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The operative records of 2816 patients undergoing repair for abdominal aortic aneurysm (AAA) from 1955 to 1985 were reviewed. Inflammatory aortic or iliac aneurysms were present in 127 patients (4.5%), 123 men and four women. Most patients were heavy smokers (92.1%). Clinical evidence of peripheral arterial occlusive disease and coronary artery disease was found in 26.6% and 39.4%, respectively. Additional aneurysms occurred in half of the patients; iliac aneurysms were the most common (55 patients), followed by thoracic or thoracoabdominal (17 patients), femoral (16 patients), and popliteal aneurysms (10 patients). Ultrasound and computed tomography suggested the diagnosis in 13.5% and 50%, respectively; angiography was not helpful. Excretory urographic findings of medial ureteral displacement or obstruction suggested the diagnosis in 31.4%. The aneurysm was repaired in 126 patients. Only one patient experienced acute aneurysm rupture, but eight patients had chronic contained leakage. When compared with patients who have ordinary atherosclerotic aneurysms, patients with inflammatory aneurysms are significantly more likely to have an elevated erythrocyte sedimentation rate (ESR, 73% vs. 33%, p less than 0.0001); weight loss (20.5% vs. 10%, p less than 0.05); symptoms (66% vs. 20%, p less than 0.0001); and an increased operative mortality rate (7.9% vs. 2.4%, p less than 0.002). The triad of chronic abdominal pain, weight loss, and elevated ESR in a patient with an abdominal aortic aneurysm is highly suggestive of an inflammatory aneurysm and may be beneficial in the preoperative preparation of the patient for aneurysm repair.

N. Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension. Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca 2ϩ levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca 2ϩ -activated ClϪ channels (Cl Ca), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of Cl Ca channels in PH was investigated using the monocrotaline (MCT)-induced PH model in the rat. Three weeks postinjection with a single dose of MCT (50 mg/kg ip), the animals developed right ventricular hypertrophy (heart weight measurements) and changes in pulmonary arterial flow (pulse-waved Doppler imaging) that were consistent with increased pulmonary arterial pressure and PH. Whole cell patch experiments revealed an increase in niflumic acid (NFA)-sensitive Ca 2ϩ -activated Cl Ϫ current [ICl(Ca)] density in PASMCs from large conduit and small intralobar pulmonary arteries of MCT-treated rats vs. aged-matched saline-injected controls. Quantitative RT-PCR and Western blot analysis revealed that the alterations in I Cl(Ca) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for Cl Ca channels. The contraction to serotonin of conduit and intralobar pulmonary arteries from MCT-treated rats exhibited greater sensitivity to nifedipine (1 M), an L-type Ca 2ϩ channel blocker, and NFA (30 or 100 M, with or without 10 M indomethacin to inhibit cyclooxygenases) or T16A Inh-A01 (10 M), TMEM16A/Cl Ca channel inhibitors, than that of control animals. In conclusion, augmented Cl Ca/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of PA in this model of PH. TMEM16A-encoded channels may therefore represent a novel therapeutic target in this disease. pulmonary arterial tone; TMEM16A; anoctamin-1; Ca 2ϩ -activated Cl Ϫ channel; patch-clamp technique PULMONARY HYPERTENSION (PH) is defined as a sustained high blood pressure (Ͼ25 mmHg at rest and Ͼ30 mmHg during exercise) in the main pulmonary artery (PA) that ultimately leads to failure of the right hand side of the heart and death (4). Characteristic pathophysiological manifestations of PH are enhanced vasoconstriction, thickening of the arterial muscle wall, and a propensity for thrombosis, as a result of changes in all layers of the blood vessel, but little is known about the molecular mechanisms that drive these pathological responses. It is well established that pulmonary arterial smooth muscle cells (PASMCs) from animal models of PH and human PH patients are more depolarized and exhibit a higher intracellular calcium concentration ([Ca 2ϩ ] i ) than cells from healthy individuals and several ionic conductances are altered in PASMCs from animal models of PH and PH patients (4,13,29,43,68,70). Except for one recent study carried out using the chronic hypoxic model of PH in the rat (58), there is little information regarding the potential role of Ca 2ϩ -activa...