Timing of Venous Thromboembolism Prophylaxis Initiation and Complications in Polytrauma Patients with High-Risk Bleeding Orthopedic Interventions: A Nationwide Analysis.

INTRODUCTION: There are no clear recommendations for the perioperative timing and initiation of venous thromboembolism pharmacologic prophylaxis (VTEp) among polytrauma patients undergoing high-risk bleeding orthopedic operative intervention, leading to variations in VTEp administration. Our study examined the association between the timing of VTEp and VTE complications in polytrauma patients undergoing high-risk operative orthopedic interventions nationwide. METHODS: A retrospective cohort study of trauma patients ≥18 years who underwent high-risk bleeding operative orthopedic interventions for pelvic, hip, and femur fractures within 24 hours of admission at American College of Surgeons (ACS) verified trauma centers using the 2019-2020 ACS-TQIP databank. We excluded patients with a competing risk of non-orthopedic surgical bleeding. We assessed operative orthopedic polytrauma patients who received VTEp within 12 hours of orthopedic surgical intervention compared to VTEp received beyond 12 hours of intervention. The primary outcome assessed was overall VTE events. Secondary outcomes were orthopedic reinterventions within 72 hours after primary orthopedic surgery, DVT, and PE rates. RESULTS: The study included 2,229 patients who underwent high-risk orthopedic operative intervention. The median time to VTEp initiation was 30 hours (IQR 18, 44). After adjustment for baseline patient, injury, and hospital characteristics, VTEp initiated more than 12 hours from primary orthopedic surgery was associated with increased odds of VTE (aOR 2.02; 95% CI 1.08-3.77). Earlier initiation of prophylaxis was not associated with an increased risk for surgical reintervention (HR 0.90; 95% CI 0.62-1.34). CONCLUSIONS: Administering VTEp within 24 hours of admission and within 12 hours of major orthopedic surgery involving the femur, pelvis, or hip demonstrated an associated decreased risk of in-hospital VTE without an accompanying elevated risk of bleeding-related orthopedic re-intervention. Clinicians should reconsider delays in initiating or withholding perioperative VTEp for stable polytrauma patients needing major orthopedic intervention. LEVEL OF EVIDENCE: Level III, Therapeutic.

Long-term outcomes of autologous vein bypass for repair of upper and lower extremity major arterial trauma.

OBJECTIVE: Autologous vein is the preferred bypass conduit for extremity arterial injuries owing to superior patency and low infection risk; however, long-term data on outcomes in civilians are limited. Our goal was to assess short- and long-term outcomes of autologous vein bypass for upper and lower extremity arterial trauma. METHODS: A retrospective review was performed of patients with major extremity arterial injuries (2001-2019) at a level I trauma center. Demographics, injury and intervention details, and outcomes were recorded. Primary outcomes were primary patency at 1 year and 3 years. Secondary outcomes were limb function at 6 months, major amputation, and mortality. Multivariable analysis determined risk factors for functional impairment. RESULTS: There were 107 extremity arterial injuries (31.8% upper and 68.2% lower) treated with autologous vein bypass. Mechanism was penetrating in 77% of cases, of which 79.3% were due to firearms. The most frequently injured vessels were the common and superficial femoral (38%), popliteal (30%), and brachial arteries (29%). For upper extremity trauma, concomitant nerve and orthopedic injuries were found in 15 (44.1%) and 11 (32.4%) cases, respectively. For lower extremities, concomitant nerve injuries were found in 10 (13.7%) cases, and orthopedic injuries in 31 (42.5%). Great saphenous vein was the conduit in 96% of cases. Immediate intraoperative bypass revision occurred in 9.3% of patients, most commonly for graft thrombosis. The in-hospital return to operating room rate was 15.9%, with graft thrombosis (47.1%) and wound infections (23.5%) being the most common reasons. The median follow-up was 3.6 years. Kaplan-Meier analysis showed 92% primary patency at 1 year and 90% at 3 years. At 6 months, 36.1% of patients had functional impairment. Of patients with functional impairment at 6 months, 62.9% had concomitant nerve and 60% concomitant orthopedic injuries. Of those with nerve injury, 91.7% had functional impairment, compared with 17.8% without nerve injury (P < .001). Of patients with orthopedic injuries, 51.2% had functional impairment, vs 25% of those without orthopedic injuries (P = .01). On multivariable analysis, concomitant nerve injury (odds ratio, 127.4; 95% confidence interval, 17-957; P <. 001) and immediate intraoperative revision (odds ratio, 11.03; 95% confidence interval, 1.27-95.55; P = .029) were associated with functional impairment. CONCLUSIONS: Autologous vein bypass for major extremity arterial trauma is durable; however, many patients have long-term limb dysfunction associated with concomitant nerve injury and immediate intraoperative bypass revision. These factors may allow clinicians to identify patients at higher risk for functional impairment, to outline patient expectations and direct rehabilitation efforts toward improving functional outcomes.

Intern Experience Reflects Information Gathered During the Virtual Interview Process.

OBJECTIVE: The onset of the coronavirus 2019 (COVID-19) pandemic brought many changes to the residency application process including transitioning to a virtual interview platform, which continues today. The transition brought many concerns from general surgery applicants about their ability to obtain adequate information about a program virtually. We sought to characterize how information presented by programs during the first ever virtual interview cycle matched the experience of general surgery interns after training at a program for 1 year. DESIGN, SETTING, AND PARTICIPANTS: In May of 2022, a survey was distributed to 243 program directors who were asked to forward it to their general surgery categorical interns who matched during the 2021 virtual match cycle. Demographics, resources used to determine an impression of a program, and correlations between information presented virtually and what was subsequently experienced as an intern were collected. RESULTS: Forty-six program directors confirmed forwarding the survey to their categorical interns. A total of 102 general surgery interns completed the survey. Most interns (88.2%) agreed that their experience matched expectations based on information received through the virtual interview process and 98% of interns were satisfied with their experience at their training program. Interviews with faculty (40.0%), residents (68.0%) and the program web site (29.0%) were the top 3 resources used to create the most accurate impression of a program. Interns felt they were well informed during the virtual interview experience about support from fellow residents (84.3%), culture (73.0%), surgical volume (72.5%), and intern operative experience (71.6%). In addition, 65.7% of participants thought they were able to obtain a good understanding of the program's culture from the virtual process. However, 16.7% thought that their program unintentionally misrepresented aspects of the training program. CONCLUSIONS: The faculty and residency interviews were the most important factors in program ranking and most participants agreed that their virtual interview experience matched their expectations during their intern year. Most interns felt they were able to obtain a good understanding of the program's culture from the virtual process. In addition, a majority of interns felt well informed during the interview on aspects ranging from surgical volume, autonomy, and work hours to support from faculty and residents. If virtual interviews are to continue, residents can be satisfied that information gathered virtually will match the reality of their training. Programs should continue to make every effort to present their program realistically.

Antibiotic use in acute mesenteric ischemia: a review of the evidence and call to action.

Acute mesenteric ischemia (AMI) is a life-threatening condition with a high mortality rate. The standard practice after making the diagnosis includes aggressive resuscitation, anticoagulation, followed by revascularization and resection of necrotic bowel. The role of empiric antibiotics in the management of AMI is not well defined in the literature. This review article aims to examine our current understanding on this matter, based on bench research and clinical studies. It is demonstrated in animal study model that the ischemia/reperfusion (I/R) injury damages intestinal epithelium, and subsequently lead to barrier dysfunction, a condition that can support bacterial translocation through a complex interplay between the intestinal epithelium, the intestinal immune system and the intestine's endogenous bacterial population. Based on this mechanism, it is possible that the use of antibiotics may help mitigate the consequences of I/R injury, which is examined in few animal studies. In clinical practice, many guidelines support the use of prophylactic antibiotics, based on a meta-analysis of randomized control trials (RCTs) demonstrating the benefit of antibiotics in multi-organ dysfunction syndrome. However, there is no direct reference to AMI in this meta-analysis. Most clinical studies that focus on AMI and mentions the use of antibiotics are retrospective and single institution, and very few comments on the role of antibiotics in their discussions. We conclude that there is limited evidence in literature to support the use of prophylactic antibiotic in AMI to improve outcome. More clinical studies with high level of evidence and basic science research are needed to improve our understanding on this topic and ultimately help build a better clinical pathway for patients with AMI.

Outcomes following ipsilateral great saphenous vein bypass for lower extremity arterial injuries.

OBJECTIVE: Use of autologous great saphenous vein (GSV) grafts for repair of extremity arterial injuries is well established. Contralateral great saphenous vein (cGSV) is traditionally used in the setting of lower extremity vascular injury given the risk of occult ipsilateral superficial and deep venous injury. We evaluated outcomes of ipsilateral GSV (iGSV) bypass in patients with lower extremity vascular trauma. METHODS: Patient records at an ACS verified Level I urban trauma center between 2001 and 2019 were retrospectively reviewed. Patients who sustained lower extremity arterial injuries managed with autologous GSV bypass were included. Propensity-matched analysis compared the iGSV and cGSV groups. Primary graft patency was assessed via Kaplan-Meier analysis at 1-year and 3-years following the index operation. RESULTS: A total of 76 patients underwent autologous GSV bypass for lower extremity vascular injuries. 61 cases (80%) were secondary to penetrating trauma, and 15 patients (20%) underwent repair with iGSV bypass. Arteries injured in the iGSV group included popliteal (33.3%), common femoral (6.7%), superficial femoral (33.3%), and tibial (26.7%), while those in the cGSV group included common femoral (3.3%), superficial femoral (54.1%), and popliteal (42.6%). Reasons for using iGSV included trauma to the contralateral leg (26.7%), relative accessibility (33.3%), and other/unknown (40%). On unadjusted analysis, iGSV patients had a higher rate of 1-year amputation than cGSV patients (20% vs. 4.9%), but this was not statistically significant (P = 0.09). Propensity matched analysis also found no significant difference in 1-year major amputation (8.3% vs. 4.8%, P = 0.99). Regarding ambulatory status, iGSV patients had similar rates of independent ambulation (33.3% vs. 38.1%), need for assistive devices (58.3% vs. 57.1%), and use of a wheelchair (8.3% vs. 4.8%) compared cGSV patients at subsequent follow-up (P = 0.90). Kaplan-Meier analysis of bypass grafts revealed comparable primary patency rates for iGSV versus cGSV bypasses at 1-year (84% vs. 91%) and 3-years post-intervention (83% vs. 90%, P = 0.364). CONCLUSION: Ipsilateral GSV may be used as a durable conduit for bypass in cases of lower extremity arterial trauma where use of contralateral GSV is not feasible, with comparable long-term primary graft patency rates and ambulatory status.

Surgical stabilization versus nonoperative treatment for flail and non-flail rib fracture patterns in patients with traumatic brain injury.

PURPOSE: Literature on outcomes after SSRF, stratified for rib fracture pattern is scarce in patients with moderate to severe traumatic brain injury (TBI; Glasgow Coma Scale ≤ 12). We hypothesized that SSRF is associated with improved outcomes as compared to nonoperative management without hampering neurological recovery in these patients. METHODS: A post hoc subgroup analysis of the multicenter, retrospective CWIS-TBI study was performed in patients with TBI and stratified by having sustained a non-flail fracture pattern or flail chest between January 1, 2012 and July 31, 2019. The primary outcome was mechanical ventilation-free days and secondary outcomes were in-hospital outcomes. In multivariable analysis, outcomes were assessed, stratified for rib fracture pattern. RESULTS: In total, 449 patients were analyzed. In patients with a non-flail fracture pattern, 25 of 228 (11.0%) underwent SSRF and in patients with a flail chest, 86 of 221 (38.9%). In multivariable analysis, ventilator-free days were similar in both treatment groups. For patients with a non-flail fracture pattern, the odds of pneumonia were significantly lower after SSRF (odds ratio 0.29; 95% CI 0.11-0.77; p = 0.013). In patients with a flail chest, the ICU LOS was significantly shorter in the SSRF group (beta, - 2.96 days; 95% CI - 5.70 to - 0.23; p = 0.034). CONCLUSION: In patients with TBI and a non-flail fracture pattern, SSRF was associated with a reduced pneumonia risk. In patients with TBI and a flail chest, a shorter ICU LOS was observed in the SSRF group. In both groups, SSRF was safe and did not hamper neurological recovery.

Emesis of an enteral bullet: A rare case of bullet embolism to the thoracic esophagus.

A case of migration of a foreign body from the stomach to the thoracic esophagus is described. The bullet was successfully retrieved endoscopically after exploratory laparotomy was performed to address the patient's injuries. Enteral migration of bullets is a rare phenomenon that should be considered when the location of retained ballistic fragments is inconsistent with gunshot wounds and expected trajectories.

High Mortality and Venous Thromboembolism Risk Following Major Penetrating Abdominal Venous Injuries.

BACKGROUND: Penetrating injuries to the inferior vena cava and/or iliac veins are a source of hemorrhage but may also predispose patients to venous thromboembolism (VTE). We sought to determine the relationship between iliocaval injury, VTE and mortality. METHODS: The National Trauma Data Bank was queried for penetrating abdominal trauma from 2015-2017. Univariate analyses compared baseline characteristics and outcomes based on presence of iliocaval injury. Multivariable analyses determined the effect of iliocaval injury on VTE and mortality. RESULTS: Of 9,974 patients with penetrating abdominal trauma, 329 had iliocaval injury (3.3%). Iliocaval injury patients were more likely to have a firearm mechanism (83% vs. 43%, P < 0.001), concurrent head (P = 0.036), spinal cord (P < 0.001), and pelvic injuries (P < 0.001), and higher total injury severity score (median 20 vs. 8.0, P < 0.001). They were more likely to undergo 24-hr hemorrhage control surgery (69% vs. 17%, P < 0.001), but less likely to receive VTE chemoprophylaxis during admission (64% vs. 68%, P = 0.04). Of patients undergoing iliocaval surgery, 64% underwent repair, 26% ligation, and 10% unknown. Iliocaval injury patients had higher rates of VTE (12% vs. 2%), 24-hr mortality (23% vs. 2.0%) and in-hospital mortality (33% vs. 3.4%) (P < 0.001 for all). VTE rates were similar following repair (14%) and ligation (17%). Iliocaval injury patients also had higher rates of cardiac complications (10.3% vs. 1.4%), acute kidney injury (8.2% vs. 1.3%), extremity compartment syndrome (4.0 vs. 0.2%), and unplanned return to OR (7.9% vs. 2.5%) (P < 0.001 for all). In multivariable analyses, iliocaval injury was independently associated with risk of VTE (OR 2.12; 95% CI, 1.29-3.48; P = 0.003), and in-hospital mortality (OR = 9.61; 95% CI, 4.96-18.64; P < 0.001). CONCLUSION: Iliocaval injuries occur in <5% of penetrating abdominal trauma but are associated with more severe injury patterns and high mortality rates. Regardless of repair type, survivors should be considered high risk for developing VTE.

The majority of major amputations after resuscitative endovascular balloon occlusion of the aorta are associated with preadmission trauma.

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially life-saving intervention. However, recent reports of associations with limb loss and mortality have called its safety into question. We aimed to evaluate patient and hospital characteristics associated with major amputation and in-hospital mortality among patients undergoing REBOA for trauma. METHODS: The National Trauma Data Bank (2015-2017) was queried for patients presenting to trauma centers and treated with REBOA. We included REBOA performed on hospital day 1 in patients who survived 6 or more hours from presentation. Univariable and multivariable analyses evaluated associations with major amputation and in-hospital mortality. RESULTS: A total of 316 patients underwent REBOA and survived in the acute period after presentation. Overall, mean age was 45 ± 20 years and the majority were male (73%) and White (56%). Most patients presented to level I trauma centers (72%) after blunt injuries (79%) with an average Injury Severity Score (ISS) of 31 ± 15, indicating major trauma. In 15 patients (5%), there were 18 major amputations-7 above knee and 11 below knee. A subgroup of 11 amputations were either traumatic amputations (73%) or mangled limbs requiring amputation within 24 hours (27%). Of the remaining amputations, 71% were associated with ipsilateral vascular or orthopedic lower extremity injuries of serious to severe Abbreviated Injury Scale severity. Comparing patients with amputations with those without amputations, there were no significant differences in patient demographics, comorbidities, or hospital characteristics. During hospitalization, patients requiring amputation more frequently received open peripheral vascular interventions (40% vs 10%; P = .002), underwent similar numbers of endovascular interventions (6.7% vs 4.7%; P = .5), and more often developed compartment syndrome (13% vs 2%; P = .04). Overall, there were 110 deaths (35%). The major amputation prevalence was similar between patients who died vs those who survived (3.6% vs 5.3%; P = .5). In multivariable analysis, prehospital cardiac arrest (odds ratio [OR], 8.47; 95% confidence interval [CI], 1.47-48.66; P = .02), penetrating vs blunt trauma (OR, 5.5; 95% CI, 1.05-28.82; P = .04), decreased Glasgow Coma Scale score (OR, 1.18; 95% CI, 1.05-1.32; P = .01), older age (OR, 1.06; 95% CI, 1.03-1.10; P < .001), and increased Injury Severity Score (OR, 1.05; 95% CI, 1.0-1.1; P = .03) were associated with higher mortality. CONCLUSIONS: The majority of major amputations in patients undergoing REBOA were secondary to the initial traumatic mechanism. Injury type and severity, as well as initial hemodynamic derangements, are associated with mortality after REBOA. Despite concerns about prohibitive limb complications of REBOA, baseline injuries seem to be the primary cause of limb loss, but further prospective analysis is needed.

Outcome after surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures and moderate to severe traumatic brain injury (CWIS-TBI).

BACKGROUND: Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared with nonoperative management, is associated with favorable outcomes in patients with TBI. METHODS: A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were intensive care unit length of stay and hospital length of stay, tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS score, 9-12) and severe (GCS score, ≤8) TBI. RESULTS: The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. The SSRF was performed at a median of 3 days, and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.38-0.98; p = 0.043) and 30-day mortality (OR, 0.32; 95% CI, 0.11-0.91; p = 0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (OR, 0.19; 95% CI, 0.04-0.88; p = 0.034). CONCLUSION: In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI. LEVEL OF EVIDENCE: Therapeutic, level IV.

The Boston Medical Center Coronavirus Disease 2019 (COVID-19) Procedure Team: Optimizing the surgeon's role in pandemic care at a safety-net hospital.

BACKGROUND: The coronavirus disease 2019 pandemic has claimed many lives and strained the US health care system. At Boston Medical Center, a regional safety-net hospital, the Department of Surgery created a dedicated coronavirus disease 2019 Procedure Team to ease the burden on other providers coping with the surge of infected patients. As restrictions on social distancing are lifted, health systems are bracing for additional surges in coronavirus disease 2019 cases. Our objective is to quantify the volume and types of procedures performed, review outcomes, and highlight lessons for other institutions that may need to establish similar teams. METHODS: Procedures were tracked prospectively along with patient demographics, immediate complications, and time from donning to doffing of the personal protective equipment. Retrospective chart review was conducted to obtain patient outcomes and delayed adverse events. We hypothesized that a dedicated surgeon-led team would perform invasive bedside procedures expeditiously and with few complications. RESULTS: From March 30, 2020 to April 30, 2020, there were 1,196 coronavirus disease 2019 admissions. The Procedure Team performed 272 procedures on 125 patients, including placement of 135 arterial catheters, 107 central venous catheters, 25 hemodialysis catheters, and 4 thoracostomy tubes. Specific to central venous access, the average procedural time was 47 minutes, and the rate of immediate complications was 1.5%, including 1 arterial cannulation and 1 pneumothorax. CONCLUSION: Procedural complication rate was less than rates reported in the literature. The team saved approximately 192 hours of work that could be redirected to other patient care needs. In times of crisis, redeployment of surgeons (who arguably have the most procedural experience) into procedural teams is a practical approach to optimize outcomes and preserve resources.

Progressive Increase in Scholarly Productivity of New American Board of Anesthesiology Diplomates From 2006 to 2016: A Bibliometric Analysis.

BACKGROUND: Improving research productivity is a common goal in academic anesthesiology. Initiatives to enhance scholarly productivity in anesthesiology were proposed more than a decade ago as a result of emphasis on clinical work. We hypothesized that American Board of Anesthesiology diplomates certified from 2006 to 2016 would be progressively more likely to have published at least once during this time period. METHODS: A complete list of 17,332 new diplomates was obtained from the American Board of Anesthesiology for the years 2006 to 2016. These names were queried using PubMed, and the number of publications up to and including the diplomate's year of primary certification was recorded. Descriptive statistics and logistic regression analysis were used to analyze the association of the year of primary certification and whether a diplomate had published at least once. RESULTS: The percentage of American Board of Anesthesiology diplomates with ≥1 publication at the time of primary certification increased from 14.9% to 29.3% from 2006 to 2016. The mean number of publications per diplomate more than doubled from 0.31 to 0.79. Logistic regression analysis revealed the year of primary certification as significantly associated with having ≥1 publication (P < .001). Using 2006 as the reference year, odds of having published at least once were higher in the years 2010 to 2016, with the highest odds ratio of having a article published occurring in 2016: 2.359 (confidence interval, 1.978-2.812; P < .001). CONCLUSIONS: Publications by new diplomates of the American Board of Anesthesiology have increased between 2006 and 2016. Whether the observed increase in publications could reflect efforts to stimulate interest in academic objectives during training remains to be proven.

Implementation of a Novel Structured Social and Wellness Committee in a Surgical Residency Program: A Case Study.

This article provides a theoretical and practical rational for the implementation of an innovative and comprehensive social wellness program in a surgical residency program at a large safety net hospital on the East Coast of the United States. Using basic needs theory, we describe why it is particularly important for surgical residency programs to consider the residents sense of competence, autonomy, and belonging during residence. We describe how we have developed a comprehensive program to address our residents' (and residents' families) psychological needs for competence, autonomy, and belongingness.

Tactical medicine -- the Israeli revised protocol.

Limited conflicts and the war against terrorism, in particular, have changed the emphasis in the present trend from preparing to cope with full-scale wars to the need to combat in limited conflicts. This shift has affected significantly medical units' preparations. Law enforcement organizations have come together with medical first responders in a combined new model. This model is supposed to be adopted and utilized in combat and evolved from the civilian model toward a modus operandi that combines the tactical and medical protocols into a single algorithm, the "Tactical Combat Casualty Care" (TCCC). This TCCC model is believed to enhance the mutual understanding and cooperation of tactical and medical forces in combat and especially amongst special military units. Utilizing the model will be achieved by the development of well-matched standard operating procedures and sharing drills. All these acts are hoped to improve safety of the participating units and hopefully also the medical outcomes.

Differences in the sources of information and acquaintance with instructions between Dimona and the general population after a suicide bomber event.

A telephone survey among two randomly selected, representative samples of adults was conducted two days after a suicide bomber event in Dimona, Israel. Television, radio, Internet, and newspapers were more common sources of information in the general population, whereas friends, family, and the local authorities were the more common sources of information in Dimona. Higher acquaintance with police instructions and higher knowledge of the exact location of the event were found in the population of Dimona. Authorities must pay attention to this phenomenon and use the correct sources of information in each area in order to achieve better exposure of the target population to the police instructions after a terrorist event.

Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1.

The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that hypoxia-activated pulmonary artery AdvFBs exhibited pro-angiogenic properties and influenced the angiogenic phenotype of VVEC, in a process of cell-cell communication involving endothelin-1 (ET-1). We demonstrated that AdvFBs, either via co-culture or conditioned media, stimulated VVEC proliferation and augmented the self-assembly and integrity of cord-like networks that formed when VVECs where cultured on Matrigel. In addition, hypoxia-activated AdvFBs produced ET-1, suggesting a paracrine role for this pro-angiogenic molecule in these processes. When co-cultured on Matrigel, AdvFBs and VVECs self-assembled into heterotypic cord-like networks, a process augmented by hypoxia but attenuated by either selective endothelin receptor antagonists or oligonucleotides targeting prepro-ET-1 mRNA. From these observations, we propose that hypoxia-activated AdvFBs exhibit pro-angiogenic properties and, as such, communicate with VVECs, in a process involving ET-1, to regulate vasa vasorum neovascularization occurring in the adventitia of pulmonary arteries in response to chronic hypoxia.