Real-Time Assessment of Tissue Oxygen Saturation Using a Novel Oximeter During Revascularization for Acute Limb Ischemia: A Case Report.

Emergency surgery was performed to treat acute lower limb ischemia caused by heart thromboembolism and concomitant popliteal artery aneurysm. Using a near-infrared spectroscopy oximeter, regional tissue oxygen saturation (rSO2) was monitored to assess the tissue perfusion pre-, intra-, and postoperatively. rSO2 values did not increase sufficiently following thromboembolectomy of the superficial femoral artery, but they dramatically recovered after additional popliteal-anterior tibial bypass surgery. The affected limb was successfully salvaged. rSO2 monitoring was easily measured intraoperatively, which might be beneficial in evaluating tissue perfusion in patients with acute limb ischemia.

The Usefulness of a Three-Microneedle Device for Indocyanine Green Fluorescence Lymphography.

Background: Indocyanine green (ICG) fluorescence lymphography is widely used to diagnose lymphedema. There is little consensus on the appropriate injection method for ICG fluorescence lymphangiography. We used a three-microneedle device (TMD) for skin injection of ICG solution and investigated its usefulness. Methods and Results: Thirty healthy volunteers were injected with ICG solution using a 27-gauge (27G) needle in one foot and a TMD in the other foot. Injection-related pain was evaluated using the Numerical Rating Scale (NRS) and Face Rating Scale (FRS). The skin depth of the injected ICG solution was evaluated by injecting the solution into the skin of amputated lower limbs using a 27G needle or TMD using ICG fluorescence microscopy. The median and interquartile range of the NRS scores was 3 (3-4) and 2 (2-4) in the 27G needle and TMD groups, respectively; that of the FRS scores was 2 (2-3) and 2 (1-2) in the 27G needle and TMD groups, respectively. Injection-related pain was significantly lower with the TMD than with the 27G needle. The lymphatic vessels were similarly visible using both needles. The depth of the ICG solution varied for each injection with a 27G needle (400-1200 µm) and was consistent at ∼300-700 µm below the skin surface using the TMD. Injection depth was significantly different between the 27G needle and the TMD. Conclusions: Injection-related pain decreased using the TMD, and ICG solution depth was consistent on fluorescence lymphography. A TMD may be useful for ICG fluorescence lymphography. Clinical Trials Registry (UMIN-CTR; ID: UMIN000033425).

Survey of Food Intake in Patients with Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a vascular disease that involves asymptomatic progressive expansion of the abdominal aorta. Aneurysm rupture is associated with a high mortality rate. Dietary conditions may be associated with the development and rupture of AAA. However, the relationship between nutrition and AAA is not completely understood. In this study, a nutrition survey was conducted using a brief self-administered diet history questionnaire (BDHQ) to evaluate the relationship between AAA and dietary habits. One-hundred and twenty-six Japanese people participated in the nutrition survey. Food intake status was analyzed in four groups: the analyzed group-1 (all men), analyzed group-2 (men with smoking history), analyzed group-3 (all women) and analyzed group-4 (women without smoking history). In group-2 and group-3, the intake of citrus fruits was significantly lower in the AAA group than in the non-AAA group. In group-2, the intake of soybean and soybean products was significantly lower in the AAA group than in the non-AAA group. In analyzed group-3, the intake of other vegetables (vegetables except for green and yellow vegetables and soybeans) and seafood was significantly lower in the AAA group than in the non-AAA group. This study suggests that AAA onset may be associated with low intake of fruits, soybeans, vegetables, and seafood.

The Patency of Tibial/Peroneal Arteries Affects the Increment of Regional Tissue Saturation of Oxygen in Each Angiosome after Superficial Femoral Artery Revascularization.

Objective: The angiosome model is a controversial concept in the revascularization of patients with chronic limb-threatening ischemia (CLTI). The aim of this study was to demonstrate the importance of patency of the tibial/peroneal arteries for regional tissue oxygenation in each angiosome during endovascular therapy (EVT) of the superficial femoral artery (SFA). Materials and Methods: We devised a novel near-infrared spectroscopy oximeter, "TOE-20," for real-time monitoring of regional tissue oxygen saturation (rSO2). Using TOE-20, we prospectively assessed rSO2 at each angiosome in 23 CLTI patients who underwent successful revascularization of the SFA. During EVT, three sensor probes were placed at the dorsal foot, plantar foot, and outer ankle for rSO2 monitoring. Results: At the end of EVT, rSO2 at all angiosomes was significantly elevated by SFA revascularization. The change in rSO2 in each angiosome was larger in patients with patent relevant arteries than in those with occluded relevant arteries (i.e., anterior tibial artery patency, posterior tibial artery patency, and peroneal artery patency). Conclusion: The patency of the tibial/peroneal arteries is important for regional tissue oxygenation in EVT. Using TOE-20 and rSO2-based revascularization, it may possible to anticipate whether an ischemic ulcer will heal or not.

Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema.

Background: Secondary lymphedema (LE) occurs due to the disruption of lymphatic circulation. Lymphatic fluid accumulation in subcutaneous tissues induces adipocyte proliferation. Obesity is an important risk factor for the occurrence and deterioration of LE. Although the relationship between LE and subcutaneous adipose tissue increase has been reported clinically, their pathophysiological relationship remains unknown. Thus, we aimed to verify whether subcutaneous adipose tissue increase is involved in the pathophysiology of secondary LE. Methods and Results: The hindlimb model of secondary LE was created using male Sprague-Dawley rats (control and LE groups; n = 5 each). Skin samples were obtained on postoperative day 168. Histological examination and quantitative real-time polymerase chain reaction analysis of inflammatory adipokines, tumor necrosis factor-alpha (Tnf-α), C-C chemokine ligand 2 (Ccl2), and interleukin-6 (Il-6) were performed. Limb volume and subcutaneous adipose tissues significantly increased in the LE group compared with those in the control. Macrophages aggregated in the augmented adipose tissues, around the adipocytes, and formed crown-like structures (CLSs). The number of CLSs significantly increased in the LE group. These macrophages expressed transforming growth factor-beta 1 (TGF-ß1). Inflammatory adipokine secretion was not observed. Although Il-6 expression increased in the LE group, IL-6 was expressed in subcutaneous myofibroblasts but not in subcutaneous adipocytes. Conclusion: As TGF-ß1 derived from subcutaneous myofibroblasts is involved in skin fibrosis during LE, TGF-ß1 derived from adipose tissues may also play a similar role. Drug treatment for subcutaneous adipose tissue reduction may improve the skin condition in secondary LE and may be a new therapeutic strategy.

Real-time assessment of tissue oxygen saturation during endovascular therapy for chronic limb threatening ischemia using a novel oximeter.

In the present study, we have introduced a novel real-time, near-infrared spectroscopy oximeter, the TOE-20 (Astem, Co, Ltd, Kawasaki, Japan), which can simultaneously measure the regional tissue oxygen saturation (rSO2) in the skin and subcutaneous tissue at three angiosomes of the foot. Seven patients with chronic limb threatening ischemia who had undergone successful revascularization of the superficial femoral artery were included. The analysis revealed a significant correlation between the rSO2 and skin perfusion pressure. After revascularization, the rSO2 and skin perfusion pressure had both increased at the three regions, although the increase at the plantar foot was insignificant. These results indicate that the TOE-20 can be successfully used to monitor the rSO2 during endovascular treatment.

A Pilot Study Investigating the Use of Regional Oxygen Saturation as a Predictor of Ischemic Wound Healing Outcome after Endovascular Treatment in Patients with Chronic Limb-Threatening Ischemia.

Objective: To determine the prognostic value of regional tissue oxygenation saturation (rSO2) for ulcer healing after endovascular treatment (EVT) of peripheral arterial disease (PAD). Materials and Methods: Among PAD patients, 34 patients with chronic limb-threatening ischemia underwent EVT for limb salvage. We retrospectively analyzed the cutoff rSO2 values on postoperative day 1 to predict ulcer healing and patient prognosis. Skin perfusion pressure (SPP) and transcutaneous oxygen pressure (TcPO2) were also used to assess wound healing. Results: A finger-mounted tissue oximeter can easily measure rSO2 on the dorsal foot. Among the 34 patients, the ulcer healed in 25, and no changes were observed in 2 patients at 1 month after EVT. However, 7 patients needed major amputation at the same time. Wound healing was achieved in all patients with rSO2≥50%. With this cutoff, the sensitivity and specificity of the new device for wound healing were 100% and 64%, respectively. In all the wound healing cases, SPP was ≥45 mmHg, and TcPO2 was ≥40 mmHg. Conclusion: To assess limb ischemia, rSO2 can be measured quickly and easily using this device. We suggest that an rSO2>50% shows good prognosis for ulcer healing.

Target region oxygenation-based endovascular treatment in a chronic limb-threatening ischemia patient with multifocal arterial diseases.

Patients with chronic limb-threatening ischemia often have multiple segmental diseases requiring revascularization. However, there is no defined milestone to indicate sufficient endovascular treatment (EVT). Using multiple near-infrared spectroscopic oximeters, we intraoperatively monitored regional tissue oxygen saturation (rSO2) to perform target region oxygenation-based EVT for a patient with chronic limb-threatening ischemia. Stent placement at the superficial femoral artery and angioplasty of the tibioperoneal trunk enabled rSO2 in the target ischemic regions (dorsal foot and heel) to be >50% for ulcer healing. We herein describe target region oxygenation-based EVT with rSO2 monitoring as an effective strategy for performing the minimum requisite procedures.

K-134, a phosphodiesterase 3 inhibitor, reduces vascular inflammation and hypoxia, and prevents rupture of experimental abdominal aortic aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease, which frequently results in fatal rupture; however, no pharmacologic treatment exists to inhibit AAA growth and prevent rupture. In this study, we investigated whether K-134, a novel phosphodiesterase 3 inhibitor, could limit the progression and rupture of AAA using multiple experimental models. METHODS: A hypoperfusion-induced AAA rat model was developed by inserting of a small catheter and via tight ligation of the infrarenal aorta. Rats were fed with a 0.15% K-134-containing diet (K-134(+) group) or a normal diet (K-134(-) group) from 7 days before the experiment to 28 days after model creation (pretreatment protocol). After the administration period, elastin fragmentation, macrophage infiltration, reactive oxygen species expression, matrix metalloproteinase levels, aneurysmal tissue hypoxia, and adventitial vasa vasorum (VV) stenosis were assessed. In the delayed treatment protocol, rats with AAA >3 mm were randomly divided to K-134(+) or K-134(-) group 7 days after model creation, and the effect of K-134 on suppressing preexisting AAA was examined. Further, elastase-induced rat model and angiotensin II-infused ApoE-/- mouse model were also used to examine the ability of K-134 to prevent rupture. RESULTS: K-134 prevented AAA rupture and significantly improved survival in the pretreatment protocol (P < .01). In the K-134(+) group, elastin degeneration was prevented; macrophage infiltration and reactive oxygen species production were significantly decreased. At 14 days, the enzymatic activity of matrix metalloproteinase-9 was significantly decreased. Further, K-134 inhibited intimal hyperplasia and VV stenosis. Expressions of hypoxic markers, hypoxia-inducible factor-1α, and pimonidazole, in the aneurysmal wall were also attenuated. In the delayed treatment protocol, K-134 also improved survival of rats with preexisting AAA. Similarly, in the elastase-induced rat model and angiotensin II-infused ApoE-/- mouse model, K-134 inhibited rupture and significantly improved survival (P < .01). CONCLUSIONS: K-134 prevented the rupture of AAA and improved survival through suppressing inflammatory reaction. The inhibition of intimal hyperplasia in the adventitial VV may be associated with reduced hypoxia in the aneurysmal tissue. (JVS-Vascular Science 2020;1:219-32.). CLINICAL RELEVANCE: This study shows that K-134, a novel phosphodiesterase 3 inhibitor, suppressed abdominal aortic aneurysm (AAA) rupture. Considering that K-134 had already undergone a phase Ⅱ study in the United States for claudication in peripheral artery occlusive disease patients with good tolerance, K-134 may become a promising new therapeutic option for AAAs and could undergo clinical trials for patients with small AAA.

Development of a Noninvasive Skin Evaluation Method for Lower Limb Lymphedema.

Background: The skin's condition is altered in lymphedema patients, and evaluating this change is important. Some noninvasive methods for evaluating skin condition have been reported, especially in upper limb lymphedema. However, evaluating the skin in lower limb lymphedema remains challenging and is often limited to palpation. We aimed to develop a noninvasive skin evaluation method for lower limb lymphedema patients. Methods and Results: Twenty-five lower limb lymphedema patients were included. Skin induration and elasticity were measured using Indentometer® IDM 400 and Cutometer® MPA580. The relationship between the properties of skin from the healthy forearm and thigh, those of the affected thigh, and age was analyzed. Predicted skin induration age (IA) and elasticity age (EA) were calculated from the forearm, whereas actual values were calculated from the thigh, and the differences (ΔIA and ΔEA) were assessed. Patients were classified according to the International Society of Lymphology clinical staging system, and the differences in ΔIA and ΔEA were analyzed among the three groups (healthy, stage I/IIa, and stage IIb/III). Skin biopsy was performed in five unilateral lower limb lymphedema patients, and the dermal elastic fiber area was determined using microscopy with Elastica van Gieson staining. ΔEA significantly increased with disease progression, but ΔIA did not change significantly. Microscopy revealed elastic fiber filamentous changes, with decreased elastic fiber areas in lymphedema-affected skin. Conclusion: To our knowledge, this is the first report to evaluate lower limb skin elasticity in lymphedema quantitatively and noninvasively. ΔEA is useful for evaluating skin condition progression in lymphedema patients.

Utility of a Finger-Mounted Tissue Oximeter with Near-Infrared Spectroscopy to Evaluate Limb Ischemia in Patients with Peripheral Arterial Disease.

Objective: To investigate whether a finger-mounted tissue oximeter is useful in evaluating limb blood flow in patients with peripheral arterial disease (PAD). Materials and Methods: Seventy-two patients with PAD were included, and the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and skin perfusion pressure (SPP) were measured. The regional tissue oxygenation saturation (rSO2) was measured using a finger-mounted tissue oximeter at the ankle, dorsal foot, and each dorsal and plantar toe. Correlations between rSO2 and ABI and between TcPO2 and SPP were analyzed. The patients were divided into three groups: Fontaine IIa (F-IIa), IIb (F-IIb), and III and IV (F-III/IV) groups. The difference in rSO2 between each group was analyzed. Results: Significant correlations were observed between rSO2 and TcPO2 and between rSO2 and SPP. TcPO2 and SPP in the F-III/IV group were significantly lower than those in the F-IIa group. rSO2 in the F-IIb and F-III/IV groups was significantly lower than that in the F-IIa group. Conclusion: The measurement of rSO2 using finger-mounted tissue oximetry is quick, simple, and painless. It can be used on any skin area and is useful to evaluate limb circulation in patients with PAD.