Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia.

Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH.

Endothelial arginase II: a novel target for the treatment of atherosclerosis.

Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic endothelial cells. Here, we demonstrate that vascular endothelial arginase activity is increased in atherogenic-prone apolipoprotein E-null (ApoE(-/-)) and wild-type mice fed a high cholesterol diet. In ApoE(-/-) mice, selective arginase II inhibition or deletion of the arginase II gene (Arg II(-/-) mice) prevents high-cholesterol diet-dependent decreases in vascular NO production, decreases endothelial reactive oxygen species production, restores endothelial function, and prevents oxidized low-density lipoprotein-dependent increases in vascular stiffness. Furthermore, arginase inhibition significantly decreases plaque burden. These data indicate that arginase II plays a critical role in the pathophysiology of cholesterol-mediated endothelial dysfunction and represents a novel target for therapy in atherosclerosis.

Prolonged pulmonary support after cardiac surgery: incidence, risk factors and outcomes: a retrospective cohort study.

BACKGROUND: Post-cardiac surgery pulmonary dysfunction may be underreported. Therefore, we evaluated associated risk factors for prolonged pulmonary support after cardiac surgery. METHODS AND MATERIALS: We conducted a retrospective, observational study of consecutive patients undergoing coronary artery bypass grafting or coronary artery bypass grafting plus valve repair/replacement between Jan 1, 2005, and Dec 31, 2010, at an academic medical center. Using multivariate logistic regression and Cox proportional hazards modeling, we identified risk factors associated with prolonged mechanical ventilation and supplemental O2 support as well as in-hospital mortality. RESULTS: Overall, 33% (1298/3881) of patients required more than 2 days of mechanical ventilation and/or more than 5 days of supplemental O2 (prolonged support). Independent risk factors included age, weight, pre-existing lung disease, cardiac or renal dysfunction, emergent status, transfusion and cardiopulmonary bypass duration. Prolonged support was associated with increased mortality (OR, 4.75; 95% CI, 2.95-7.95; P < .001). Radiological evidence of persistent pulmonary edema 2 days after surgery was found in 4% of controls and 27% of prolonged support cases. CONCLUSIONS: We identified risk factors for prolonged mechanical ventilation and supplemental O2 use, described an association with increased adverse outcomes, and determined that persistent pulmonary edema on day 2 was the most likely radiological finding.

Aneurisma isolado de artéria femoral superficial roto contido: relato de caso / Isolated ruptured aneurysm of the superficial femoral artery: case report

Aneurismas verdadeiros isolados da artéria femoral superficial (AFS) são eventos raros. Manifestam-se principalmente em homens idosos e frequentemente estão associados a outros aneurismas. Possuem etiologia variada e costumam ser detectados quando apresentam complicações como trombose, embolização distal ou, mais raramente, ruptura. O presente caso refere-se a um paciente cujo aneurisma de AFS se apresentou roto contido e sem associações com outros aneurismas. Foram realizados eco-Doppler colorido arterial, que diagnosticou a ruptura, e angiotomografia, que evidenciou aneurisma sacular de AFS medindo 11,4 × 8,8 cm, com grande trombo mural. Uma arteriografia foi utilizada para programação de revascularização, e detectou-se leito distal via artéria tibial anterior. O paciente foi submetido a revascularização cirúrgica convencional eletiva em artéria femoropoplítea distal com veia safena ipsilateral invertida, com sucesso. Apresentou como complicação pós-operatória infecção de sítio cirúrgico. A pesquisa microbiológica teve resultado negativo, e o estudo anatomopatológico confirmou aneurisma verdadeiro da AFS

Isolated true aneurysms of the superficial femoral artery (SFA) are rare events. They mostly manifest in elderly men and are frequently seen in conjunction with other aneurysms. They have varied etiology and are usually detected when they complicate with thrombosis or distal embolization, or, more rarely, when they rupture. The present case report describes a patient with an aneurysm of the SFA that was ruptured and contained and who had no other aneurysms. Color Doppler ultrasound of the arteries revealed the rupture and angiotomography showed a saccular aneurysm of the SFA measuring 11.4 × 8.8 cm, with a large mural thrombus. Arteriography was used to plan revascularization and showed the distal bed with outflow via the anterior tibial artery. The patient was treated with conventional elective distal femoropopliteal surgical revascularization with the ipsilateral saphenous vein inverted, which was successful. Recovery was complicated by a postoperative surgical site infection. Microbiology tests were negative and the anatomopathological study confirmed a true aneurysm of the SFA

Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats.

There is increasing evidence that upregulation of arginase contributes to impaired endothelial function in aging. In this study, we demonstrate that arginase upregulation leads to endothelial nitric oxide synthase (eNOS) uncoupling and that in vivo chronic inhibition of arginase restores nitroso-redox balance, improves endothelial function, and increases vascular compliance in old rats. Arginase activity in old rats was significantly increased compared with that shown in young rats. Old rats had significantly lower nitric oxide (NO) and higher superoxide (O2(-)) production than young. Acute inhibition of both NOS, with N(G)-nitro-l-arginine methyl ester, and arginase, with 2S-amino- 6-boronohexanoic acid (ABH), significantly reduced O2(-) production in old rats but not in young. In addition, the ratio of eNOS dimer to monomer in old rats was significantly decreased compared with that shown in young rats. These results suggest that eNOS was uncoupled in old rats. Although the expression of arginase 1 and eNOS was similar in young and old rats, inducible NOS (iNOS) was significantly upregulated. Furthermore, S-nitrosylation of arginase 1 was significantly elevated in old rats. These findings support our previously published finding that iNOS nitrosylates and activates arginase 1 (Santhanam et al., Circ Res 101: 692-702, 2007). Chronic arginase inhibition in old rats preserved eNOS dimer-to-monomer ratio and significantly reduced O2(-) production and enhanced endothelial-dependent vasorelaxation to ACh. In addition, ABH significantly reduced vascular stiffness in old rats. These data indicate that iNOS-dependent S-nitrosylation of arginase 1 and the increase in arginase activity lead to eNOS uncoupling, contributing to the nitroso-redox imbalance, endothelial dysfunction, and vascular stiffness observed in vascular aging. We suggest that arginase is a viable target for therapy in age-dependent vascular stiffness.

Mitochondrial arginase II constrains endothelial NOS-3 activity.

Emerging evidence supports the idea that arginase, expressed in the vascular endothelial cells of humans and other species, modulates endothelial nitric oxide (NO) synthase-3 (NOS-3) activity by regulating intracellular L-arginine bioavailability. Arginase II is thought to be expressed in the mitochondria of a variety of nonendothelial cells, whereas arginase I is known to be confined to the cytosol of hepatic and other cells. The isoforms that regulate NOS-3 and their subcellular distribution, however, remain incompletely characterized. We therefore tested the hypothesis that arginase II is confined to the mitochondria and that mitochondrial arginase II reciprocally regulates vascular endothelial NO production. Western blot analysis, immunocytochemistry with MitoTracker, and immunoelectron microscopy confirmed that arginase II is confined predominantly but not exclusively to the mitochondria. Arginase activity was significantly decreased, whereas NO production was significantly increased in the aorta and isolated endothelial cells from arginase II knockout (ArgII(-/-)) mice compared with wild-type (WT) mice. The vasorelaxation response to acetylcholine (ACh) was markedly enhanced and the vasoconstrictor response to phenylephrine (PE) attenuated in ArgII(-/-) in pressurized mouse carotid arteries. Furthermore, inhibition of NOS-3 by N(G)-nitro-L-arginine methyl ester (L-NAME) impaired ACh response and restored the PE response to that observed in WT vessels. Vascular stiffness, as assessed by pulse wave velocity (PWV), was significantly decreased in ArgII(-/-) compared with WT mice. On the other hand, 14 days of oral L-NAME treatment significantly increased PWV in both WT and ArgII(-/-) mice, such that they were not significantly different from one another. These data suggest that arginase II is predominantly confined to the mitochondria and that this mitochondrial arginase II regulates NO production, vascular endothelial function, and vascular stiffness by modulating NOS-3 activity.

Postnephrectomy arteriovenous fistula

The development of the postnephrectomy arteriovenous fistula (PNAVF) between the renal vessels stumps is rare. Here we present a case report of PNAVF, and review the diagnosis, treatment and prevention. The most common clinical features include a loud murmur over the previous nephrectomy scar, and heart failure resistant to common medical treatment. A 58-year-old white woman was admited to the hospital for a complete evaluation of an unexplained congestive heart failure with no respponse to common medical treatment. She had had a right nephrectomy for pynophrosis 13 years before. The diagnosis of PNAVF was suspected because over the right lumbar region a definite trill was palpated, and on auscultation a harsh, machinery-like murmur was heard. The diagnosis was confirmed by aortogram and selective renal arteriography. In May 1989, the right arteriovenous was excised through a right subcostal transperitoneal approach. The renal vessel stumps were individually ligated and sutured separately close to aorta and vena cava. The patient's postoperative course was entirely uneventful in the following seven years. We conclude that during nephrectomy, the renal vessels should be ligated separately, and the transfixation in mass of the stumps avoided to prevent arteriovenous fistula.

Anatomical study of the renal veins observed during 342 living-donor nephrectomies

The anatomical variations of renal veins observed during 342 nephrectomies in living donors are described, 311 cases on the left side and 31 on the right. The following anatomy of the renocava veins was observed: 1. On the left side the renal vein was always unique (311/311) and had two tributaries (suprarenal and gonadal veins) in 100 per cent and one or more renolumbar veins in 65.27 per cent, encircling the aorta in 1.07 per cent, was retroaortic in 1.4 per cent; and the inferior vena cava double in 0.64 per cent; B-on the right side the renal vein was double in 29 per cent (9/31) and had only one tributary (gonadal vein) in one case, for 3.22 per cent (1/31); three or more renal veins in 9.7 per cent (3/31). We concluded that the left renal vein is always unique, presenting variations principally in its tributaries and trajectory. On the right side, the renal vein was double or triple in 38.79 per cent.