Abstracts from the 47th Annual Meeting of Japanese Society for Microcirculation

Abstract

We aneurysms based the in vascular endothelial cells triggers aneurysm development. Methods : We investigated the role of P2X4 purinoceptor, which is involved in flow- sensitive mechanisms in vascular endothelial cells, in the development of cerebral aneurysms by using the aneurysm-induced animal model. We also prospectively enrolled human patients with unruptured cerebral aneurysms, observed them for 3 years with cerebrovascular 3D imaging and carotid artery echo -cardiography, and compared the hemodynamic environments of the growth group with those of the non- growth group using computa-tional fluid dynamics (CFD) technique. Results : The incidence of cerebral aneurysms in aneurysm- induced P2X4 (−/−) mice was significantly lower than that in P2X4 (+/+) mice, and the incidence of cerebral aneurysms in aneurysm- induced rats treated with a P2X4 inhibitor, paroxetine was significantly lower than that in the non- treated group. Paroxetine treatment also significantly suppressed aneurysm growth. In the clinical study of human unruptured cerebral aneurysms, 461 patients were enrolled, and during the 3- year observation period, 38 aneurysms enlarged and 209 ones did not. In the CFD analysis, the magnitude of wall shear stress and transWSS, a metrics for shear stress disturbance, was significantly increased in the enlarged group, especially in the aneurysm neck. Normal brain function depends on stable cerebral blood flow and cerebral autoregulation. Cerebral blood flow is maintained even when blood pressure fluctuates. However, microcirculation in the cortex is not well understood when blood pressure drops rapidly. The purpose of this study was to determine oxyhemoglobin (O 2 Hb) changes, the indicator of cortical blood flow changes, during hypotension induced by thigh cuff release. Ten healthy students participated in this study. They were seated in a recumbent position in a quiet room. The cuffs of digital tourniquets were placed on both thighs and inflated to 250 mmHg for 5 min after 5 min rest, followed by deflation for 5 min. Right (R- ) and left (L- ) prefrontal cortex (PFC) O 2 Hb levels were measured using a multi- channel near- infrared spectroscopy system (LABNIRS; Shimadzu Co). O 2 Hb levels for each area were measured. Beat- to- beat mean arterial pressure (MAP) was recorded by volume clamping the finger pulse with a finger photoplethysmograph (Finometer; Finapres Medical Systems) on the left middle finger. O 2 Hb and MAP were averaged 1- sec epoch throughout the experi-ment. This study was approved by the Ethics Committee of Niigata University of Health and Welfare (18649- 210618). The decrease in MAP after the cuff release was 31.3 ± 5.6 mmHg. The decrease in O 2 Hb levels in the L- PFC (0.196 ± 0.088 mM∙cm) was larger than that in R- PFC (0.165 ± 0.072 mM∙cm) ( p < .05). These results suggest that the effect of hypotension induced by thigh cuff release on cortical blood flow might be different between cortical regions. Background : Persistently high serum levels of triglyceride (TG) and free fatty acid (FFA), which are commonly observed in metabolic syndrome and type 2 diabetes mellitus, are residual risk factors after statin therapy for atherosclerotic cardiovascular disease (ASCVD). The elevation of plasma FFA levels after lipid/heparin infusion results in endothelial and microvascular dysfunction in healthy subjects. However, the effects of lowering serum TG and FFA on microcirculation are unclear. Pemafibrate, an orally active, a novel selective peroxisome proliferator- activated receptor α modulator (SPPARMα), is used for treatment of hypertriglyceridemia in clinical setting. The aim of this study is to explore the effects of pemafibrate on hemorheology, leukocyte activation, and plasma levels of FFA. Method : The study design was a single- center, prospective, obser-vational study with propensity score analysis. Study patients were aged 20 years or older, type 2 diabetes mellitus (HbA1c 6%– 10%) and/or metabolic syndrome associated with fasting TG ≥150 mg/dl within 2 weeks, and whole blood transit time (corrected) >45 s on microarray channel flow analyzer (MCFAN). Finally, 50 patients who were newly prescribed pemafibrate 0.2 mg/day p.o., and HIIE a order. The HIIE of high- intensity at 80% VO for 3- min and low- intensity exercise at 40% VO for 3- min repeated times. The consisted of moderate intensity exercise at 60% VO for 24- min. Oxygenated hemoglobin (O 2 Hb) levels were measured at right (R- ) and left (L- ) prefrontal cortex (PFC), premotor cortex (PMC), supplementary motor area (SMA), and primary motor cortex (M1) using a multi- channel near- infrared spectroscopy Co). The oxygenated hemoglobin (O 2 Hb) levels during exercise were integrated and compared between HIIT and MICE. The 2 Hb of HIIE 14.6 mM∙cm∙sec) higher than MICE ± 8.8 mM∙cm∙sec) in the M1 p < .05). In contrast, there were no significant intergroup differences in O 2 Hb in the L-PFC (40.1 ± 13.2 vs. 42.6 ± 9.5 mM∙cm∙sec), R- PFC (35.3 ± 12.6 vs. 46.9 ± 8.8 mM∙cm∙sec), L- PMC (33.9 ± 6.4 vs. 31.0 ± 7.1 mM∙cm∙sec), R- PMC (32.9 ± 9.0 vs. 38.6 ± 10.0 mM∙cm∙sec), or SMA (40.6 ± 10.9 vs. 25.6 ± 9.8 mM∙cm∙sec). suggested that HIIE induces greater cortical oxygenation in the M1 than MICE did even though the same workload. Diabetes impairs microvascular function and induces morphologi-cal changes in skeletal muscle microvasculature. Transcapillary O 2 gradients are necessary to drive blood- myocytes. We tested our hypothesis that the diabetes reduces skeletal muscle PO 2 gradients (PO 2mv – PO 2is , microvascular and interstitial PO 2 , respectively) from rest to contractions. Adult male Wistar rats ( n = 12, 6– 8 weeks old, 224.8 ± 40.0 g) were divided into diabetic (DIA: streptozotocin i.p.) and sham (saline i.p.) groups. Eight weeks later, the pO 2mv and PO 2is of the extensor digitorum longus (EDL) muscle were measured at rest and during muscle contraction using the phosphorescence quenching method. Muscle contraction was elicited by electrical stimulation (1 Hz, 6 V, 180 s). As compared to sham group, resting PO 2mv and the amplitude of the decrease in PO 2mv with contraction was higher in DIA ( p < .05, respectively). From rest to muscle contractions, there was no significant difference in PO 2is between DIA and sham groups. The pressure gradient between PO 2mv and PO 2is at rest was higher in the DIA compared to the sham. These results suggested that driving force for oxygen transfer was higher from rest to muscle contractions in diabetic rats compared to sham rats. The high driving force for oxygen transfer may be a compensatory effect of the morpho-logical or functional changes in skeletal muscle microvasculature associated with diabetes. Y- 07: Perivascular flow dynamics revealed with two- photon Background : Perivascular flow in the brain, also known as glym-phatic system, may function as a washout mechanism of large molecules, including amyloid beta in Alzheimer’s disease. Flow dynamics of perivascular space was evaluated with live imaging system using two- photon microscopy. Transportation of Background : Multiorgan failure in sepsis induces microcirculatory disturbances in the organs. In septic rat induced by cecal ligation and puncture (CLP), capillary blood flow was limited in skeletal muscle, which may impair oxygen delivery- to- utilization matching. However, skeletal muscle oxygen delivery- to- utilization matching from rest to contractions is unknown. The aim of this study is to test the hypothesis that interstitial PO 2 (PO 2is ) is limited from rest to contraction in septic model rats. Method : Male Sprague- Dawley rats ( n = 16, 2– 3 months old) were randomly divided into CLP and SHAM groups. The left spinotrapezius muscle PO 2is was measured via phosphorescence quenching during muscle contractions induced by electrical stimulation (1 Hz, 2 ms, 6 V for 180 s). Results : No group difference were found for the resting PO 2is (CLP 13.0 ± 1.9 vs. SHAM 14.9 ± 2.5 mmHg, p > .05). However, the nadir PO 2is during the muscle contractions was lower in CLP than SHAM (CLP 2.0 ± 1.1 vs. SHAM 5.7 ± 3.6 mmHg, p < .05). In the CLP, the time constant of oxygen dynamics at the onset of contraction was faster compared with SHAM (CLP 6.1 ± 1.7 vs. SHAM 10.6 ± 5.1 s, p < .05). Conclusion : In the rat model of sepsis, the spinotrapezius PO 2is during muscle contractions was lower, and the response was faster to These results may reflect a sepsis- induced mis-match