Portal Hypertension Due to a Traumatic Arteriovenous Fistula in a Patient With a Celiac Artery Aneurysm.

This article describes a rare case of a traumatic splenic arteriovenous fistula (AVF) causing portal hypertension in a patient presenting with abdominal pain, diarrhea, and melena. A 78-year-old was admitted to the hospital with abdominal pain. The patient's history was notable for prior laparotomy and left nephrectomy for a gunshot wound. Workup demonstrated portal hypertension with a dilated splenic vein with aneurysmal changes and a saccular celiac artery aneurysm. Celiac angiogram demonstrated a communication between celiac and portal circulation. The patient underwent laparotomy with ligation of the splenic artery and resection of the celiac artery aneurysm. In conclusion, splenic AVFs are relatively rare in clinical practice. Once the diagnosis is established, operative intervention is required to avoid complications of portal hypertension. Surgical ligation has been used in this case with a successful outcome.

Fibrinogen and catheter-directed thrombolysis.

Fibrinogen is a complex glycoprotein that is known to play a significant role in the process of thrombus formation and evolution, and has been linked to the pathophysiology of atherosclerosis. Given the importance of fibrinogen in these processes, it has been evaluated as a biomarker for atherosclerotic disease and as a marker during treatment for venous and arterial thrombosis. Here we describe the expansive role that fibrinogen plays in human physiology.

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice.

Changes in dietary sodium intake are associated with changes in vascular volume and reactivity that may be mediated, in part, by alterations in endothelial nitric oxide synthase (eNOS) activity. Caveolin-1 (Cav-1), a transmembrane anchoring protein in the plasma membrane caveolae, binds eNOS and limits its translocation and activation. To test the hypothesis that endothelial Cav-1 participates in the dietary sodium-mediated effects on vascular function, we assessed vascular responses and nitric oxide (NO)-mediated mechanisms of vascular relaxation in Cav-1 knockout mice (Cav-1-/-) and wild-type control mice (WT; Cav-1+/+) placed on a high-salt (HS; 4% NaCl) or low-salt (LS; 0.08% NaCl) diet for 16 days. After the systolic blood pressure was measured, the thoracic aorta was isolated for measurement of vascular reactivity and NO production, and the heart was used for measurement of eNOS expression and/or activity. The blood pressure was elevated in HS mice treated with NG-nitro-l-arginine methyl ester and more so in Cav-1-/- than WT mice and was significantly reduced during the LS diet. Phenylephrine caused vascular contraction that was significantly reduced in Cav-1-/- (maximum 0.25 +/- 0.06 g/mg) compared with WT (0.75 +/- 0.22 g/mg) on the HS diet, and the differences were eliminated with the LS diet. Also, vascular contraction in response to membrane depolarization by high KCl (96 mM) was reduced in Cav-1-/- (0.27 +/- 0.05 g/mg) compared with WT mice (0.53 +/- 0.12 g/mg) on the HS diet, suggesting that the reduced vascular contraction is not limited to a particular receptor. Acetylcholine (10(-5) M) caused aortic relaxation in WT mice on HS (23.6 +/- 3.5%) and LS (23.7 +/- 5.5%) that was enhanced in Cav-1-/- HS (72.6 +/- 6.1%) and more so in Cav-1-/- LS mice (93.6 +/- 3.5%). RT-PCR analysis indicated increased eNOS mRNA expression in the aorta and heart, and Western blots indicated increased total eNOS and phosphorylated eNOS in the heart of Cav-1-/- compared with WT mice on the HS diet, and the genotypic differences were less apparent during the LS diet. Thus Cav-1 deficiency during the HS diet is associated with decreased vasoconstriction, increased vascular relaxation, and increased eNOS expression and activity, and these effects are altered during the LS diet. The data support the hypothesis that endothelial Cav-1, likely through an effect on eNOS activity, plays a prominent role in the regulation of vascular function during substantial changes in dietary sodium intake.

Experimental benefits of sex hormones on vascular function and the outcome of hormone therapy in cardiovascular disease.

Cardiovascular disease (CVD) is more common in men and postmenopausal women than premenopausal women, suggesting vascular benefits of female sex hormones. Experimental data have shown beneficial vascular effects of estrogen including stimulation of endothelium-dependent nitric oxide, prostacyclin and hyperpolarizing factor-mediated vascular relaxation. However, the experimental evidence did not translate into vascular benefits of hormone replacement therapy (HRT) in postmenopausal women, and HERS, HERS-II and WHI clinical trials demonstrated adverse cardiovascular events with HRT. The lack of vascular benefits of HRT could be related to the hormone used, the vascular estrogen receptor (ER), and the subject's age and preexisting cardiovascular condition. Natural and phytoestrogens in small doses may be more beneficial than synthetic estrogen. Specific estrogen receptor modulators (SERMs) could maximize the vascular benefits, with little side effects on breast cancer. Transdermal estrogens avoid the first-pass liver metabolism associated with the oral route. Postmenopausal decrease and genetic polymorphism in vascular ER and post-receptor signaling mechanisms could also modify the effects of HRT. Variants of cytosolic/nuclear ER mediate transcriptional genomic effects that stimulate endothelial cell growth, but inhibit vascular smooth muscle (VSM) proliferation. Also, plasma membrane ERs trigger not only non-genomic stimulation of endothelium-dependent vascular relaxation, but also inhibition of [Ca(2+)]i, protein kinase C and Rho kinase-dependent VSM contraction. HRT could also be more effective in the perimenopausal period than in older postmenopausal women, and may prevent the development, while worsening preexisting CVD. Lastly, progesterone may modify the vascular effects of estrogen, and modulators of estrogen/testosterone ratio could provide alternative HRT combinations. Thus, the type, dose, route of administration and the timing/duration of HRT should be customized depending on the subject's age and preexisting cardiovascular condition, and thereby make it possible to translate the beneficial vascular effects of sex hormones to the outcome of HRT in postmenopausal CVD.

Matrix metalloproteinase 2-induced venous dilation via hyperpolarization and activation of K+ channels: relevance to varicose vein formation.

BACKGROUND: Varicose veins are a common disorder of extensive venous dilation and remodeling with an as-yet unclear mechanism. Studies have shown increased plasma and tissue levels of matrix metalloproteinases (MMPs) in human varicose veins and animal models of venous hypertension. Although the effects of MMPs are generally attributed to extracellular matrix degradation, their effects on the mechanisms of venous contraction/relaxation are unclear. Our preliminary experiments have demonstrated that MMP-2 causes inhibition of phenylephrine-induced venous contraction. The purpose of this study was to determine whether MMP-induced inhibition of venous contraction involves an endothelium-dependent and/or -independent pathway. METHODS: Circular segments of the inferior vena cava (IVC) were isolated from male Sprague-Dawley rats and suspended between two wire hooks in a tissue bath, and the effects of MMP-2 on phenylephrine- and KCl-induced contraction were measured. To study the role of endothelium-derived vasodilators, experiments were performed in the presence and absence of endothelium; N(G)-l-nitro-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis; indomethacin, an inhibitor of prostacyclin synthesis; cromakalim, an activator of adenosine triphosphate-sensitive K+ channels (K(ATP)); and iberiotoxin, a blocker of large-conductance Ca2+-dependent K+ channels (BK(Ca)) and smooth muscle hyperpolarization. RESULTS: In endothelium-intact IVC segments, phenylephrine (10(-5) mol/L) caused significant contraction that slowly declined to 82.0% in 30 minutes. The addition of MMP-2 (1 microg/mL) caused a gradual decrease of phenylephrine contraction to 39.5% at 30 minutes. In endothelium-denuded IVC, MMP-2 induced a greater reduction of phenylephrine contraction, to 7.6%. In the presence of L-NAME (10(-4) mol/L), MMP-2 caused a marked decrease in phenylephrine contraction, to 4.4%. Large MMP-2-induced inhibition of phenylephrine contraction was also observed in IVC treated with L-NAME plus indomethacin. MMP-2 caused relaxation of phenylephrine contraction in IVC pretreated with cromakalim (10(-7) mol/L), an activator of K(ATP) channels. MMP-2-induced inhibition of phenylephrine contraction was abrogated in the presence of iberiotoxin (10(-8) mol/L), a blocker of BK(Ca). MMP-2 did not inhibit venous contraction during membrane depolarization by 96 mmol/L KCl, a condition that prevents outward K+ conductance and cell hyperpolarization. CONCLUSIONS: MMP-2 causes significant IVC relaxation that is potentiated in the absence of endothelium or during blockade of endothelium-mediated nitric oxide and prostacyclin synthesis. The lack of effects of MMP-2 on KCl contraction and in iberiotoxin-treated veins suggests MMP-2-induced smooth muscle hyperpolarization and activation of BK(Ca) channels--a novel effect of MMP that may play a role in the early stages of venous dilation and varicose vein formation.