Prostaglandin receptor EP4 in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) pathogenesis is distinguished by vessel wall inflammation. Cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1, key components of the most well-characterized inflammatory prostaglandin pathway, contribute to AAA development in the 28-day angiotensin II infusion model in mice. In this study, we used this model to examine the role of the prostaglandin E receptor subtype 4 (EP4) and genetic knockdown of COX-2 expression (70% to 90%) in AAA pathogenesis. The administration of the prostaglandin receptor EP4 antagonist AE3-208 (10 mg/kg per day) to apolipoprotein E (apoE)-deficient mice led to active drug plasma concentrations and reduced AAA incidence and severity compared with control apoE-deficient mice (P < 0.01), whereas COX-2 genetic knockdown/apoE-deficient mice displayed only a minor, nonsignificant decrease in incidence of AAA. EP4 receptor protein was present in human and mouse AAA, as observed by using Western blot analysis. Aortas from AE3-208-treated mice displayed evidence of a reduced inflammatory phenotype compared with controls. Atherosclerotic lesion size at the aortic root was similar between all groups. In conclusion, the prostaglandin E(2)-EP4 signaling pathway plays a role in the AAA inflammatory process. Blocking the EP4 receptor pharmacologically reduces both the incidence and severity of AAA in the angiotensin II mouse model, potentially via attenuation of cytokine/chemokine synthesis and the reduction of matrix metalloproteinase activities.

Absence of right common iliac vein causing suprapubic and scrotal varices in a young athletic man.

We have described the case of a 26-year-old man who had presented to his primary care physician with persistent, painful varices across his lower abdomen and bilateral tender scrotal varicoceles, which intensified with exercise. Thorough investigations revealed a congenitally atretic right common iliac vein with right-to-left collateralization of the femoral and internal iliac veins. This shunting resulted in the development of suprapubic and pelvic and gonadal varicosities, which provided a critical venous outflow pathway for his right lower extremity. Heightened vigilance is, hence, paramount if our patient requires future abdominal and urologic procedures. Moreover, the present case has highlighted the importance of considering deep system venous anomalies when determining the differential diagnosis for venous diseases.

Low-Intensity Exercise Training Increases Heart Rate Variability in Patients With Peripheral Artery Disease.

Patients with peripheral artery disease (PAD), consistent with others with atherosclerotic occlusive disorders, have autonomic dysfunction (as measured by low heart rate variability [HRV]) that predisposes them to sympathetically mediated cardiac arrhythmias and sudden death. Exercise therapy has been shown to increase HRV in patients with coronary artery disease by increasing parasympathetic modulation of heart rate. This study quantified the circulatory and autonomic effects of a progressive, 12-week home-based, low-intensity (pain-free walking) exercise program in PAD and intermittent claudication. Participants (N = 33, mean age 67.8 8.1 years) were randomly assigned to either a walking group (n = 18), whose members performed a structured, 12-week, progressive walking program 5 days/week for 12 weeks, or a comparison group (n = 15), whose members performed usual activities. Circulatory measures (heart rate, blood pressure, and rate pressure product) and autonomic measures (HRV) were obtained at the beginning (Week 1) and end (Week 12) of the study. Minimal change in circulatory measures occurred. However, spectral analysis of HRV revealed that autonomic function improved significantly in members of the walking group; specifically, there was an increase in parasympathetic and a decrease in sympathetic modulation. Members of the walking group also significantly increased maximal walking distance. These findings suggest that a structured, low-intensity, high-frequency walking program improves autonomic function by increasing HRV in patients with PAD.

Management of Major Vascular Injuries: Neck, Extremities, and Other Things that Bleed.

Vascular injuries represent a significant burden of mortality and disability. Blunt injuries to the neck vessels can present with signs of stroke either immediately or in a delayed fashion. Most injuries are detected with computed tomography angiography and managed with either antiplatelet medications or anticoagulation. In contrast, patients with penetrating injuries to the neck vessels require airway management, hemorrhage control, and damage control resuscitation before surgical repair. The keys to diagnosis and management of peripheral vascular injury include early recognition of the injury; hemorrhage control with direct pressure, packing, or tourniquets; and urgent surgical consultation.

Remote Ischemic Preconditioning in High-risk Cardiovascular Surgery Patients: A Randomized-controlled Trial.

Remote ischemic preconditioning (RIPC) may reduce biomarkers of ischemic injury after cardiovascular surgery. However, it is unclear whether RIPC has a positive impact on clinical outcomes. We performed a blinded, randomized controlled trial to determine if RIPC resulted in fewer adverse clinical outcomes after cardiac or vascular surgery. The intervention consisted of 3 cycles of RIPC on the upper limb for 5 minutes alternated with 5 minutes of rest. A sham intervention was performed on the control group. Patients were recruited who were undergoing (1) high-risk cardiac or vascular surgery or (2) cardiac or vascular surgery and were at high risk of ischemic complications. The primary end point was a composite outcome of mortality, myocardial infarction, stroke, renal failure, respiratory failure, and low cardiac output syndrome, and the secondary end points included the individual outcome parameters that made up this score, as well as troponin-I values. A total of 436 patients were randomized and analysis was performed on 215 patients in the control group and on 213 patients in the RIPC group. There were no differences in the composite outcome between the 2 groups (RIPC: 67 [32%] and control: 72 [34%], relative risk [0.94 {0.72-1.24}]) or in any of the individual components that made up the composite outcome. Additionally, we did not observe any differences between the groups in troponin-I values, the length of intensive care unit stay, or the total hospital stay. RIPC did not have a beneficial effect on clinical outcomes in patients who had cardiovascular surgery.

The risk of rupture in untreated aneurysms: the impact of size, gender, and expansion rate.

OBJECTIVE: The purpose of this study was to establish the risk of rupture as related to size of abdominal aortic aneurysm (AAA), gender, and expansion of the aneurysm. METHODS: Between 1976 and 2001, 476 patients with conditions considered unfit for surgery with AAA 5.0 cm or more were followed with computed tomographic scans every 6 months until rupture, surgery, death, or deletion from follow-up. Surgery was performed for rupture (n = 22), improved medical condition (n = 37), increase in size (n = 95), symptoms (n = 17), and other reasons (n = 24). RESULTS: Fifty ruptures occurred during the follow-up period. The average risk of rupture (and standard error) in male patients with 5.0-cm to 5.9-cm AAA was 1.0% (0.01%) per year, in female patients with 5.0-cm to 5.9-cm AAA was 3.9% (0.15%) per year, in male patients with 6.0-cm or greater AAA was 14.1% (0.18%) per year, and in female patients with 6.0-cm or greater AAA was 22.3% (0.95%) per year. CONCLUSION: The risk of rupture in male patients with AAA 5.0 to 5.9 cm is low. The four-time higher risk of rupture in female patients with AAA 5.0 to 5.9 cm suggests a lower threshold for surgery be considered in fit women. The data regarding risk of rupture in patients with AAA 6.0 cm or more may allow more appropriate decision analysis for surgery in patients with unfit conditions with large AAA.

Selective management of abdominal aortic aneurysms smaller than 5.0 cm in a prospective sizing program with gender-specific analysis.

PURPOSE: We present extended follow-up findings of the Kingston prospective sizing program for patients with abdominal aortic aneurysm (AAA) smaller than 5.0 cm in diameter, with gender-specific analysis. METHODS: From 1976 to 2001, 895 patients (688 men, 207 women) with AAA smaller than 5.0 cm were entered, regardless of fitness, in a prospective sizing program in which computed tomography scans were obtained every 6 months. Operations were performed in fit patients with an increase in AAA size to 5 cm (n = 190), AAA expansion greater than 0.5 cm in 6 months (n = 27), or for other reasons (n = 33). Follow-up continued until AAA rupture, surgery, death, or removal from the program. RESULTS: No AAA smaller than 5.0 cm ruptured during prospective follow-up. There was a statistically significant increase in expansion rate relative to size at entry, with the highest mean expansion rate of 0.52 cm/y for AAA 4.5 to 4.9 cm in diameter. There was no significant difference in AAA expansion rate between men and women. The frequency of surgery was inversely related to age at entry, but was positively related to AAA size at entry, with patients with AAA 4.5 to 4.9 cm at entry 6.8 times more likely (95% confidence interval, 4.3-10.7) to undergo surgery than those with AAA 3.0 to 3.4 cm at entry. Women were older than men at entry, and age at entry in those undergoing surgery was significantly greater in women. CONCLUSIONS: The study confirms the results of the United Kingdom Small Aneurysm Trial and the Aneurysm Detection and Management Study, that is, that risk for rupture is extremely unlikely with AAA smaller than 5.0 cm, which enables safe follow-up surveillance programs in both men and women with AAA smaller than 5.0 cm.

Waiting time in relation to wait-list size at registration: statistical analysis of a waiting-list registry.

OBJECTIVE: To examine the relationship between the length of a waiting list for elective vascular surgery and the delay before undergoing the operation. METHODS: We undertook a prospective cohort study of patients registered on the waiting list for elective vascular surgery at an acute care hospital in Ontario. Regression analysis of wait times to express the admission rate in one group relative to another, with the ratio of rates being a measure of the difference between groups. RESULTS: List length at registration was associated with length of wait (log-rank test 596.4, p < 0.0001). Patients who were registered when the list length exceeded the weekly service capacity had 70% lower conditional probability of undergoing surgery than those on a list with fewer patients (rate ratio 0.30, 95% confidence interval [CI] 0.26-0.36) after adjustment for sex, age, procedure and period. Registering more than 5 patients when the list was short had an independent effect (rate ratio 0.61, CI 0.45-0.82). CONCLUSIONS: The number of registrants on a surgical wait list has an effect on the length of delay in providing necessary treatment. Our results suggest that a regulated list-length policy may contribute to reducing waiting times. Hospital managers may also use the findings to reduce uncertainty in reporting expected waits given the current list size, thereby improving resource planning.