Kazunori Inuzuka

Quantitative Lymph Imaging for Assessment of Lymph Function using Indocyanine Green Fluorescence Lymphography

OBJECTIVES A new diagnostic imaging technique that can assess lymph function is needed as a screening test in daily practice. This study assessed the use of indocyanine green (ICG) fluorescence lymphography in subjects without leg oedema. METHODS 0.3ml of ICG (0.5 %) was injected subcutaneously at the dorsum of the foot. Subsequently, the movement of ICG dye from the injection site to the groin was traced by visualizing its fluorescence signal with an infrared light camera. The time for the dye to reach the knee and groin were measured (Transit time to knee: TT(K), Transit time to groin: TT(G)). TT(G) was measured while standing, lying at a supine position, standing with massage, and sitting while using a cycle ergometer exercise at an intensity of 50W at 50rpm in ten healthy volunteers at intervals of 14 days. RESULTS Mean TT(G) during standing was 357+/-289 and 653+/-564 seconds for the right and left legs respectively. Compared to TT(G) in the standing position, all other conditions shortened TT(G). In another seventeen subjects without leg oedema, we compared transit time obtained with ICG fluorescence lymphography to that with dynamic lymphoscintigraphy. A significant correlation between transit time measured with ICG lymphography and dynamic lymphoscintigraphy was identified (r(2)=0.64, p<0.01). CONCLUSIONS ICG fluorescence lymphography has the potential to become an alternative lymphatic imaging technique to assess lymph function.

Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion.

Pancreatic enzymes in the ischemic intestine are involved in the production of in vivo inflammatory mediators. These mediators stimulate cells in the cardiovascular system during shock and initiate multiorgan failure. An important aspect that controls the extent of the inflammation is the dispersion of these mediators from the ischemic intestine. In the past, two pathways for dispersion of these inflammatory mediators have been identified, absorption into the intestinal venous circulation and uptake into the lymphatics. We hypothesize here that the inflammatory mediators produced by pancreatic digestive enzymes in the lumen of the intestine may also be released directly into the peritoneal space. To assess the presence of inflammatory mediators in the peritoneal cavity in response to splanchnic arterial occlusion (90 min) and reperfusion (SAO shock), we measured the ability of fluid collected from this cavity to activate naïve donor granulocytes. After SAO in control rats, peritoneal lavage fluid caused activation of naïve donor granulocytes when tested in vitro. In contrast, when the lumen of the small intestine was flushed with a broad-acting pancreatic enzyme inhibitor (6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate), the fluid no longer caused leukocyte activation. Reduction of the levels of inflammatory mediators in the peritoneal fluid was associated with an attenuation in the fall of blood pressure after SAO shock. These results indicate that the inflammatory mediators, which are produced by pancreatic digestive enzymes, can be absorbed directly into the systemic circulation via a transperitoneal route and play a part in the development of multiorgan failure.

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.

Lymphangiogenesis and Angiogenesis in Abdominal Aortic Aneurysm

The pathogenesis of abdominal aortic aneurysm (AAA) is characterized to be inflammation-associated degeneration of vascular wall. Neovascularization is regularly found in human AAA and considered to play critical roles in the development and rupture of AAA. However, little is known about lymphangiogenesis in AAA. The purpose of this study was to demonstrate both angiogenesis and lymphangiogenesis in AAA. Abdominal aortic tissue was harvested either from autopsy (control group) and during open-repair surgery for AAA (AAA group). Adventitial lymphatic vasa vasorum was observed in both groups, but seemed to be no significant morphological changes in AAA. Immunohistochemical studies identified infiltration of lymphatic vessel endothelial hyaluronan receptor (LYVE) −1, vascular endothelial growth factor (VEGF)-C, and matrix metalloproteinase (MMP)-9-positive macrophages and podoplanin and Prox-1-positive microvessels in the intima/media in AAA wall, where hypoxia-inducible factors (HIF)-1α was expressed. VEGF-C and MMP-9 were not expressed in macrophages infiltrating in the adventitia. Intraoperative indocyanine green fluorescence lymphography revealed lymph stasis in intima/medial in AAA. Fluorescence microscopy of the collected samples also confirmed the accumulation of lymph in the intima/media but not in adventitia. These results demonstrate that infiltration of macrophages in intima/media is associated with lymphangiogenesis and angiogenesis in AAA. Lymph-drainage appeared to be insufficient in the AAA wall.

Laparoscopic Nephrectomy, Ex Vivo Repair, and Autotransplantation for a Renal Artery Aneurysm : Report of a Case

A 57-year-old woman was hospitalized with a left renal artery aneurysm (RAA). The aneurysm measured 35 mm in diameter and was located at the renal artery bifurcation. We performed a laparoscopic nephrectomy using a retroperitoneal approach and performed an ex vivo repair of the renal artery. The reconstructed kidney was then autotransplanted at the left iliac fossa. The patients postoperative course was uneventful. A laparoscopic nephrectomy and ex vivo repair are both considered to be effective for treating complex RAA.

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.

Hemorrhagic Shock with Delayed Retroperitoneal Hemorrhage After Deployment of an Inferior Vena Cava Filter: Report of a Case

Although inferior vena cava (IVC) filter placement has demonstrated an excellent therapeutic efficacy in preventing pulmonary embolism, several filter-related complications have been reported. Among them, retroperitoneal hemorrhage due to IVC perforation is one of the most serious complications. We report herein a female patient who underwent TrapEase IVC filter placement with anticoagulation and thrombolytic therapy for treatment of pulmonary embolism, and later demonstrated hemorrhagic shock 5 days after filter placement. The patients blood pressure stabilized after the anticoagulant therapy was stopped and she received a blood transfusion. We should therefore carefully observe patients after IVC filter placement, particularly those receiving simultaneous anticoagulation therapy.

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.

Characteristic Distribution Pattern of Lysophosphatidylcholine in Fibromuscular Dysplasia-Associated Visceral Artery Aneurysms Compared with Atherosclerotic Visceral Artery Aneurysms

AIM Asymptomatic visceral artery aneurysms (VAAs) have increasingly been found, with most being either atherosclerotic VAAs or fibromuscular dysplasia (FMD)-associated VAAs. However, little is known about the pathogenesis of both diseases. We aimed to identify the differences in the distribution pattern of lipid molecules between atherosclerotic VAAs and FMD-associated VAAs. METHODS We conducted a histological study of VAAs using imaging mass spectrometry (IMS) to assess the accumulation of lipid molecules in both the aneurysmal sac and the adjacent arteries without aneurysmal changes in 17 VAA samples, which were resected during the surgery. RESULTS IMS revealed characteristic distributions of cholesterol ester in intima and media in the atherosclerotic VAAs, which was hardly detected in FMD-associated VAAs. However, lysophosphatidylcholine (lysoPC), a proinflammatory and proapoptotic lipid mediator, was accumulated in the medial ridge of the adventitia of FMD-associated in the aneurysmal sac, and it was also diffusely accumulated in the adjacent arteries. In contrast, lysoPC was accumulated in the area of intimal hyperplasia in atherosclerotic VAAs and the adjacent arteries. CONCLUSION The distribution patterns of lipid molecules were different between the FMD-associated and atherosclerotic VAAs. The diffuse accumulation of lysoPCs in the visceral arteries may be a predisposition for the formation of FMD-associated VAAs.

Automated Bedside Measurement of Penile Blood Flow Using Pulse-Volume Plethysmography

PurposeTo evaluate the efficiency of the form PWV/ABI (pulse wave velocity/ankle brachial pressure index) for measuring penile blood pressure (PBP) and the penile brachial pressure index (PBI).MethodsWe measured PBP and the PBI using both form PWV/ABI and Doppler ultrasonography in 40 men with surgical disorders.ResultsBy using pulse-volume recording, the form PWV/ABI can simultaneously measure PBP and bilateral brachial artery pressure, and calculate the PBI automatically. The data obtained showed strong correlations with those obtained by the conventional Doppler ultrasound technique. Moreover, measurements were completed within 5 min at the bedside and the data were stored in the devices memory.ConclusionThe form PWV/ABI is a useful tool for assessing pelvic hemodynamics and diagnosing vasculogenic impotence.