Takaaki Saito

Association of a G994→T missense mutation in the plasma platelet-activating factor acetylhydrolase gene with risk of abdominal aortic aneurysm in Japanese

ObjectiveTo investigate a possible association with plasma platelet activating factor acetylhydrolase (PAF-AH) gene mutation with the risk of abdominal aortic aneurysm (AAA). Summary Background DataPlasma platelet activating factor acetylhydrolase is known to catalyze platelet activating factor (PAF), thereby inactivating its inflammatory function. Deficiency of this enzyme is caused by a missense mutation (G994 →T) in exon 9 of the plasma PAF-AH gene. MethodsWe did a case-control study including 131 patients (median age 73.4 [range 50–84] years) and 106 controls matched for age and sex. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF-AH activity was measured in both groups. ResultsThe frequency of the mutant allele (T allele) in the plasma PAF-AH gene in AAA patients was significantly higher than in control subjects. The association of the missense mutation with AAA was statistically significant and independent of other risk factors. Among AAA patients with normal genomic type, plasma PAF-AH activity was strongly correlated to the plasma concentration of low density lipoprotein cholesterol (LDL-C), while the correlation was not observed among AAA patients with heterozygotes genotype. Patients having AAA with both T allele and hyperlipidemia were more likely to have other atherosclerotic diseases such as ischemic heart disease, stroke and peripheral arterial occlusive diseases than patients with the normal genomic type and normal lipid level. ConclusionsThe genetic mutation of plasma PAF-AH gene appear to be an independent risk factor for AAA. Our findings need to be confirmed in a larger, prospective study including patients from different populations.

Superficial Thrombophlebitis of the Lower Limbs in Patients with Varicose Veins

AbstractPurpose. This study reviews 51 consecutive patients with superficial thrombophlebitis (STP) among 710 patients treated for varicose veins in our department. Methods. An assessment was made of various factors involved. Results. Of these 51 patients, 21 (41.1%) had systemic disorders, including 4 (7.8%) with malignant diseases. Six patients (11.8%) had deep vein thrombosis (DVT) and five (9.8%) had pulmonary embolism (PE). All of the patients with DVT and/or PE had a thrombus in either the greater saphenous vein or the lesser saphenous vein; however, none of the patients with STP and a thrombus in the distal saphenous branch had either DVT or PE. The levels of coagulofibrinolytic markers such as fibrin degradation product-D dimer, plasmin α2 plasmin inhibitor complex, and thrombin antithrombin III complex were elevated in patients with STP or DVT, compared with those with varicose veins only. The level of C-reactive protein (CRP) was also elevated in the patients with STP or DVT. These findings indicate that STP is not necessarily a localized disease, but may be a symptom of systemic disease. In addition to duplex scanning, the measurement of coagulofibrinolytic markers as well as CRP may be useful for detecting STP and/or DVT prior to the treatment of varicose veins.

Adventitial Vasa Vasorum Arteriosclerosis in Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a common disease among elderly individuals. However, the precise pathophysiology of AAA remains unknown. In AAA, an intraluminal thrombus prevents luminal perfusion of oxygen, allowing only the adventitial vaso vasorum (VV) to deliver oxygen and nutrients to the aortic wall. In this study, we examined changes in the adventitial VV wall in AAA to clarify the histopathological mechanisms underlying AAA. We found marked intimal hyperplasia of the adventitial VV in the AAA sac; further, immunohistological studies revealed proliferation of smooth muscle cells, which caused luminal stenosis of the VV. We also found decreased HemeB signals in the aortic wall of the sac as compared with those in the aortic wall of the neck region in AAA. The stenosis of adventitial VV in the AAA sac and the malperfusion of the aortic wall observed in the present study are new aspects of AAA pathology that are expected to enhance our understanding of this disease.

Virtual angioscopy using 3-dimensional rotational digital subtraction angiography for endovascular assessment.

Purpose: To investigate the feasibility of 3-dimensional rotational digital subtraction angiography (3D DSA) and the creation of virtual angioscopic images from its data before and after endovascular treatment. Technique: Data sets from 3D DSA studies were used to create intraluminal images simulating angioscopy for 36 patients with arterial stenosis, aneurysm, or endoleak after stent-graft deployment. A biplanar DSA unit was used to acquire rotational angiography data, which was then processed with a surface-rendering technique to create maximum intensity projections, shaded surface displays, multiplanar reconstructions, and virtual angioscopy. 3D reconstructions were created in 2 minutes after angiography and provided realistic views adequate for vessel measurement, morphology assessment, and endoleak evaluation. Conclusions: 3D DSA and virtual angioscopy are novel techniques that have been successful in recreating images of blood vessels immediately after angiography. These techniques could be useful as additional imaging modalities to complement computed tomography or magnetic resonance imaging in the evaluation of vascular diseases after endovascular therapy.

Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm.

The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30–49 mm in diameter) and in large AAAs (> 50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA.

Imaging Mass Spectrometry Reveals a Unique Distribution of Triglycerides in the Abdominal Aortic Aneurysmal Wall

The pathophysiology underlying abdominal aortic aneurysms (AAAs) remains unknown. In this study, we applied imaging mass spectrometry (IMS) to analyze the pathophysiology of the aneurysmal wall. Comparisons were performed between the tissue samples from the neck and the sac of the AAA, at a single time point, in 30 patients who underwent elective surgery of their AAAs. The localization of each lipid molecule in the aortic wall was assessed by IMS. Histopathological examination and IMS revealed a characteristic distribution of triglycerides (TGs) specifically in the aneurismal adventitia of the sac. This characteristic TG distribution was derived from an ectopic appearance of adipocytes in the adventitia. Furthermore, ectopic adipocyte accumulation in the aortic wall leads to the loss of the collagen fiber network subsequent to the wall rupture. The underlying mechanism of adipocyte accumulation involves the presence of adipose-derived stem cells (ADSCs) in the aneurismal adventitia and the expression of peroxisome proliferator-activated receptor gamma 2, a master regulator of adipocyte differentiation by some ADSCs. This study reveals new, previously overlooked aspects of AAA pathology.

Clinical Relationship Between Femoral Artery Aneurysms and Arteriomegaly

Abstract.Purpose: The purpose of this study was to determine the incidence of arteriomegaly in patients with femoral artery aneurysms (FAAs), and assess the differences in clinical characteristics between patients with and without arteriomegaly. Methods: We retrospectively analyzed 11 patients with a collective total of 16 true FAAs treated at our hospital between 1980 and 2000. The diagnosis of FAAs and arteriomegaly was made by angiography, ultrasonography, and computed tomography. Results: All 11 patients were men, 7 of whom had arteriomegaly with multiple aneurysms, including 1 abdominal aortic aneurysm, 5 iliac artery aneurysms, 5 contralateral FAAs, and 2 popliteal artery aneurysms. Aneurysmal multiplicity was not seen in the other 4 patients who had no evidence of arteriomegaly. Three patients in the nonarteriomegaly group were complicated by atherosclerotic occlusive disease of the lower extremities. Resection and arterial reconstruction was performed for 12 aneurysms; resection for 1, wrapping for 1, and exclusion for 2. One patient who underwent exclusion of an aneurysm suffered rupture of the aneurysm 1 year after the initial operation. Conclusion: A high incidence of multiple aneurysms was seen among patients with FAA, and all of those with arteriomegaly had multiple aneurysms. This suggests the need for a rationale to assess aneurysmal diseases for patients with arteriomegaly.

Intraperitoneal administration of hyperbarically oxygenated perfluorochemical enhances preservation of intestinal mucosa against ischemia/reperfusion injury.

ABSTRACT Perfluorochemicals (PFCs) have a high solubility for oxygen. We have previously demonstrated the effect of peritoneal lavage with oxygenated PFC (O2-PFC) on ameliorating ischemia/reperfusion (I/R)-induced intestinal ischemic damage in an animal model. In this study, we applied hyperbarically O2-PFC (HBO-PFC) to investigate whether a larger amount of oxygen carried by PFC could enhance the protective effect of O2-PFC during intestinal malperfusion. Rats were subjected to ischemia by clamping the superior mesenteric artery (SMA) for 90 min. The SMA was then declamped. Rats were divided into four groups. In group A, only anesthesia and abdominal incision were performed. In group B, SMA was clamped without O2-PFC. In group C, during the SMA clamp, 1 atm O2-PFC was injected into the abdominal cavity. In group D, 5 atm O2-PFC (HBO-PFC) was prepared using a custom-made hyperbaric oxygen tank and administered to the abdominal cavity during the SMA clamp. Ileal tissue adenosine triphosphate (ATP) levels 90 min after SMA declamping were determined using luciferase assay. To assess intestinal mucosal barrier function at 90 min after release of the SMA clip, everted gut sacs were prepared to measure the mucosal-to-serosal passage of fluorescein-conjugated dextran (FD4, molecular weight = 4 kDa). Thirty minutes after i.p. administraton, partial pressure of oxygen in HBO-PFC remained around 1000 mmHg, whereas partial pressure of oxygen in 1 atm O2-PFC decreased to around 400 mmHg. The intestinal tissue ATP was significantly preserved in group D. Moreover, the mucosal hyperpermeability of the gut sac after I/R was significantly ameliorated in group D. Hyperbarically oxygenated perfluorochemical might supply a larger amount of oxygen to ischemic tissue during SMA clamp, which protected the small intestine from I/R injury, possibly caused by the maintenance of tissue ATP levels during ischemia.

Videodensitometric blood flow analysis of abdominal aortic aneurysm and intravascular coagulation

OBJECTIVE We investigated the relation between flow pattern in abdominal aortic aneurysm (AAA) and intravascular coagulopathy characterized by increased fibrin degradation product d-dimer (FDP-DD) or thrombin-antithrombin complex (TAT). Materials and methods The ratio of AAA maximum endoluminal diameter (diameter of flow channel) (n = 23) to diameter of the aorta between the superior mesenteric and renal arteries (R ratio) was measured with three-dimensional computed tomography angiography. Digital subtraction angiography was performed with 20 mL (10 mL/s) of contrast agent injected from the suprarenal portion of the abdominal aorta. The duration between the time when average gray scale in the AAA reached maximum and average region of interest gray scale decreased to half-maximum (bolus transit time in AAA [BTT(AAA)]) was calculated. RESULTS Single correlation coefficient with statistic significance was detected between R ratio and BTT(AAA) (BTT(AAA) = 2.54 x R ratio + 3.65; r(2) =.30; P =.042). Among the three-dimensional morphologic and videodensitometric variants, BTT(AAA) was the most determinant factor associated with FDP-DD (FDP-DD = - 8.647 + 2.029 x BTT(AAA); r(2) =.448; P =.005). The most efficient predictors for TAT were maximum AAA endoluminal diameter (R(endomax)) and BTT(AAA) (TAT = - 14.007 + 2.102 x BTT(AAA) + 0.296 x R(endomax), r(2) =.360; P =.0069). CONCLUSIONS Our findings suggest a close link between abnormal flow pattern in AAA and activation of the coagulation-fibrinolysis system. Videodensitometric blood flow analysis can be useful in investigation of the pathophysiology of phenomena related to abnormal flow field in AAA.

Effects of Compression Stockings on Elevation of Leg Lymph Pumping Pressure and Improvement of Quality of Life in Healthy Female Volunteers: A Randomized Controlled Trial

Abstract Background: Lymph is pumped through the collecting lymphatic vessels by both intrinsic and extrinsic forces. The intrinsic pump relies on spontaneous lymphatic contraction, which generates the pumping lymph pressure (Plp). Among healthy people with daily leg edema, a considerable number of cases are accompanied with low leg Plp. Herein, a double-blinded controlled trial was conducted in healthy female volunteers with reduced leg Plp to compare the effectiveness of a 15–29 mmHg compression stocking (Stocking A) and a 8–16 mmHg stocking (Stocking B) on elevating Plp. Method and Results: Among 219 healthy female volunteers who underwent measurement of leg Plp, 80 participants (36.5%) had unilateral or bilateral legs with Plp < 20 mmHg (122 legs with Plp < 20 mmHg and 38 legs with Plp ≧ 20 mmHg). These 80 participants were assigned to wear either Stocking A (n = 40) or Stocking B (n = 40) for 16 weeks. Leg Plp was measured using indocyanine green fluorescence lymphography and an occlusion cuff technique while sitting. At 16 weeks, both Stockings A and B resulted in significantly elevated leg Plp, with the effect on elevating Plp being superior for Stocking A. Only Stocking A resulted in decreased prevalence of leg edema and improved Short Form-36 scores. Conclusion: Compression stockings may represent a therapeutic option to elevate leg Plp and ameliorate leg edema, thereby leading to improved quality of life in healthy females with low leg Plp.