Ambient pressure upregulates nitric oxide synthase in a phosphorylated-extracellular regulated kinase– and protein kinase C–dependent manner

PurposeUsing endothelial cell/smooth muscle cell (SMC) cocultures, we have demonstrated that pressurized endothelial cell coculture inhibits SMC proliferation and promotes apoptosis, and that this effect is transferable through pressurized endothelial medium. We now hypothesized that endothelial nitric oxide synthase (eNOS) plays a significant role in mediating these pressure-induced effects.MethodsConditioned media from endothelial cells and SMCs exposed to ambient and increased pressure were transferred to recipient SMCs. We counted cells after 5 days of incubation with these media and evaluated eNOS and inducible NOS (iNOS) levels by Western blot.ResultsConditioned media from pressurized endothelial cells significantly decreased recipient SMC counts. This effect was sustained when N-nitro-L-arginine-methyl ester (L-NAME) was added to recipient cells but abolished when L-NAME was added to donor cells. SMCs were then exposed to control and pressurized conditions in monoculture or in coculture with endothelial cells. Pressure and coculture caused similar increase in iNOS levels but had no additive effect in combination. Finally, endothelial cells were exposed to control and pressurized environments. Pressure caused a 24% ± 1.6% increase in eNOS protein (P = .04, n = 12). This effect was sustained when cells were treated with L-NAME (32% ± 1.6% increase, P = .02) but abolished when endothelial cells were treated with calphostin C or PD98059 to block protein kinase C (PKC) or extracellular regulated kinase (ERK). Pressure also increased endothelial phosphorylated ERK (p-ERK) by 1.8-fold to 2.6-fold compared with control conditions after exposure of 2, 4, and 6 hours (P = .02, n = 4). This increase was sustained after pretreatment with calphostin C.ConclusionPressure modulates endothelial cell effects on SMC growth by increasing eNOS in an ERK-dependent and PKC-dependent manner.Clinical RelevanceIntimal hyperplasia is the main cause for restenosis that complicates 10% to 30% of all such vascular procedures and 30% to 40% of endovascular procedures. This article provides some novel information about smooth muscle cell/endothelial cell interaction, one of the main regulators of vascular remodeling and intimal hyperplasia. The role of endothelial cell/smooth muscle cell interaction cannot be studied well in vivo because these interactions cannot be distinguished from other factors that coexist in vivo, such as flow dynamics, matrix proteins, inflammatory factors, and interactions with other cells in the vascular wall and in the bloodstream. In this work, we use pressure as a triggering stimulus to alter in vitro endothelial behavior and identify important changes in endothelial regulation of smooth muscle cell biology. The pathways involved in this process and discussed in this article could ultimately be used to manipulate endothelial cell/smooth muscle cell interaction in clinical disease

Outcome of elective endovascular abdominal aortic aneurysm repair in nonagenarians

ObjectiveCompared with open repair of abdominal aortic aneurysms (AAA), endovascular repair (EVAR) is associated with decreased perioperative morbidity and mortality in a standard patient population. This study sought to determine if the advantage of EVAR extends to patients aged ≥90 years.MethodsThis was a retrospective review from a prospectively maintained computerized database. Of the 322 patients aged ≥80 treated with EVAR from January 1997 to November 2007, 24 (1.9%) were aged ≥90. Mean age was 91.5 ± 1.5 years (range, 90-95 years), and 83.3% were men. Mean aneurysm size was 6.8 cm (range, 5.2-8.7 cm).ResultsMean procedural blood loss was 490 mL (range, 100-4150 mL), and 20.8% required an intraoperative transfusion. Mean postoperative length of stay was 6.0 days, (median, 4 days; mode, 1 day; range, 1-42 days), with 33.3% of patients discharged on the first postoperative day. Amongst the 24 patients, there were 6 (25.0%) perioperative major adverse events, and 2 patients died, for a perioperative mortality rate of 8.3%. Mean follow-up was 20.5 months (range, 1-49 months). Overall, three patients (12.5%) required a secondary intervention, comprising thrombectomy, angioplasty, and proximal cuff extension. No patients required conversion to open repair. Two patients (8.3%) died of AAA rupture at 507 and 1254 days. Freedom from all-cause mortality was 83.3% at 1 year and 19.3% at 5 years. Freedom from aneurysm-related mortality was 87.5% at 1 year and 73.2% at 5 years. Endoleak occurred in five patients (20.8%), with three type I and two of indeterminate type; of these, two patients with type I endoleak underwent secondary intervention at 153 and 489 days after EVAR, of which one case was successful.ConclusionOur study supports that EVAR in nonagenarians is associated with acceptable procedural success and perioperative morbidity and mortality. The medium-term results suggest that EVAR may be of limited benefit in very carefully selected patients who are aged ≥90 years

Time for radiation safety program guidelines for pregnant trainees and vascular surgeons

ObjectivesThe evolution of endovascular surgery has increased the vascular surgeon's exposure to radiation, raising concern for female vascular trainees and staff of childbearing years. We developed surveys for female trainees, established vascular surgeons, and program directors in vascular surgery to determine current practices with respect to pregnancy and radiation exposure guidelines.MethodsTwo surveys were conducted to evaluate radiation exposure during pregnancy. A survey of the members of the Association of Program Directors in Vascular Surgery was conducted in an attempt to gather information about existing program and institutional radiation policies and assess the need for standard guidelines. A second survey was given to women in vascular surgery in an effort to obtain opinions among concerned groups regarding establishment of a policy from women who were exposed to radiation during and after completion of vascular training.ResultsFifty-three of 181 female vascular surgeons (29% response rate) responded to the survey, with the majority (53% [28/53]) pregnant during training or practice. Though 68% of trainees and 82% of faculty performed endovascular procedures during pregnancy, only 42% of trainees and 50% of faculty wore a fetal badge. One trainee (3.7%) had complications during pregnancy that necessitated cessation of fluoroscopic procedures or limiting call. There were four practicing surgeons who had complications during their pregnancy. Of these, one was hospitalized with fetal decelerations secondary to excessive on-call obligations with double leading and heavy endovascular call coverage. The majority of women (>60%) felt supported by the program and that they were treated fairly. Over 90% of female trainees and faculty felt that establishment of guidelines for radiation safety for all vascular surgeons would be beneficial. Many (77%) felt that a policy would aid in the recruitment of talented women into the field. Thirty-two of 99 Association of Program Directors in Vascular Surgery program directors responded to the survey. Of the 32 program directors that responded (32% response rate), 75% would allow the pregnant trainee flexibility in rotation schedule. Finally, 75% of program directors support development of a national policy, and 81% would incorporate one into their program.ConclusionsThere is compelling interest to establish radiation safety guidelines for the pregnant trainee or vascular surgeon. Consideration should be given at the Society leadership level to develop and support radiation safety guidelines for all vascular surgeons