Endothelial function is preserved in pregnant women with well-controlled type 1 diabetes

Objective Pregnant women with diabetes mellitus have a higher incidence of adverse pregnancy outcomes. Vascular, and in particular, endothelial function may be significantly modified in diabetes resulting in impaired endothelium-dependent relaxation. This study aims to investigate endothelium-dependent relaxation in pregnant women with pre-existing type 1 diabetes mellitus.
Methods Small arteries (mean luminal diameter ∼295 μm) were isolated from biopsies of subcutaneous fat from pregnant women with pre-existing type 1 diabetes mellitus, non-diabetic pregnant women, and non-diabetic non-pregnant women. Endothelial and smooth muscle function were determined using wire myography, and the contributions of nitric oxide, vasodilator prostanoid and endothelial hyperpolarisation were studied using specific inhibitors.
Results Arteries obtained from the diabetic pregnant women did not demonstrate any difference in either endothelial or smooth muscle function when compared with non-diabetic pregnant women. The contribution of nitric oxide to endothelium-dependent relaxation was ∼20% in the pregnant women regardless of whether they were diabetic, and ∼11% in the non-pregnant women. Endothelial hyperpolarisation appeared to contribute largely to vasorelaxation in human subcutaneous arteries, and was at least twice that of nitric oxide in pregnant women and fivefold greater in non-pregnant women.
Conclusions This study provides evidence that pregnant women with well-controlled pre-existing type 1 diabetes mellitus have both normal endothelial and smooth muscle function. Endothelium-dependent hyperpolarisation appears to play a large role in vascular relaxation in human subcutaneous resistance arteries. This study suggests that the problems associated with diabetic pregnancies are unlikely to be due to vascular dysfunction.     

Simple technique to ensure coaxial guidewire positioning for placement of iliac limb of modular aortic endograft

Endovascular abdominal aortic aneurysm repair using a modular bifurcated stent-graft requires the initial placement of the main component in the infrarenal aorta, followed by insertion of additional iliac stent-graft(s) to exclude aneurysm and to securely affix the device. Placement of the contralateral iliac component within the main bifurcated device is critical in this endovascular procedure, as malpositioning of the contralateral iliac limb can require conversion to open aneurysm repair. A simple adjunctive technique utilizing a rotational maneuver of a pigtail catheter is described. This maneuver reliably confirms the proper placement of the contralateral iliac stent-graft within the main bifurcated device.     

Reversal of Transjugular Intrahepatic Portosystemic Shunt (TIPS)-Induced Hepatic Encephalopathy Using a Strictured Self-Expanding Covered Stent

Hepatic encephalopathy is a known complication following percutaneous transjugular intrahepatic portosystemic shunt (TIPS) placement. We describe herein a simple and effective strategy of TIPS revision by creating an intraluminal stricture within a self-expanding covered stent, which is deployed in the portosystemic shunt to reduce the TIPS blood flow. This technique was successful in reversing a TIPS-induced hepatic encephalopathy in our patient. An erratum to this article can be found at .     

HIV protease inhibitor ritonavir induces endothelial dysfunction in porcine arteries

Introduction: Although HIV Protease inhibitors significantly reduce the viral load, they may be associated with increased risk of cardiovascular disease. The aim of this study was to investigate the effects of HIV protease inhibitor ritonavir on endothelial cell function. Methods: Porcine carotid arteries were perfusion cultured for 24 hours without or with a clinically relevant dose of 15 μM of ritonavir. Subsequently, vessels were pre-contracted with norepinephrine followed by relaxation with graded doses of acetylcholine. Vessel diameters were determined with video imaging. Rings of vessels were cultured without or with ritonavir for 24 hours and subsequently basal and NADPH induced superoxide levels were determined using lucigenin enhanced chemiluminescence. Immunohistochemical staining for nitrotyrosine was also used to demonstrate oxidative stress. Results: Vessel contraction was reduced from 19 ± 3 % in control vessels (n = 12) to 9.9 ± 2.7% in ritonavir treated vessels (n = 11, P < 0.05). Endothelial dependent relaxation was also significantly reduced by 72%, 62%, and 65% in response to 10⁻⁹, 10⁻⁷, and 10⁻⁵ M concentrations of acetylcholine, respectively, in ritonavir treated vessels compared to controls (P < 0.005). There was a significant 56% increase in basal superoxide production (n = 7, P < 0.02) and a significant 40% increase in superoxide production (n = 8, P < 0.01) with addition of NADPH in vessel rings treated with ritonavir compared to control vessels. Diphenyleneiodonium Chloride (NAD(P)H oxidase inhibitor) and Tiron (cell permeable superoxide scavenger) significantly reduced superoxide production in ritonavir treated vessels. Nitrotyrosine immunoreactivity was increased in ritonavir treated vessels compared to controls. Conclusions: These data demonstrate that HIV protease inhibitor ritonavir causes a significant reduction in endothelium-dependent vasorelaxation in cultured porcine carotid arteries. Ritonavir also significantly increases superoxide levels, which may be resulted from increased NAD(P)H oxidase activity.     

Red wine prevents homocysteine-induced endothelial dysfunction in porcine coronary arteries

BACKGROUND: Hyperhomocysteinemia is an independent risk factor of coronary artery disease. Clinical studies have indicated that moderate red wine consumption is associated with a reduction of incidence of coronary artery disease. In this study, we determined the effect of red wine on homocysteine- induced endothelial dysfunction in porcine coronary arteries. MATERIALS AND METHODS: Porcine coronary arteries were dissected from 6 pig hearts and cut into 5-mm ring segments, which were assigned into 4 groups (9 rings/group): blank control, homocysteine treated (50 muM), red wine treated (0.08% alcohol), and homocysteine plus red wine treated. The rings were cultured in cell culture medium with or without treatment for 24 h. Myograph analysis was performed with U46619 (10(-7) M) for contraction and cumulative bradykinin (10(-9) to 10(-5) M) for endothelium-dependent relaxation. The endothelial nitric oxide synthase (eNOS) levels were analyzed by RT-PCR, Western blot, and immunohistochemistry. RESULTS: In response to 10(-5) M bradykinin, porcine coronary artery rings treated with homocysteine (50 muM) showed a significant reduction of endothelium-dependent vasorelaxation by 43% as compared to controls (P < 0.05). However, rings treated with red wine (0.08% alcohol) plus homocysteine showed no significant difference as compared to controls. Endothelium-dependent vasorelaxation was not different between control and red wine treated groups. Furthermore, eNOS mRNA density levels were significantly reduced by 36% in homocysteine treated group as compared to controls (P < 0.05). eNOS protein levels were also substantially reduced in the homocysteine-treated group. However, red wine treatment reversed the effect of homocysteine-induced eNOS downregulation. CONCLUSIONS: Homocysteine significantly impaired endothelial functions including endothelium-dependent vasorelaxation and eNOS mRNA and protein levels in porcine coronary arteries; and red wine effectively prevented homocysteine-induced endothelial dysfunction. This study suggests that protecting coronary endothelial cells from homocysteine damage may be an important mechanism of red wine for preventing coronary artery disease.     

Transluminal stent graft repair with Wallgraft endoprosthesis in a porcine arteriovenous graft pseudoaneurysm model

PURPOSE: Pseudoaneurysm is a known complication of arteriovenous grafts in chronic hemodialysis and can result in graft disruption or thrombosis if left untreated. This study evaluated the safety and efficacy of endovascular repair with Wallgraft endoprosthesis (Boston Scientific, Inc, Watertown, Mass) in a porcine arteriovenous graft (AVG) pseudoaneurysm model. Materials and Methods: Bilateral groin AVG pseudoaneurysms (n = 18) were created with an oversized Dacron interposition graft within a polytetrafluoroethylene femoral AVG in nine domestic swine and allowed to mature 28 +/- 4 days (standard deviation). Transluminal placement of Wallgraft was performed to exclude the pseudoaneurysm from the AVG circulation. Hemodialysis was performed (400 mL/min x 1 hour, with intravenous heparin 30 units/kg) every 4 days for a total of 6 weeks via 15-gauge needles in the treated AVG pseudoaneurysm site. Arteriography and duplex ultrasound scan were performed to determine AVG patency and pseudoaneurysm flow. Histologic evaluation was performed to determine Wallgraft morphology. In vitro pulsatile flow chamber was used to determine maximal flow volume without peri-Wallgraft endoleak. RESULTS: All AVG pseudoaneurysms were successfully excluded with the Wallgrafts. Twelve AVG (67%) remained patent at the completion of the study. No Wallgraft migration occurred from hemodialysis. Transient peri-Wallgraft endoleak (<2 hours after hemodialysis) was present in 13 of 18 (72%) and four of 12 (33%) AVG pseudoaneurysms by weeks 1 and 6, respectively. With maintenance of an intraluminal pressure of 80, 100, 120, 140, and 160 mm Hg in the pulsatile flow chamber, the maximal flow rates without peri-Wallgraft endoleak were 625 +/- 120, 650 +/- 145, 620 +/- 95, 425 +/- 110, and 262 +/- 86 mL/min. Scanning electron microscopy showed a neointimal layer covered with thrombus on the Wallgraft surface. CONCLUSION: Endoluminal placement of Wallgraft endoprosthesis provides adequate structural support for continuous hemodialysis after AVG pseudoaneurysm exclusion. Transient blood flow in the pseudoaneurysm cavity may occur immediately after the hemodialysis, which may represent the effect of heparin used during hemodialysis. This study suggests Wallgraft is a safe and effective treatment for AVG pseudoaneurysm and permits continuous hemodialysis.     

Delayed aortic aneurysm enlargement due to endotension after endovascular abdominal aortic aneurysm repair

Abdominal aortic aneurysm (AAA) enlarges after successful endovascular repair, because of persistent blood flow within the aneurysm sac, or endoleak. In the absence of detectable endoleak, AAA may still expand, in part because of persistent pressurization within the excluded aneurysm, or endotension. We report three patients who underwent successful endovascular AAA repair in whom postoperative surveillance showed aneurysm regression, yet delayed AAA enlargement without demonstrable endoleak developed in all three patients. Endotension was confirmed in all three patients at elective open conversion. Our study underscores the significance of endotension as a mechanism of delayed aneurysm enlargement after successful endovascular AAA repair.     

A prospective study of a hand-held ultrasound device in abdominal aortic aneurysm evaluation

PURPOSE: Effective treatment of abdominal aortic aneurysm (AAA) requires both early detection and timely repair to reduce aneurysm-related mortality. The purpose of this prospective study was to evaluate the utility of a hand-held ultrasonography (US) device in AAA screening in a Veterans Affairs vascular surgical service. METHODS: During a 16-month period, patients with risk factors for AAA were evaluated in a blinded fashion with a hand-held US device performed by physicians. A conventional abdominal duplex US examination was also performed by a certified vascular ultrasonographer. Results of the hand-held US was compared with the conventional duplex US examination. RESULTS: A total of 104 patients were evaluated (97 men, mean age 67 +/- 6.3 years). The mean times for hand-held and conventional duplex US examinations were 5.3 +/- 3.2 minutes and 3.1 +/- 2.4 minutes (not significant), respectively. Using the conventional duplex US as a reference, the sensitivity and specificity of the hand-held device in detecting a AAA were 93% and 97%, respectively. The positive and negative predictive values of the hand-held device were 89% and 98%, respectively. The likelihood ratios of positive and negative tests of the hand-held US device examination were 82 and 0.14, respectively. The diagnostic accuracy of the hand-held US device as compared with the conventional duplex US was 98%. CONCLUSIONS: A hand-held portable US device is effective and accurate in AAA screening with results comparable to the conventional abdominal duplex examination. Moreover, hand-held portable US for AAA screening can be performed expeditiously during physical examination. It should be used as an extension in routine physical examination in vascular patients.     

Impact of an endovascular program on the operative experience of abdominal aortic aneurysm in vascular fellowship and general surgery residency

BACKGROUND: This study was performed to determine the impact of an endovascular program (EVP) on open and endovascular abdominal aortic aneurysm (AAA) operations in a residency training institution. METHODS: Over an 8-year period ending in September 2001, hospital records of all patients undergoing open or endovascular AAA repair were retrospectively reviewed. Data were analyzed to determine the changing patterns of case volume, type of operative repair, and complexity of open repair with regards to the training of both general surgical chief residents and vascular fellows. RESULTS: A total of 849 AAA operations were performed during the study period. The initiation of the EVP in 1997 resulted in a steady increase in the total annual AAA cases (P < 0.05), due in part to an increase in endovascular AAA operations despite a decrease in the annual open AAA volume. EVP had a positive impact on the overall operative experience of vascular fellows owing to the large increase in their endovascular AAA experience (annual mean pre-EVP 3 +/- 0.8 versus post-EVP 47 +/- 9.6, P < 0.01). A significant reduction occurred in the vascular fellows' open AAA experience (annual mean pre-EVP 40 +/- 12.7 versus post-EVP 19 +/- 9.4, P < 0.05). EVP did not affect the endovascular AAA experience of general surgery chief residents (annual mean pre-EVP 1 +/- 0.8 versus post-EVP 3 +/- 1.5, not significant). A significant reduction occurred in chief residents' open AAA experience (annual mean pre-EVP 39 +/- 9.7 versus post-EVP 18 +/- 7.4, P < 0.05). EVP did not affect the operative experience of complex open AAA operations in either vascular fellows or general surgery residents. CONCLUSIONS: An endovascular program has a positive impact on the aortic aneurysm practice in an academic institution, as evidenced by the significant increase in annual endovascular AAA cases despite a decrease in open AAA operations. Although vascular fellows continued to maintain sufficient experience in both open and endovascular AAA operations, general surgery chief residents suffered a significant decrease in their open AAA experience. Further evaluation of the residency system is warranted to better optimize the training paradigm of both vascular fellowship and general surgery residency.