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U74389F is a compound in a family of 21-aminosteroids devoid of classical glucocorticoid action that inhibit lipid peroxidation. These compounds improve neurologic function and tissue survival after head or spinal cord injury. Dexamethasone inhibits development of intimal hyperplasia (IH) and improves attenuated nitric oxide (NO) production of the rabbit aorta subsequent to balloon catheter injury. We tested the hypothesis that U74389F is protective in a catheter-induced endothelial-denuded and arterial injury model. A 4-Fr Fogarty balloon (BALL) embolectomy catheter was passed through the thoracic aorta of New Zealand White rabbits treated with 15 mg/kg U74389F (LAZ) 2 days before and 1 week after injury. Animals were killed at 4 weeks after surgical intervention, and formation of IH was determined by calculating the intimal/medial ratio (I/M). The treatment groups of animals were injured untreated (BALL), injured treated (BALL/LAZ), uninjured treated (CONTROL/LAZ), and sham-operated treated (SHAM/LAZ). Scanning electron microscopy revealed that after injury lazaroid treatment produced an improvement of the neoendothelium (alignment in the direction of blood and fewer intercellular gaps) as compared with injured but untreated aortas. Relaxation to acetylcholine (NO formation) was impaired in aortic rings from catheterized animals; lazaroid treatment improved the relaxation to 10–6 mol/L acetylcholine but not to lower concentrations. I/M for SHAM/LAZ, BALL, and BALL/LAZ was 0.02 ± 0.02, 21.6 ± 1.6, and 17.2 ± 2.5, respectively; BALL vs. BALL/LAZ, p < 0.06. An increased contractile response to 120 mmol/L KCl was observed after lazaroid treatment. This is the first report of lazaroid-mediated improvement in the neoendothelial morphology, improved neoendothelial NO generation, and augmented hypopolarizing contractile response, but no attenuation in the development of IH.

OBJECTIVE—Flow-mediated dilatation (FMD), induced by occlusion of the brachial artery, is an index of nitric oxide-dependent endothelial function that is impaired in patients with type 2 diabetes. Sildenafil (Viagra) is an inhibitor of phosphodiesterase 5 (PDE-5), which is used for management of erectile dysfunction in a broad range of patients, including those with type 2 diabetes. Its effects on endothelial function in these patients have not been previously assessed.RESEARCH DESIGN AND METHODS—We assessed the acute and prolonged effects of a low dose of sildenafil (25 mg) on FMD in patients with type 2 diabetes. We performed a double-blind, placebo-controlled cross-over trial in 16 patients (14 of whom completed the study) with type 2 diabetes who had erectile dysfunction without overt clinical heart disease.RESULTS—In these patients, the mean ± SD brachial artery diameter (BAD) measured by ultrasound was 4.33 ± 0.6 mm. After inducing FMD, the BAD increased 8% to 4.66 ± 0.6 mm (P = 0.2). One hour after oral administration of sildenafil 25 mg, FMD increased the BAD significantly by 15% to 4.99 ± 0.5 mm (P ≤ 0.01), whereas it did not change with placebo (4.6 ± 0.6 mm, P = 0.1). After treatment with sildenafil 25 mg daily for 2 weeks and testing 24 h after the last dose, the mean FMD was 14% (P = 0.01). In contrast, the mean FMD with placebo was 9% (P = 0.45).CONCLUSIONS—We conclude that acute and prolonged sildenafil treatment has a favorable effect on brachial artery flow-mediated dilatation that persists for at least 24 h after the last dose. Further investigation is needed to determine whether this prolonged effect has clinical implications in patients with type 2 diabetes.

Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 μg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area × 100; p < 0.05) but had no effect at lower (5 μg/kg/day) or higher (20 μg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p < 0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function.

Neointimal thickening after catheter injury has been reported to be influenced by the integrity of the vascular endothelium. We have previously shown that neointimal thickening is significantly reduced in alloxan-induced diabetic New Zealand White rabbits after catheter injury compared with euglycemic rabbits. In the present study, it was hypothesized that endothelial cell regrowth, morphology, and endothelium-dependent vasoreactivity after catheter injury are improved in the diabetic rabbit (glucose ≥400 mg/dl) compared with the euglycemic rabbit. Two weeks after catheter injury, the percent endothelial regrowth was significantly increased in diabetic animals compared with euglycemic animals (32.1 ± 2 and 15.6 ± 1, respectively; P < 0.05). The endothelial cell morphology analyzed by scanning electron microscopy was also restored 2 wk after catheter injury in thoracic aortas from the diabetic animals compared with vessels from euglycemic animals. Endothelium-dependent relaxation to ACh in vessels from diabetic and euglycemic rabbits was attenuated 2 wk after injury, and, although improved by 4 and 8 wk, relaxation remained significantly depressed. These results suggest that endothelial cell regrowth and morphology in diabetic animals was improved compared with euglycemic animals; however, endothelium-dependent vasoreactivity remained impaired. Thus the attenuated neointimal thickening seen in the diabetic rabbit may be a function of the rate and degree of regrowth rather than the normalization of ACh-induced relaxation.

We report the occurrence of acute heparin-induced thrombocytopenia in a patient with anaphylaxis that began immediately after an intravenous bolus dose of unfractionated heparin. This case report is the first to document the concurrence of these 2 reactions to heparin. An abrupt fall in platelet count was documented immediately after the anaphylactic response. Study results for antibodies characteristic of heparin-induced thrombocytopenia were positive in 2 assays: serotonin release assay and heparin platelet factor 4 enzyme-linked immunosorbent assay. The patient's antibody was exclusively immunoglobulin G. Any explanation for the relationship between the antibody response observed and the histamine release remains speculative. (J Vasc Surg 1998;28:561-5)

Patients presenting with critical limb ischemia following failed infrainguinal grafts have been reported to have a significant amputation rate and reduced long-term survival. The authors reviewed their three-year experience with 33 patients with failed infrainguinal reconstruction. The median age was 63.1 years of age (range forty-three to eighty-seven years). There were 19 women and 14 men. Risk factors included the following: hypertension 31 (94%), diabetes 21 (64%), and tobacco use 30 (91%). All patients had limbthreatening ischemia,15.had gangrene (45.4%),8.had ulceration (24.2%), and 10 had rest pain 10 (30.3%). There had been 42 previous revascularizations (1.27 per patient, range 1 to 6). The authors performed 45 revascularization operations (1.36 per patient, range 1 to 4). Inflow was as follows: common femoral artery in 29 (64.4%), superficial femoral artery in 9 (20%), profunda femoris in 4 (8.9%), aortobifemoral graft limb in 2 (4.4%), and femoral-femoral bypass graft in 1 (2.2%). Outflow was as follows: posterior tibial artery 12 (26.7%), peroneal artery in 17 (37.8%), anterior tibial artery in 7 (15.6%), popliteal artery in 5 (11.1%), and tibioperoneal trunk in 4 (8.9%). The conduits were as follows: great saphenous vein (GSV) from the opposite lower limb in 8 (17.8%), GSV/lesser saphenous vein (LSV) composites in 8 (17.8%), expanded polytetrafluoroethylene in (ePTFE) 5 (11.1%), LSV composite in 10 (22.2%), ePTFE/GSV composite in 5 (11.1%), cadaveric vein in 2 (4.4%), superficial femoral vein/ePTFE composite in 2 (4.4%), endarterectomized superficial femoral artery/GSV composite in 1 (2.2%), GSV/upper limb vein composite in 1 (2.2%); and upper limb vein in 3 (6.7%). There was one perioperative death (2.2%). Six patients died during the follow-up period (74.1% survival). Limb salvage was obtained in 28 patients (83.1%). Cumulative secondary patency was 73.2% at three years. These results indicate that: (1) aggressive revascularization for failed infrainguinal grafts can result in significant limb salvage, and (2) long-term survival is common in this patient population.

Purpose: Synthetic vascular grafts have never achieved long-term patency comparable to autologous saphenous vein. Changes in graft wall porosity and carbon coating of the luminal surface have both been suggested to improve patency. Methods: Forty-two mongrel dogs, weighing 20 to 30 kg, underwent bilateral aortoiliac grafting with one of three randomly selected grafts: group I, 60 μm carbon-coated, thin-walled expanded polytetrafluoroethylene (ePTFE); group II, 60 μm thin-walled uncoated ePTFE; or group III, regular ePTFE. All grafts were 10 cm long and had an internal diameter of 5 mm. Twenty-one dogs were killed at 60 days and 21 dogs were killed at 120 days. Thus in each group there were 14 60 μm, thin-walled, carbon-coated ePTFE grafts; 14 60 μm, thin-walled, uncoated ePTFE grafts; and 14 regular ePTFE grafts. Results: At 60 days, 12 (85.7%) of 14 group I, 13 (92.3%) of 14 group II, and 9 (64%) of 14 group III grafts were patent. At 120 days, 12 (85.7%) of 14 group I, II (78.6%) of 14 group II, and 6 (42.9%) of 14 group III grafts were patent. The patency of the 60 μm carbon-coated, thin-walled ePTFE at 120 days was significantly improved compared with that of the regular ePTFE ( p ≤ 0.05). The patency of the 60 μm thin-walled uncoated ePTFE was improved relative to conventional ePTFE at 120 days, although this difference was not statistically significant. There was no significant difference in patency between 60 μm carbon-coated, thin-walled ePTFE and 60 μm thin-walled uncoated ePTFE. When the results were analyzed simply on the basis of graft porosity, the 60 μm porosity grafts had a significantly improved patency compared to the regular ePTFE at 120 days ( p ≤ 0.05). Histologically, the 60 μm porosity grafts had significantly better tissue ingrowth along their entire length, regardless of the presence or absence of carbon coating. This ingrowth was present at both 60 days and 120 days. Conclusions: Our data suggest that increasing ePTFE graft porosity to 60 μm improves overall patency. However, the addition of carbon lining did not appear to further augment patency. (J. VASC SURG 1993;18:10-5.)

U74389F is a compound in a family of 21-aminosteroids devoid of classical glucocorticoid action that inhibit lipid peroxidation. These compounds improve neurologic function and tissue survival after head or spinal cord injury. Dexamethasone inhibits development of intimal hyperplasia (IH) and improves attenuated nitric oxide (NO) production of the rabbit aorta subsequent to balloon catheter injury. We tested the hypothesis that U74389F is protective in a catheter-induced endothelial-denuded and arterial injury model. A 4-Fr Fogarty balloon (BALL) embolectomy catheter was passed through the thoracic aorta of New Zealand White rabbits treated with 15 mg/kg U74389F (LAZ) 2 days before and 1 week after injury. Animals were killed at 4 weeks after surgical intervention, and formation of IH was determined by calculating the intimal/medial ratio (I/M). The treatment groups of animals were injured untreated (BALL), injured treated (BALL/LAZ), uninjured treated (CONTROL/LAZ), and sham-operated treated (SHAM/LAZ). Scanning electron microscopy revealed that after injury lazaroid treatment produced an improvement of the neoendothelium (alignment in the direction of blood and fewer intercellular gaps) as compared with injured but untreated aortas. Relaxation to acetylcholine (NO formation) was impaired in aortic rings from catheterized animals; lazaroid treatment improved the relaxation to 10-6 mol/L acetylcholine but not to lower concentrations. I/M for SHAM/LAZ, BALL, and BALL/LAZ was 0.02 +/- 0.02, 21.6 +/- 1.6, and 17.2 +/- 2.5, respectively; BALL vs. BALL/LAZ, p0.06. An increased contractile response to 120 mmol/L KCl was observed after lazaroid treatment. This is the first report of lazaroid-mediated improvement in the neoendothelial morphology, improved neoendothelial NO generation, and augmented hypopolarizing contractile response, but no attenuation in the development of IH.

Management of patients after operative repair of abdominal aortic aneurysms can be further complicated if primary closure of the abdominal wall cannot be technically accomplished or is associated with profound increases in intraabdominal and peak inspiratory pressures. We recently treated five patients with ruptured abdominal aortic aneurysms and one patient with a ruptured thoracoabdominal aneurysm whose abdominal incisions had to be closed with a Dacron reinforced, silicone sheet. All patients were hemodynamically unstable either at admission to the hospital or became so during operation. Four patients required the insertion of a silicone rubber sheet at the primary operation because of massive retroperitoneal hematoma or edema of the bowel wall or both. Incisions in two patients were closed primarily, but the patients required reexploration and secondary closure with silicone rubber sheets because of the development of marked increases in peak inspiratory pressures, intraabdominal pressures, and decreased urinary output. Four of the six patients subsequently underwent successful removal of the silicone rubber sheets with delayed primary closure of the abdominal wall, and two others died before removal. The patient with the ruptured thoracoabdominal aneurysm died on postoperative day 20 because of pulmonary sepsis but had a healed abdominal incision. The three surviving patients have been discharged. A silicone rubber sheet may be necessary for closure of the abdominal wall after repair of ruptured abdominal aortic aneurysm in patients where primary abdominal wall closure is impossible or where it results in compromise in respiratory or renal function.

A 35-year-old black woman presented with thrombosis of an anomalous right subclavian artery and distal arterial embolization. Initially, her right subclavian artery was reimplanted onto the common carotid artery, and a brachial artery embolectomy plus intraoperative thrombolytic therapy were used to reopen her distal arterial circulation. When her brachial artery repair thrombosed the following day, a distal ulnar artery bypass and repeat thrombolytic therapy were required to restore arterial patency. Six months later, she returned with severe, progressive, neointimal hyperplasia of her brachial artery and a second attempt at arterial reconstruction was unsuccessful. She eventually required a right below-elbow amputation. This patient demonstrated an anomalous right subclavian artery that presented with distal embolization without an antecedent history of severe atherosclerotic disease or the development of a right subclavian artery aneurysm. A review of the medical literature relating to complications of this anomaly is provided.

The primary aim of this study was to evaluate the effect of pioglitazone on endothelial function, as assessed by flow-mediated dilatation (FMD) nitroglycerine-induced dilatation (NID) in patients with type 2 diabetes mellitus treated with insulin. A randomized double-blind placebo-controlled trial involved 20 patients with insulin-treated type 2 diabetes. Patients received either pioglitazone 30 mg or placebo for 4 months. FMD, NID, and HbA1c were measured before and after 4 months of treatment. HbA1c decreased from 10.0 (+/- 2.3) to 8.4 (+/- 2.0) in the pioglitazone group, a statistically significant improvement in glycemic control (p = 0.018). HbA1c was unchanged in the placebo group (p = 0.477). Endothelial function as assessed by FMD significantly improved from 10.1 (+/- 4.0)% to 14.6 (+/- 6.2)% in the pioglitazone group (p = 0.036) as compared to the placebo group (p = 0.705). There was a trend towards improvement in the NID in the pioglitazone group (from 13.3 +/- 8.0% to 18.9 +/- 5.4%; p = 0.056). In insulin-treated patients with type 2 diabetes, the addition of pioglitazone improves endothelial function, as measured by FMD. Addition of pioglitazone to insulin in type 2 diabetes patients may favorably impact vascular function in diabetes, even after many years of insulin resistance and hyperglycemia.

Should one consider a primary above-the-knee (AK) amputation ignoring the benefits of rehabilitation of a below-the-knee (BK) amputation if there is a chance the BK amputation may fail? This is a retrospective study of 112 patients (42% women, 58% men) with an average age of fifty-seven years who under went conversion of a BK to AK amputation. A total of 3,731 BK amputations were performed during the same time period; thus 3% of the total required revisions. Of 29 deaths, 17 patients died of myocardial infarction and 7 second ary to cerebrovascular accident. Of the patients who died, 59% had diabetes and 100% had heart disease: 100% of the patients who died with cardiac causes had hypertension, 83% smoked, and 5% had a history of cerebrovascular acci dent. Thirty-six of the 112 (32%) patients had had a vascular reconstructive procedure previously. The mortality rate of 26% (29/112) reported in this series of patients undergoing revision of BK to AK amputation is similar to that in the reported literature for isolated primary AK amputation. The level of amputa tion was based on vascular evaluation and clinical judgment at the time of oper ation. The lack of increased morbidity and mortality should encourage surgeons to persist in doing as many BK amputations as clinically warranted to improve rehabilitation; no increased mortality occurs in the requirement for a second operative procedure.

Carotid surgery without preoperative arteriography was performed in 101 consecutive patients with an average age of 68.5 years and almost equal sex distribution. This prospective study analyzed risk factors, operative approach, bruits, indications for surgery, and outcome. All patients were studied by real-time B-mode ultrasound and spectral analysis and none were referred for arteriogram. The majority of patients had a standard carotid endarterectomy, and the findings at surgery correlated with noninvasive imaging. No mortality was recorded in this series of patients; a 1% rate of neurologic morbidity was noted. These results suggest that one can safely operate on the basis of a duplex scan. A preoperative arteriogram is not always necessary for carotid evaluation.

Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 microg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area x 100; p0.05) but had no effect at lower (5 microg/kg/day) or higher (20 microg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function.

The pathophysiology of restenosis following balloon catheterization involves a sequence of events similar to wound healing (1). Mechanical stress and mitogens released by cells at the site of injury activate quiescent vascular smooth muscle cells (VSMC) of the contractile phenotype to dedifferentiate to the synthetic phenotype and, subsequently, divide. Activated VSMC of the synthetic phenotype migrate through breaks in the internal elastic lamina to the intima where they continue to proliferate and synthesize abundant extracellular matrix (ECM), resulting in an increased neointimal mass. This intimal hyperplasia has been suggested to contribute to a decrease in lumen diameter and patency of the vessel resulting in ischemic symptoms. It should be noted, however, that the contribution of intimal thickening to the pathophysiology of restenosis has recently been questioned.

Traumatic occlusion of lower extremity polytetrafluoroethylene arterial grafts is exceedingly rare. We report a patient who suffered a supracondylar femur fracture resulting in shortening of her right lower extremity with kinking and thrombosis of her above-knee polytetrafluoroethylene arterial graft. This is the first report in the English language of prosthetic graft occlusion as a result of traumatic limb shortening. The graft thrombus was successfully lysed by use of intraarterial urokinase, and the kink was repaired by graft resection and reanastomosis. The mechanism of injury and treatment are discussed.

Vasodilator responses to human adrenomedullin (hADM), a newly discovered hypotensive peptide, human calcitonin gene-related peptide-α (hCGRP-α) and hCGRP-β, which share structural homology with hADM, were compared in the hindlimb vascular bed of the cat under constant flow conditions. Injections of hADM (0.003–1 nmol), hCGRP-α, and hCGRP-β (0.003–0.3 nmol) into the perfusion circuit caused dose-related decreases in hindlimb perfusion pressure. Vasodilator responses to hCGRP-α and hCGRP-β were similar in potency and duration, and the doses of hCGRP-α and hCGRP-β required to reduce hindlimb perfusion pressure 40 mm Hg (ED40 mm Hg) were significantly lower than the ED40 mm Hg for hADM. The duration of the hindlimb vasodilator responses to hCGRP-α and hCGRP-β were significantly longer than the duration of the response to hADM. Amylin, a peptide that shares structural homology with ADM and with CGRP, had no significant effect on hindlimb perfusion pressure when injected in doses up to 1 nmol. Decreases in hindlimb perfusion pressure in response to hADM, hCGRP-α, and hCGRP-β were not altered by L-N5-(1-iminoethyl)-ornithine (L-NIO) in a dose of the nitric oxide synthase inhibitor that decreased the vasodilator response to acetylcholine or by the cyclooxygenase inhibitor, meclofenamate, in a dose that decreased the vasodilator response to archidonic acid. The present data demonstrate that hADM, hCGRP-α, and hCGRP-β have potent, but relatively short-lasting, vasodilator activity, and that vasodilator responses are not dependent on the release of nitric oxide or vasodilator prostaglandins in the hindlimb vascular bed of the cat. (Mol Cell Biochem 176: 5–11, 1997)

The effects of an anti-P-selectin monoclonal antibody (MAb, PB 1.3; Cytel Corporation) on neoendothelialization; neoendothelial function, as evidenced by acetylcholine-induced relaxation (nitric oxide formation); and intimal hyperplasia following embolectomy catheter-induced injury to the rabbit thoracic aorta were investigated. Catheter injury was induced in two groups of New Zealand White rabbits. One group received no treatment, while the second group received short-term treatment with the MAb (i.p., immediately before and 12 h after induction of catheter injury). A third group underwent a sham operation and served as uninjured controls. Following sacrifice at 2 weeks after injury, aortic rings were assessed for degree of intimai hyperplasia, neoendothelial morphology (scanning electron microscopy), and acetylcholine-induced relaxation. Aortic tissue from catheter-injured animals that received treatment exhibited improved neoendothelial morphology, as compared with tissue from untreated but catheterized animals; however, no statistically significant attenuation of the hyperplastic response or improvement in the attenuated neoendothelial-dependent acetylcholine-induced relaxant response that is characteristic of neoendothelium that forms after catheter denudation was observed. These data suggest that short-term attenuation of P-selectin-mediated polymorphonuclear leukocyte (PMN)/endothelium, PMN/platelet interactions, and/or thrombin formation beneficially affects neoendothelialization of the vascular wall following balloon catheter-induced injury. (Mol Cell Biochem 176: 13–20, 1997)

Iliac vein compression syndrome is a clinical condition that occurs as a result of compression of the left iliac vein between the right iliac artery and the fifth lumbar vertebrae. Patients usually have marked edema of the left leg. We report a case of a 16-year-old man who sought medical attention with significant left lower leg edema and four previous episodes of left leg cellulitis. Evaluation demonstrated venous hypertension as a result of left iliac vein compression. The patient underwent surgical correction; his symptoms resolved. Details and management of the case are presented and discussed. A review of the current literature regarding this condition also is included. (J Vasc Surg 1996;24:477-81.)

Regrowth of a neoendothelial vascular lining and intimal hyperplasia (IH) occur subsequent to balloon catheter injury to the vascular wall (Eldor et al., 1981; Barone et al., 1989; Weidinger et al., 1990; Saroyan et al., 1992). Prostacyclin (prostaglandin I2, PGI2) and nitric oxide (NO) are formed by the endothelium and have been reported to inhibit vascular smooth muscle proliferation (Garg and Hassid, 1989). However, the in vivo relationship between IH and PGI2 or endothelium-derived relaxing factor (EDRF) [which is thought to be NO] formation by the neoendothelium has yet to be firmly established. Earlier studies have demonstrated that balloon catheter-induced injury to the vascular wall is associated with a decrease (Eldor et al., 1981), an increase (Mehta et al., 1982), or no change in PGI2 formation (Hoover et al., 1989). Additionally, balloon catheter-induced injury has been reported to produce an initial decrease in EDRF generation with a return to control by 4 weeks, although the recovery of endothelium-dependent relaxation appears to depend on the severity of the initial injury (Weidinger et al., 1990). Others have shown a persistent defect in the response to various endothelium-dependent vasodilators (Shimokawa et al., 1987). Thus, although there is evidence that balloon injury and subsequent IH can alter both PGI2 and EDRF generation, there is little information on the effect of balloon catheter-induced vascular injury on the generation of PGI2 and EDRF in animals that received the same degree of injury. Therefore, the present study was undertaken to investigate the time course of recovery of vascular generation of PGI2 and EDRF following catheter-induced injury. We also tested the hypothesis that administration of LARG, the precursor of NO, inhibits balloon catheter-induced IH.

Visceral artery aneurysms are unusual lesions. However the frequency of diagnosis has increased in recent years as a result of increased utilization of arteriogram and computed tomographic (CT) scan. When diagnosed in conjunction with other syndromes, alternative treatment options can be utilized. The present case discusses a 67-year-old black male who presented with a right renal mass and a celiac artery aneurysm. The renal mass was diagnosed as an oncocytoma. This unique anatomy enabled us to perform a right nephrectomy in conjunction with a celiac artery aneurysmectomy with primary anastomosis between the right renal artery and common hepatic artery. This case demonstrates our approach to an unusual problem.

The lithotomy position is commonly used during the performance of a variety of abdominal and pelvic operations. Previous publications reporting complications with these operations have been largely anecdotal. We report our experience with eight patients over the past four years who have suffered serious lower extremity complications following operations in which the lithotomy position was used. The average time in the lithotomy position for our patients was 7.4 hours (range: 3.7–12 hours). The mean interval between the original operation and the secondary operation to treat the lower extremity complication was 18.9 hours (range: 2–51 hours). The average hospital length of stay for these patients, 38.4 days (range: 11–119 days), was often prolonged as a direct result of their limb complication. Serious lower extremity complications may result from operations in which the lithotomy position is used. To prevent such complications, strict attention should be paid to the positioning of the limbs in the operating room and the time in the lithotomy position should be minimized. Perioperative monitoring of the lower extremity circulation and compartment pressures are essential in these patients since early detection and treatment of these complications is the only way to prevent permanent limb injury.

Transtracheal needle catheter ventilation (TNCV) may be used as an alternative airway when contraindications to endotracheal intubation exist. A feline model tested the efficacy of low-flow oxygen delivery, and initial data were gathered to define proper catheter calibers to effect adequate oxygenation and ventilation. Cats were anesthetized, trachea intubated, and ventilated for 30 minutes with a pressure-regulated ventilator. Arterial and venous pressures were monitored, and a chest tube was inserted to measure intrathoracic pressures. Arterial blood gas analysis was performed every five minutes during the baseline period. The endotracheal tube was then removed, the trachea cross-clamped, and TNCV instituted. Oxygen flow rates of 1, 3, and 5 L/min were varied with catheter sizes of 14, 16, and 18 g. Data demonstrated that TNCV provided adequate oxygenation and ventilation with flow rates of 3 and 5 L/min with the 14- and 16-g catheters. Satisfactory oxygenation could be obtained with these flow rates with the 18-g catheter, but ventilation was inadequate. Ventilation was unsatisfactory with the 1 L/min flow rate in all catheter sizes. These preliminary data indicate that a minimum catheter:trachea cross-sectional area ratio of 0.03 may be required to obtain oxygenation and ventilation with low-flow oxygen rates of 3 to 5 L/min in cats.

Prostacyclin (PGI2) and thromboxane A2 (TxA2) formation by whole-tissue segments of nine carotid endarterectomy specimens (CES), five normal aortic specimens (NAS), six saphenous vein specimens (SVS), and four platelet samples were determined by incubation with 10 mumol/L 1-14C-radiolabeled prostaglandin endoperoxide H2 (PGH2), and in other experiments with and without 10 mumol/L of CGS 13080, a TxA2 synthase inhibitor. PGI2 formation (expressed as picomoles 6-keto-PGF1 alpha/2-min incubation per sample) by nonatheromatous proximal intima of CES (307 +/- 23, mean +/- standard error) and distal intima of CES (260 +/- 22) was not statistically different; however, it was greater than atheromatous transitional plaque (159 +/- 13 pmol) (p less than 0.01) and ulceration regions (140 +/- 15 pmol) (p less than 0.01) of CES, NAS (204 +/- 16 pmol) (p less than 0.01), and SVS (165 +/- 9 pmol) (p less than 0.01). TxA2 formation (expressed as picomoles TxB2/2-min incubation per sample) by CES ulceration (51 +/- 2 pmol) was low but greater than proximal (17 +/- 2 pmol) (p less than 0.01), distal (19 +/- 3 pmol) (p less than 0.01), and transitional (23 +/- 3 pmol) (p less than 0.01) regions. TxA2 formation by NAS and SVS was not detected (less than 10 pmol). CGS 13080 inhibited TxA2 formation by CES below the limits of detection. Incubation of 1.9 x 10(5) intact platelets with 10 mumol/L of PGH2 formed a quantity of TxA2 equal to that of CES ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)

In evaluation of extracranial carotid vascular disease, the use of arteriography has long been considered essential. With increasing expertise in noninvasive testing, the importance of extensive dye studies is being questioned. The data presented herein indicate that proper preangiographic evaluation of the patient population drastically reduces the possibility of missing significant intrathoracic pathologic processes. Two subsets of patients should be recommended routinely for dye studies: those patients with unequal upper-extremity blood pressures and those without pathologic neck findings on noninvasive testing to account for their symptoms. When these patients are recognized as having the potential for intrathoracic disease, dye studies can be performed in situations that will generate the highest yield. Even with the continued use of dye studies in evaluation of cerebrovascular insufficiency, elimination of the aortic arch study will drastically reduce the dye load and, thus, the associated morbidity.

One thousand consecutive cerebral arteriograms for suspected carotid artery disease were retrospectively evaluated for the intracranial disease component. Only 784 patients (78 percent) had arteriograms of the intracranial circulation. Forty-six patients (6 percent) had siphon stenosis in the range of 5 to 70 percent. No patient had a lesion encompassing more than 75 percent of the vessel diameter. Thirteen patients (2 percent) had intracranial aneurysms. All patients were asymptomatic from the standpoint of their aneurysms and none required surgical intervention. One additional patient was noted to have an intracranial tumor, which was confirmed by computerized tomography. In this patient population, intracranial dye study did not provide information that altered management.

International audience; Membrane potential homeostasis is essential for cell survival. Defects in membrane potential lead to pleiotropic phenotypes, consistent with the central role of membrane energetics in cell physiology. Homologs of the progestin and AdipoQ receptors (PAQRs) are conserved in multiple phyla of Bacteria and Eukarya. In eukaryotes, PAQRs are proposed to modulate membrane fluidity and fatty acid (FA) metabolism. The role of bacterial homologs has not been elucidated. Here, we use Escherichia coli and Bacillus subtilis to show that bacterial PAQR homologs, which we name "TrhA," have a role in membrane energetics homeostasis. Using transcriptional fusions, we show that E. coli TrhA (encoded by yqfA) is part of the unsaturated fatty acid biosynthesis regulon. Fatty acid analyses and physiological assays show that a lack of TrhA in both E. coli and B. subtilis (encoded by yplQ) provokes subtle but consistent changes in membrane fatty acid profiles that do not translate to control of membrane fluidity. Instead, membrane proteomics in E. coli suggested a disrupted energy metabolism and dysregulated membrane energetics in the mutant, though it grew similarly to its parent. These changes translated into a disturbed membrane potential in the mutant relative to its parent under various growth conditions. Similar dysregulation of membrane energetics was observed in a different E. coli strain and in the distantly related B. subtilis. Together, our findings are consistent with a role for TrhA in membrane energetics homeostasis, through a mechanism that remains to be elucidated.

Photosystem I (PSI) were reported as trimeric complexes in most characterized cyanobacteria, yet monomers in plants and algae PSI. Recent reports on tetrameric PSI raised questions regarding its structural basis, physiological role, phylogenetic distribution and evolutionary significance. In this study, by examining PSI in 61 cyanobacteria, we show that tetrameric PSI, correlating with a uniquepsaLgene and genomic structure, is widespread in the heterocyst-forming cyanobacteria and their close relatives. Physiological studies on these cyanobacteria revealed that tetrameric PSI is favored under high light, with an increased content of novel PSI-bound carotenoids (myxoxanthophyll, canthaxanthan and echinenone). Together this work suggests that tetrameric PSI is an adaptation to high light, along with results showing that change in PsaL leads to trimeric PSI monomerization, supporting the hypothesis of tetrameric PSI being the evolutionary intermediate in the transition from cyanobacterial trimeric PSI to monomeric PSI in plants and algae.