demonstrated that preoperative congestive heart failure (p = 0.007) and increased serum creatinine (p = 0.001) were significant and independent predictors of death on follow-up. Estimated survival was significantly increased among patients with improved renal function after operation compared with patients unimproved. This review emphasizes the complexity of atherosclerosis in the elderly population presenting for operative management of renovascular hypertension. Despite the complexity of disease, our experience suggests that operative management is beneficial and can be accomplished with acceptable, albeit increased, risk in properly selected elderly patients. For elderly patients with renovascular disease in combination with renal insufficiency (i.e., ischemic nephropathy), improved renal function after operation may convey improved survival.

Purpose: This retrospective review describes current surgical management of renal artery (RA) fibromuscular dysplasia (FMD) to define contemporary clinical characteristics and surgical results in patients over the age of 21 years. Methods: From January 1987 through March 1994, 40 consecutive adults with hypertension had operative RA repair of FMD at our center and form the basis of this report. From histologic and angiographic appearance, FMD was classified with regard to specific type, noting the presence of RA dissections, RA macroaneurysms and branch RA involvement. Associations between blood pressure response to operation and patient age, duration of hypertension, presence of extrarenal atherosclerosis, presence of branch renal artery disease, and primary or secondary procedure were examined. Clinical characteristics and blood pressure response in these contemporary patients were compared with the results reported from an earlier surgical series. Results: Unilateral RA repair was performed in 34 patients, and bilateral procedures were required in six patients. Branch renal artery repair was performed in 28 instances, including ex vivo RA repair in 11 patients. There were no perioperative or follow-up deaths; however, three RA grafts (7%) failed within 30 days of operation. Initial blood pressure response was considered cured in 33%, improved in 57%, and failed in 10%. Analysis demonstrated that patients older than 45 years of age had a significantly decreased rate of hypertension cure compared with younger patients; among patients younger than 45 years of age, duration of hypertension was inversely related to cure. Compared with earlier surgical series, our current group of patients was significantly older, with more frequent branch renal artery involvement and extrarenal atherosclerosis, and demonstrated decreased rate of hypertension cure. Conclusion: A beneficial blood pressure response is currently observed in most selected patients after surgical correction of RA-FMD. Compared with earlier series, however, the present day patient differs in many respects, including a significantly decreased chance for hypertension cure after surgical repair. (J VASC SURG 1995;22:207-16.)

Purpose: This retrospective review describes surgical management of dialysis-dependent ischemic nephropathy. Methods: From February 1987 through September 1993, 340 patients underwent operative renal artery (RA) reconstruction at our center. A subgroup of 20 patients (6 women; 14 men; mean age 66 years) dependent on hemodialysis immediately before RA repair form the basis of this report. Glomerular filtration rates (EGFR) were estimated from at least three serum creatinine measurements obtained 26 weeks before and after operation. A linear regression model was used to estimate the mean rate of change of EGFR before and after RA repair. Comparative analysis of kidney status and change in EGFR were performed. The influence of function response on follow-up survival was determined by the product-limit method. Results: Hemodialysis was discontinued in 16 of 20 patients (80%). For these 16 patients, postoperative EGFR ranged from 9.0 to 56.1 ml/min/1.73 m 2 (mean 32.4 ml/min/1.73 m 2 ). Two of 16 patients resumed hemodialysis 4 and 6 months after surgery. Discontinuation of dialysis was more likely after bilateral or complete RA repair (15 of 16 patients) versus unilateral repair (one of four patients; p = 0.01). Permanent discontinuation of dialysis was associated with a rapid preoperative rate of decline in EGFR (mean slope log e EGFR: -0.1393 ± 0.0340 without dialysis; -0.0188 ± 0.0464 with dialysis; p = 0.04, but NS after controlling for multiple comparisons). Immediate increase in EGFR after operation was inversely correlated with the severity of nephrosclerosis (rank correlation: -0.57; 95% confidence interval [ -0.83, -0.10]). Follow-up death was associated with dialysis dependence; two deaths occurred among 14 patients not receiving dialysis, whereas five of six patients dependent on dialysis died ( p Conclusion: Surgical correction of ischemic nephropathy can retrieve renal function in selected patients dependent on dialysis characterized by a rapid decline in preoperative EGFR in combination with global renal ischemia treated by complete or bilateral renal revascularization. After RA repair, discontinuation of dialysis may be associated with improved survival rates when compared with continued dialysis dependence. (J VASC SURG 1995;21:197-211.)

Purpose: To define the value of renal duplex sonography (RDS) to detect the presence of critical renal artery (RA) stenosis or occlusion after surgical repair or percutaneous transluminal balloon angioplasty (PTRA), we retrospectively reviewed our recent 71-month experience. Methods: From January 1987 through November 1992, 272 patients underwent 279 operative RA repairs and 35 patients underwent PTRA. Three hundred twenty-five RDS examinations were performed in 176 patients after operative intervention or PTRA during the study period. Forty-one of these patients had conventional angiography providing 61 RA for RDS comparison, and these data form the basis of this analysis. Twenty-four women and 17 men (mean age 57 years) underwent 44 operative RA repairs or 17 PTRA for correction of atherosclerotic disease (51 arteries) or fibromuscular dysplasia (10 arteries). Before their renovascular procedure each patient had significant hypertension (mean 193/106 mm Hg). RDS after surgery or PTRA was technically complete for all 61 RA. Results: Compared with angiography RDS correctly identified 47 of 48 repairs with less than 60% RA stenosis, 7 of 11 repairs with 60% to 99% stenosis, and 2 renal artery occlusions, providing a 69% sensitivity rate, 98% specificity rate, 90% positive predictive value, and a 92% negative predictive value. These results were adversely affected by branch RA disease, which accounted for three of four false-negative RDS study results. For 50 kidneys undergoing correction of main RA disease, RDS demonstrated an 89% sensitivity rate, 98% specificity rate, and 96% overall accuracy. RDS results were equivalent for both surgical and PTRA treatment. Conclusions: From this experience we conclude that RDS is useful for anatomic evaluation after surgical RA repair or PTRA. A negative RDS result excludes stenosis or occlusion of a main RA reconstruction but does not exclude significant branch level disease. (J VASC SURG 1993;18:381-90.)

Objective This study evaluated the value of operation for treatment of all octogenarians with ruptured abdominal aortic aneurysms (AAA). Summary background data Elective AAA resection in octogenarians is safe, with published operative mortality rates of approximately 5%. Published operative mortality rates of ruptured AAA in this age group, however, vary from 27 to 92%. Methods To evaluate this question, we extracted the clinical course of the 34 octogenarians submitted to AAA resection by the authors from our total experience of 548 resections performed during the past 7 1/2 years. In this subgroup of octogenarians, 18 underwent elective AAA replacement, 5 were submitted to urgent resection of active but intact AAAs, and 11 had operations for ruptured AAAs. There were 23 males and 11 females in the group. The ages ranged from 80 to 91 years. Results Operative mortality in the patients managed electively was 5.6%. Two of the five patients (40%) submitted to operation for active yet unruptured aneurysms died in the preoperative period. Finally, 10 of the 11 patients (91%) with ruptured AAAs were operative mortalities. All of these operative mortalities in the ruptured AAA subgroup had severe hypotension preoperatively (mean systolic blood pressure: 23 mm Hg). The charges associated with the management of the ruptured AAA group averaged $84,486 (range $12,537-$199,233). Conclusions Although elective replacement of AAA in properly selected octogenarians appears valuable to prolong worthwhile life expectancy, this experience leads us to consider observation only in the treatment of octogenarians with ruptured AAA who present with severe hemodynamic instability.

To examine the treatment methods and early results of renovascular repair in our contemporary patient population, we reviewed our surgical experience during a recent 54-month period. From January 1987 to July 1991, 200 patients ranging in age from 5 to 80 years (mean, 56 years) were operated on for correction of nonatherosclerotic (43 patients) and atherosclerotic (157 patients) renovascular disease. The group included 92 men and 108 women, with blood pressures ranging from 300/198 mm Hg to 120/70 mm Hg (mean, 205/113 mm Hg). Defined by preoperative serum creatinine, 129 patients (65%) had evidence of renal insufficiency (Cr ≥ 1.3 mg/dl), whereas 71 patients (36%) had severe renal insufficiency (Cr > 2.0 mg/dl; 11 patients were dependent on dialysis). One hundred forty-seven patients with atherosclerotic renovascular disease (94%) demonstrated organ-specific atherosclerotic damage. Operative management of 291 kidneys included unilateral renal artery repair in 117 patients (58%), bilateral repair in 78 patients (39%), and primary nephrectomy in five patients (2.5%). Simultaneous aortic reconstruction was required in 64 patients (32%). There were five operative deaths (2.5% mortality rate) and four occluded renovascular repairs (1.4% primary failure) within 30 days of surgery. Hypertension was considered cured in 21% and improved in 70% of 195 operative survivors. In 70 patients with severe renal insufficiency before operation, estimated glomerular filtration rate was improved in 49% (8 of 11 patients removed from dialysis), unchanged in 36%, and worsened in 15%. Renal function response was significantly influenced by the site of disease and the operation. Twenty-six additional postoperative deaths occurred during follow-up (range, 6 to 58 months; mean, 24.4 months). Extreme atherosclerotic-renovascular disease, preoperative renal insufficiency, failure to improve renal function, and progression to dependence on dialysis after operation were associated with follow-up deaths. Although most patients had a beneficial outcome, failure to improve extreme renal insufficiency was associated with a rapid rate of death during a relatively short follow-up period. ( J Vasc Surg 1992; 16:319–31.)

To assess renal duplex sonography as an intraoperative study to detect technical defects during repair, 57 renal artery reconstructions in 35 patients were studied. Sixteen men and 19 women (mean age, 62 years) underwent unilateral (13 patients) or bilateral (22 patients) renal artery repair to 57 kidneys. Methods of repair included aortorenal bypass grafting in 29 cases (20 saphenous vein, 5 polytetrafluoroethylene, 4 Dacron), reimplantation in 7, transrenal thromboendarterectomy with patch angioplasty in 13, and transaortic extraction thromboendarterectomy in 8. Branch renal artery repair was required in six cases (five in vivo, one ex vivo). Fourteen patients had combined aortic replacement (11 patients: 8 abdominal aortic aneurysms, 3 aortic occlusions) or visceral artery reconstruction (three patients: three superior mesenteric artery thromboendarterectomies, one inferior mesenteric artery thromboendarterectomy). Intraoperative renal duplex sonography (mean scan time, 4.5 minutes) was complete in 56 of 57 repairs (98%), and renal duplex sonography was normal in 44 repairs (77%). Overall, B-scan defects were present in 13 repairs (23%). Six of these (11%) were defined as major B-scan defects by Doppler spectra with focal increases in peak systolic velocity ≥2.0 meters/sec (major defect, mean renal artery peak systolic velocity, 3.1 m/sec), which prompted immediate operative revision. Seven B-scan defects were defined as minor by Doppler spectra (minor defect, mean renal artery, peak systolic velocity, 0.7 m/sec) and were not revised. Postoperative evaluation (range, 1 to 22 months; mean follow-up, 12.4 months) of 55 renal artery repairs in 34 operative survivors (surface renal duplex sonography, 33 patients; renal angiography, 9 patients) demonstrated 42/43 renal artery repairs with normal intraoperative renal duplex sonography, and 6/6 repairs with minor B-scan defects were patent and free of critical stenosis. Of the 6 renal artery revisions prompted by major B-scan defects, 4 remained patent, 1 stenosed, and 1 occluded. Our experience suggests that intraoperative renal duplex sonography during renal artery repair provides valuable anatomic and physiologic information. Renal artery repairs with normal renal duplex sonography and minor B-scan defects without Doppler spectral changes demonstrated 98% patency without critical stenosis at 12.4 months of mean follow-up. However, major B-scan defects defined by a focal increase in renal artery peak systolic velocity should be considered for immediate correction. (J VASC SURG 1991;14:364-74.)

This retrospective review of data collected during a recent 42-month period from 58 consecutive patients with ischemic nephropathy submitted to operative management in the authors' center was undertaken to report the rate of decline in their renal function during the period before intervention and to examine the impact of operation on their outcome. Based on serum creatinine values, immediate preoperative estimated glomerular filtration rates (EGFR) ranged from 0 to 46 mL/minute (mean, 23.85 +/- 9.76 mL/minute). Eight patients were dialysis dependent or anuric at the time of operation. Patients with at least three sequential measurements for calculations of EGFR changes during the 6 months before operation (n = 50) and the first 12 months after operation (n = 32) were used to describe the preoperative rate of decline in EGFR and the impact of operation on this decrease in the operative survivors. In addition comparative analyses of data from patients with unilateral versus bilateral lesions and patients classified as having improvement in EGFR versus no improvement after operation were performed. Comparison of the immediate preoperative EGFR with the immediate postoperative EGFR for the entire group showed significant improvement in response to operation. Likewise the rate of deterioration in EGFR for the total group was improved after operation. A similar improvement in the rate of deterioration in EGFR was seen in the subgroup of patients who received an immediate improvement in EGFR in response to operation. These data argue that ischemic nephropathy is a rapidly progressive form of renal insufficiency. Although individual responses to operation were heterogeneous, renal revascularization may provide both immediate improvement in renal function and an improvement in its rate of deterioration during follow-up in patients with ischemic nephropathy.

With the exception of conventional angiography, no previously proposed screening test has the necessary sensitivity/specificity to guide further evaluation for correctable renovascular disease. Recently, renal duplex sonography has been suggested as a useful substitute in such screening for renovascular disease. This report analyzes our data collected over the past 10 months in evaluation of renal duplex sonography to examine its diagnostic value. The study population for renal duplex sonography validity analysis consisted of 74 consecutive patients who had 77 comparative renal duplex sonography and standard angiographic studies of the arterial anatomy to 148 kidneys. Renal duplex sonography results from six kidneys (4%) were considered inadequate for interpretation. This study population contained 26 patients (35%) with severe renal insufficiency (mean 3.6 mg/dl) and 67 hypertension (91%). Fourteen patients (19%) had 20 kidneys with multiple renal arteries. Bilateral disease was present in 22 of the 44 patients with significant renovascular disease. Renal duplex sonography correctly identified the presence of renovascular disease in 41 of 44 patients with angiographically proven lesions, and renovascular disease was not identified in any patient free of disease. When single renal arteries were present (122 kidneys), renal duplex sonography provided 93% sensitivity, 98% specificity, 98% positive predictive value, 94% negative predictive value, and an overall accuracy of 96%. These results were adversely affected when kidneys with multiple (polar) renal arteries were examined. Although the end diastolic ratio was inversely correlated with serum creatinine ( r = −0.3073, p = 0.009), low end diastolic ratio in 35 patients submitted to renovascular reconstruction did not preclude beneficial blood pressure or renal function response. We conclude from this analysis that renal duplex sonography can be a valuable screening test in the search for correctable renovascular disease causing global renal ischemia and secondary renal insufficiency (ischemic nephropathy). Renal duplex sonography does not, however, exclude polar vessel renovascular disease causing hypertension alone nor does it predict hypertension or renal function response after correction of renovascular disease. (J VASC SURG 1990;12:227-36.)

Atherosclerotic renovascular disease (RVD) is a suspected contributor to the morbidity and mortality of cardiovascular disease (CVD) through its potential effects on blood pressure and excretory renal function as well as through its associations with other forms of CVD. However, population-based data regarding the associations between the presence of RVD and prevalent CVD are lacking. The Cardiovascular Health Study (CHS) is a prospective, multicenter cohort study of CVD among elderly Americans. As part of an ancillary study, participants in the Forsyth County, North Carolina, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to establish the presence or absence of RVD (defined as any focal peak systolic velocity =1.8 m/second or the absence of a Doppler-shifted signal from an imaged artery). Demographic, risk factor, and prevalent CVD data were obtained from the CHS coordinating center and matched with ancillary study participants. Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African-Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 ±4.9 years underwent RDS examination. RVD was present in 57 participants (6.8%). Overall, clinical and/or subclinical manifestations of CVD were present in 603 participants (72.3%) at the time of RDS. Participants with RVD demonstrated a significantly greater prevalence of angina (p=0.002), previous myocardial infarction (p< 0.001), = 25% diameter-reducing internal carotid artery stenosis (p= 0.010), increased carotid intimal medial thickness (p= 0.003), and major electrocardiographic abnormalities (p= 0.013). Following adjustment for demographics and cardiovascular risk factors, the presence of RVD demonstrated a significant and independent association with prevalent coronary artery disease but not with prevalent cerebrovascular or lower extremity vascular disease. These results suggest important population-based associations between RVD and both clinical and subclinical manifestations of CVD, especially coronary artery disease.

Background: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS). Methods: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity ≥ 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination. Results: Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 ± 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72% versus 50%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16% versus 8%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure ( P = 0.034), clinical hypertension (odds ratio, 2.68; 95% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels ( P = 0.041). Conclusion: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.

The pathophysiological continuum that presumably begins with endothelial injury and dysfunction and ends with the fibronecrotic plaque, occlusive coronary artery disease, and diabetes-related nephropathy is potentially influenced by an association between hyper-glycemia, hypercholesterolemia and activation of the renin-angiotensin system. It is known that the resultant proliferative and progressive responses of the arterial wall in atherosclerosis and glomerulosclerosis are the culmination of the effects of a variety of mitogenic and inhibitory hormonal and trophic factors exerting their actions at stages that may be far removed both spatially and temporally from the initial injurious event. These processes are likely also at work in the diabetic kidney, but are not as well investigated. Regardless of the initiating mechanism, the vascular endothelium, inflammatory cell infiltration and the resultant tissue response have become the focus of attention in the pathogenesis of both atherosclerosis and diabetic nephropathy. A vast array of effects of angiotensin II likely to be mediated through both type 1 and type 2 angiotensin receptors are now described in the literature. Current data indicates that the role of angiotensin II in vascular remodeling and renal injury may originate from a local tissue source rather than the circulation. Regardless of its origin, angiotensin peptides and angiotensin receptors may contribute in significant ways to the atherogenic processes. While the stages of atherosclerosis and renal diabetic nephropathy in humans and animals are well defined morphologically, the mechanisms within vascular and renal tissues that contribute to these pathologies represent a spectrum of events occurring in different microenvironments over prolonged periods. This review describes well-established and novel aspects of angiotensin II-mediated actions as they relate to hypercholesterolemia-induced atherogenesis and diabetic nephropathy, and suggests potential pathways where angiotensin II might be substantially involved through the AT1 receptor in these processes, and thus may be blocked by AT1 receptor antagonists.

Vasopeptidase inhibition and Ang-(1-7) in the spontaneously hypertensive rat . Background Omapatrilat, a new vasopeptidase inhibitor, inhibits the activity of angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP). Because these two enzymes participate in the degradation of the vasodilator and natriuretic peptide, angiotensin-(1-7) [Ang-(1-7)], we assessed whether omapatrilat treatment is associated with changes in the plasma and urinary excretion rates of the angiotensins. Methods We investigated in spontaneously hypertensive rats (SHR) (0.24kg body weight) the effect of omapatrilat on plasma and urinary concentrations of angiotensin (Ang) I, Ang II and Ang-(1-7) during 17 days of administration of either the drug ( N = 15, 100 μmol/kg/day) or vehicle ( N = 14) in the drinking water. Hemodynamic and renal excretory function studies were associated with histological examination of the expression of Ang-(1-7) in the kidneys of both vehicle and omapatrilat-treated SHRs. Results Omapatrilat induced a sustained lowering of systolic blood pressure (-68mm Hg) without changes in cardiac rate. The mild positive water balance produced by omapatrilat did not cause natriuresis or kaliuresis, although it was associated with a significant decrease in urine osmolality. Blood pressure normalization was accompanied by increases in plasma Ang I (2969%), Ang II (57%), and Ang-(1-7) (163%) levels, paralleling pronounced increases in urinary excretion rates of Ang I and Ang-(1-7) but not Ang II. Detection of Ang-(1-7) immunostaining in the kidneys of five other SHR exposed either to vehicle ( N = 3) or omapatrilat ( N = 2) ascertained the source of the Ang-(1-7) found in the urine. Intense Ang-(1-7) staining, more pronounced in omapatrilat-treated SHR, was found in renal proximal tubules throughout the outer and inner regions of the renal cortex and the thick ascending loop of Henle, whereas no Ang-(1-7)-positive immunostaining was found in glomeruli and distal tubules. Conclusions Omapatrilat antihypertensive effects caused significant activation of the renin-angiotensin system associated with increases in urinary excretion rates of Ang I and Ang-(1-7). Combined studies of Ang-(1-7) metabolism in urine and immunohistochemical studies in the kidney revealed the existence of an intrarenal source, which may account for the pronounced increase in the excretion rate of the vasodilator heptapeptide. These findings provide further evidence for a contribution of Ang-(1-7) to the regulation of renal function and blood pressure.

This review describes the clinical outcome of surgical intervention for atherosclerotic renovascular disease in 500 consecutive patients with hypertension.From January 1987 to December 1999, 626 patients underwent operative renal artery (RA) repair at our center. A subgroup of 500 patients (254 women and 246 men; mean age, 65 plus minus 9 years) with hypertension (mean blood pressure, 200 plus minus 35/104 plus minus 21 mm Hg) and atherosclerotic RA disease forms the basis of this report. Hypertension response was determined from preoperative and postoperative blood pressure measurements and medication requirements. Change in renal function was determined with estimated glomerular filtration rates (EGFRs) calculated from serum creatinine levels. Proportional hazards regression models were used for the examination of associations between selected preoperative parameters, blood pressure and renal function response, and eventual dialysis-dependence or death.Two hundred three patients underwent unilateral RA procedures, 297 underwent bilateral RA procedures, and 205 patients underwent combined renal and aortic reconstruction. After surgery, there were 23 deaths (4.6%) in the hospital or within 30 days of surgery. Significant and independent predictors of perioperative death included advanced age (P.0001; hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.85 to 5.70) and clinical congestive heart failure (P =.013; HR, 3.05; 95% CI, 1.26 to 7.34). Among the patients who survived surgery, hypertension was considered cured in 12%, improved in 73%, and unchanged in 15%. For the entire group, renal function increased significantly after operation (preoperative versus postoperative mean EGFR, 41.1 plus minus 23.9 versus 48.2 plus minus 25.5 mL/min/m(2); P.0001). For individual patients, with a 20% or more change in EGFR considered significant, 43% had improved renal function (including 28 patients who were removed from dialysis-dependence), 47% had unchanged function, and 10% had worsened function. Preoperative renal insufficiency (P.001; HR, 2.35; 95% CI, 1.86 to 2.98), diabetes mellitus (P =.007; HR, 2.14; 95% CI, 1.15 to 3.97), prior stroke (P =.042; HR, 1.50; 95% CI, 1.02 to 2.22), and severe aortic occlusive disease (P =.003; HR, 1.69; 95% CI, 1.19 to 2.31) showed significant and independent associations with death or dialysis during the follow-up examination period. After operation, blood pressure cured (P =.014; HR, 0.52; 95% CI, 0.30 to 0.88) and improved renal function (P =.011; HR, 0.40; 95% CI, 0.19 to 0.81) showed significant and independent associations with improved dialysis-free survival rate. All categories of function response and time to death or dialysis showed significant interactions with preoperative EGFR.The surgical correction of atherosclerotic renovascular disease resulted in blood pressure benefit and retrieval of renal function in selected patients with hypertension. The patients with cured hypertension or improved EGFR after operation showed increased dialysis-free survival as compared with other patients who underwent surgery.

Abstract —Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of atherosclerosis in animal models and reinfarction rates after myocardial infarction in humans. Although expression of components of the renin-angiotensin system has been reported in human coronary arteries, no data regarding their presence in carotid arteries, a frequent site for the occurrence of atherosclerosis plaques, are available. The following study sought to determine whether ACE mRNA and protein can be detected in human carotid atheromatous lesions. Twenty-four intact endarterectomy specimens were obtained from patients with severe carotid occlusive disease (17 males and 7 females, aged 68±1 years) and fixed within 30 minutes. Carotid artery specimens contained advanced Stary type V and VI lesions, and human ACE mRNA expression and protein were localized in cross sections by the combination of in situ hybridization and immunohistochemistry. Cell type–specific antibodies were used to colocalize ACE to smooth muscle cells, endothelial cells, macrophages, or lymphocytes. ACE protein was localized in the intima, whereas the overlying media was largely free of ACE staining. In less complicated lesions, ACE staining was modest and could be visualized in scattered clusters of macrophages and on the luminal side of carotid artery vascular endothelium. Smooth muscle cells were largely negative. ACE staining increased as lesions became more complex and was most prominent in macrophage-rich regions. The shoulder regions of plaques contained numerous ACE-positive macrophage foam cells and lymphocytes. In these areas, microvessels were positive for endothelial cell and smooth muscle cell ACE expression. However, microvessels in plaques free of inflammatory cells were stained only faintly for ACE expression. Labeling for ACE mRNA mirrored the pattern of protein expression, localizing ACE mRNA to macrophages and microvessels within the intima. In conclusion, atherosclerosis alters carotid artery ACE production, increasing transcription and translation within regions of plaque inflammation. These data provide another important mechanism by which inflammation associated with increased ACE expression may contribute to the progression of atherosclerosis.

Objectives: To determine (1) if perioperative use of esmolol in major vascular surgery patients provides strict heart rate (HR) control, (2) what doses of esmolol are required to do this, and (3) does this control influence myocardial ischemia or result in adverse consequences. Design: Prospective study of 40 patients randomized to two groups: The HR was controlled to either less than 80 beats/min (group 80) or less than 110 beats/min (group 110) using esmolol. Patients were monitored continuously for electrocardiographic changes perioperatively. HR control began after induction of anesthesia and continued for 48 hours thereafter. Setting: Operating room and intensive care unit. Patients: Patients undergoing abdominal vascular surgery involving aortic cross-clamping. Interventions: Esmolol was titrated until the target HR was met. Measurements and Results: Only one patient demonstrated an adverse effect. The median infusion rates were 100 and 12.5 μg/kg/min for groups 80 and 110. Target HR was met less in group 80 than in group 110, primarily in the postoperative period. Ischemia patterns were not significantly different between groups. Conclusion: Using esmolol for HR control in the intraoperative period for abdominal vascular surgery patients is effective and safe. HR control was much less effective in the postoperative period, but esmolol is safe when used at recommended doses. Further study with a larger number of patients is necessary to determine whether strict HR control with esmolol affects the incidence of myocardial ischemia or infarction in this patient population.

Accumulating evidence suggests that angiotensin-(1-7) is an important component of the renin-angiotensin system, having actions that are either identical to or opposite that of angiotensin II. Angiotensin I can be directly converted to angiotensin-(1-7), bypassing formation of angiotensin II. This pathway is under the control of three enzymes: neutral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptidase 24.26. Two of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to the breakdown of bradykinin and the atrial natriuretic peptide. Furthermore, angiotensin-(1-7) is a major substrate for angiotensin-converting enzyme. These observations suggest that the process of biotransformation between the various Ang peptides of the renin-angiotensin system and other vasodepressor peptides are intertwined through this enzymatic pathway. Substantial evidence suggests that angiotensin-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, and nitric oxide, while also augmenting the metabolic actions of bradykinin. In addition, angiotensin-(1-7) alters tubular sodium and bicarbonate reabsorption, decreases Na+-K+-ATPase activity, induces diuresis, and exerts a vasodilator effect. These physiologic effects of angiotensin-(1-7) favor a blood pressure-lowering effect. The majority of the data currently available suggest that angiotensin-(1-7) mediates its effects through a novel non-AT1/AT2 receptor subtype.

A total of 31 healthy volunteers [39 +/- 7 (SD) years] and 18 untreated essential hypertensive subjects [43 +/- 9 years] collected urine for 24 h after a physical examination and laboratory tests. Radioimmunoassay measurements of angiotensin-(1-7) [Ang-(1-7)] in urine and plasma were done as described previously. Sitting systolic and diastolic blood pressures (+/- SD) averaged 118 +/- 11/74 +/- 7 mm Hg and 146 +/- 16/96 +/- 8 mm Hg in normal and essential hypertensive subjects, respectively (P.001), whereas 24 h urinary volume was not different in normal and essential hypertensive subjects (P.05). The concentration of Ang-(1-7) in the urine of normal subjects averaged 62.6 +/- 22.6 pmol/L corresponding to a urinary excretion rate of 98.9 +/- 44.7 pmol/24 h. Concurrent measurements of plasma Ang-(1-7) showed that the content of Ang-(1-7) in urine was 2.5-fold higher than that measured in the plasma. In contrast, untreated essential hypertensive subjects had lower concentrations and 24 h urinary excretion rates of Ang-(1-7) averaging 39.4 +/- 18.0 pmol/L and 60.2 +/- 14.6 pmol/24 h, respectively, (P.001). Differences in the excretory rate of Ang-(1-7) between normal volunteers and essential hypertensive subjects were not modified by normalization of the data by urinary creatinine excretion rates. Urinary concentrations of Ang-(1-7) correlated inversely with systolic, diastolic and mean arterial pressures (r = -0.48, P.001). Both urinary Ang-(1-7) [odds ratio of 0.92 (95% CI: 0.88-0.97)] and age were independent predictors of systolic blood pressure. These studies demonstrated the presence of Ang-(1-7) in urine and the existence of reduced levels of the heptapeptide in individuals with untreated essential hypertension. The relatively higher concentrations of Ang-(1-7) in urine compared to plasma agrees with data that showed that Ang-(1-7) may contribute to the regulation of blood pressure. The inverse association between Ang-(1-7) and arterial pressure provides a potential marker for the characterization of forms of essential hypertension associated with reduced production or activity of vasodilator hormones.

Transgenic [(mRen-2)27] rats develop severe hypertension as the result of transfection with the mouse Ren-2 gene. This study tested the hypothesis that hypertensive [(mRen-2)27] rats have increased endothelial dysfunction by examining the extent of vascular endothelial cell injury and turnover within the thoracic aorta of age-matched female transgene positive [Tg(+)] and transgene negative [Tg(-)] littermates. Transgenic hypertensive rats had arterial pressures significantly higher than Tg(-) animals, but no differences in heart rate or body weight. The extent of endothelial cell injury was estimated in Haütchen preparations of thoracic aorta endothelium by counting cells immunostained for the presence of cytoplasmic immunoglobulin G (IgG) at sites with or without intercostal artery branches. Both Tg(+) and Tg(-) littermates had a greater percentage of injured endothelial cells at branch sites than at nonbranch aorta (P.01). However, the number of vascular endothelial cells staining positively for IgG was significantly higher in hypertensive rats both at sites away from (P.05) and in the immediate vicinity of (P.1) the orifices of intercostal arteries. En face preparations of the thoracic aorta were also examined for cells incorporating 5-bromo-2 '-deoxyuridine (BrdU) to estimate the percentage of endothelial cells undergoing replication. There was no difference in endothelial cell replication at either branch or nonbranch sites between hypertensive and normotensive rats. However, the percentage of endothelial cells undergoing replication at branch sites in both Tg(+) and Tg(-) rats was significantly greater than at nonbranch sites (P.01). These data provide the first demonstration for the effects of high blood pressure on the vascular endothelium of a monogenetic model of hypertension produced by increased activity of the renin-angiotensin system. The divergent effects of this form of hypertension on vascular endothelial injury and endothelial turnover suggest that the decrease in the reparative capacity of the vascular endothelium induced by the combination of hypertension and associated angiotensinemia may contribute to the endothelial dysfunction accompanying vascular remodeling.

Purpose To compare the in vivo response to a new mechanically expandable vascular stent with the response to an existing type of balloon-expandable stent. Materials and Methods Prototype stents were deployed by means of a balloon catheter in the left iliac arteries of four healthy dogs. Palmaz stents were deployed in the contralateral iliac arteries to act as a control, and all stents were explanted after 6 weeks. Arteriography was performed at the time of insertion and before harvest, and pressure gradients were measured across each stent. The stents were then harvested and submitted for histologic examination. Results The performance of the prototype stent was similar to that of the Palmaz stent with respect to structural integrity, migration, maintenance of intraluminal diameter, ease of deployment, radiopacity, and pressure gradients. Unlike the Palmaz stent, the prototype stent did not foreshorten during expansion. The stents showed a lack of uniformity in terms of the measured luminal area and neointimal accumulation. Neointimal accumulation was more confined to the struts of the prototype stent; the lumen therefore had a fluted appearance. Neointimal accumulation was more broadly distributed around the circumference of the vessel wall of the Palmaz stent. Conclusion In vivo performance of the prototype stent was similar to that of the Palmaz stent. Stent geometry may be an important determinant of neointimal response and resultant long-term patency.

Purpose This retrospective study examines results with simultaneous aortic and renal artery repair in 133 consecutive hypertensive patients. These results are compared with consecutive patient groups undergoing aortic reconstruction alone (269 patients) or renal artery reconstruction alone (182 patients). Methods From January 1987 through July 1995, 61 women and 72 men (mean age, 62.5 years) underwent combined repair of renal artery and aortic disease (abdominal aortic aneurysm [AAA] : 47 patients ; occlusive disease : 86 patients ; both : 12 patients). All patients were hypertensive (mean blood pressure : 194/103 mmHg ; mean medications : 2.4). Evidenced by serum creatinine levels ≥ 2.0 mg/dL, 46 patients (35%) had significant renal dysfunction (mean serum creatinine level : 3.78 mg/dL ; range, 2.0-10.6 mg/dL, including 7 dialysis-dependent patients). Aortic replacements (29% tube grafts ; 71% bifurcated grafts) were combined with unilateral renal artery repair in 47% of patients ; 53% had bilateral repair. Preoperative clinical features and perioperative mortality were compared with those groups having isolated aortic and renal repairs. Results There were seven perioperative deaths (5.3%) after combined repair, which differed significantly from isolated aortic repair (mortality : 0.74% ; p = 0.005), but did not reach statistical significance when compared with the isolated renal artery group (mortality : 1.65% ; p = 0.145). Risk analysis did not reveal a significant association between preoperative clinical features and mortality in either the combined repair group or the groups undergoing renal repair alone or aortic repair alone. Among survivors in the combined group, a favorable hypertension response was observed in 63%. This differed significantly from the group receiving renal repair alone (90% cured/improved; p < 0.001). Based on a 20% decrease in serum creatinine levels, excretory renal function was improved in 33% of patients with combined repair, including four of the seven patients removed from hemodialysis. There were eight late deaths in the combined group. Conclusions Our experience suggests that contemporary perioperative mortality for combined aortic and renal repair has improved compared with earlier reports ; however, perioperative mortality for simultaneous reconstruction remains greater than repair of aortic disease alone. Moreover, a lower rate of favorable hypertension response was observed after combined correction compared with renal artery repair alone. These differences suggest that aortic and renal artery repair should only be combined for clinical indications rather than for prophylactic repair of clinically silent disease.

Transgenic rats carrying the mouse Ren-2 gene (Ren-2d)27 provide a unique model to study the interplay between the renin-angiotensin system and estrogen in the pathogenesis of hypertension. In this study we measured the effects of ovariectomy and estrogen replacement on blood pressure and the contribution of vascular endothelium relaxing factor, nitric oxide, in female transgenic hypertensive rats and normotensive Sprague-Dawley (SD) rats. Both groups of animals were either ovariectomized or sham-operated at 12 weeks of age. Ovariectomized rats were treated with either 17 beta-estradiol (70 micrograms/day) or placebo for 4 weeks, whereas sham-operated rats received placebo alone. Mean arterial blood pressure measured in conscious rats directly by an arterial catheter was significantly higher in ovariectomized rats, compared with ovariectomized rats given estrogen replacement therapy for both transgenic (167 +/- 5 v 154 +/- 4 mm Hg, P < .05) and SD rats (125 +/- 4 v 113 +/- 5 mm Hg, P < .05). The contribution of endothelium-derived nitric oxide to the maintenance of blood pressure was examined by acute systemic injection of NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg). L-NMMA caused a significantly greater increase in blood pressure in sham-operated transgenic as compared to SD rats (34 +/- 3 v 14 +/- 3 mm Hg, P < .05). The response in ovariectomized transgenic rats was markedly reduced (13 +/- 3 mm Hg), reaching levels that were no different from sham-operated SD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The surgical management of chronic atherosclerotic renal artery occlusion (RA-OCC) was studied.From January 1987 through December 1996, 397 consecutive patients were treated for atherosclerotic renal artery disease. Ninety-five hypertensive patients (mean blood pressure, 204 +/- 31/106 +/- 20 mm Hg; mean medications, 3.0 +/- 1.1 drugs) were treated for 100 RA-OCCs. Eighty-four (88%) patients had renal dysfunction, defined by serum creatinine levels/=1.3 mg/dL (mean serum creatinine level, 2.8 +/- 2.0 mg/dL). Demographic characteristics, operative morbidity and mortality, blood pressure/renal function response, and postoperative decline in renal function were examined and compared with that of 302 patients treated for renal artery stenosis (RAS).After operation, there were 5 perioperative deaths (5.2%), 2 (2.8%) after revascularization and 3 (12%) after nephrectomy (P =.11), compared with 12 (4.0%) perioperative deaths in the RAS group (P =.59). After controlling for important covariates, estimated survival and blood pressure benefits did not differ between RA-OCC patients treated by nephrectomy or revascularization (P =.13; 87% vs 92%, P =.54). Excretory renal function was considered improved in 49% of 79 RA-OCC patients with renal dysfunction, including 9 patients removed from dialysis-dependence. Among patients treated for unilateral disease, revascularization for RA-OCC was associated with significant improvement in renal function (P.01); however, nephrectomy alone did not increase renal function significantly. Improved renal function after operation was associated with a significant and independent increase in survival (P.01) and dialysis-free survival (P.01) among patients treated for RA-OCC. In addition, blood pressure benefit, renal function response, and estimated survival did not differ significantly after reconstruction for RA-OCC or RAS.Among hypertensive patients treated for RA-OCC, equivalent beneficial blood pressure response was observed after both revascularization and nephrectomy. In patients who underwent bilateral renal artery revascularization, the change in excretory renal function attributable to repair of RA-OCC cannot be defined. In patients treated for unilateral disease, however, improvement in function was observed only after revascularization. Moreover, improved renal function demonstrated a significant and independent association with improved survival. This experience supports renal revascularization in preference to nephrectomy for RA-OCC in select hypertensive patients when a normal distal artery is demonstrated at operation.

Background Renovascular disease is a cause of secondary hypertension and renal insufficiency and is suspected to contribute to morbidity and mortality of coronary heart disease. This investigation prospectively examined associations between renovascular disease and adverse coronary events among a population-based sample of elderly Americans. Methods The Cardiovascular Health Study is a prospective, multicenter cohort study of cardiovascular disease risk factors, morbidity, and mortality among Americans older than 65 years. Renal duplex sonography was performed on 870 individuals between January 1995 and February 1997. Renovascular disease was defined as any focal peak systolic velocity of 1.8 m/s or greater (renal artery stenosis) or the absence of a Doppler-shifted signal from an imaged artery (renal artery occlusion). Adverse coronary events were defined as hospitalized angina, fatal or nonfatal myocardial infarction, and coronary revascularization. Results During a mean follow-up of 14 months, 68 participants experienced incident or recurrent adverse coronary events. The presence of renovascular disease demonstrated a significant relationship with adverse coronary events (hazard ratio, 1.96; 95% confidence interval, 1.00-3.83; P = .05) that remained after controlling for the effects of coexisting atherosclerotic risk factors and prevalent cardiovascular disease. The relationship between renovascular disease and adverse coronary events was not dependent on the effects of increased blood pressure. Conclusions The presence of renovascular disease was associated with an increase in the risk of adverse coronary events in this sample. The increment in risk was not dependent on the effects of associated atherosclerotic risk factors, other prevalent cardiovascular disease, or increased blood pressure.