• Toxicological Research
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• 제30권3호
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• pp.141-148
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• 2014

Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin ($PGI_2$), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.287-298
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• 2020

Ca²⁺ signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca²⁺ signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca²⁺ concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K⁺ efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca²⁺ influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca²⁺-permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca²⁺-sensitive K⁺ channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca²⁺ signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca²⁺ dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.

• 생명과학회지
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• 제32권2호
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• pp.175-188
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• 2022

혈관과 섬유증 기관들의 평활근과 세포외기질에 대한 릴랙신의 조절기능이 입증되어왔다. 본 총설에서는 저항성 소동맥과 방광을 포함한 섬유증 기관들의 세포외기질에 작용하는 릴랙신의 다양한 기전들을 고찰한다. 릴랙신은 혈관 평활근육의 수축을 억제하고, 콜라겐과 같은 세포외기질의 구성성분들을 감소키켜 혈관벽의 수동적 신전성을 증가시킴으로써, 혈관확장을 유도한다. 릴랙신이 동맥의 혈관확장을 유도하는 주된 세포기전은 RXFP1/PI3K의 활성화, Akt 인산화 및 eNOS 활성화를 통한 내피세포-의존성 산화질소의 생성에 의해 매개된다. 추가적으로, 릴랙신은 또한 다른 대체경로들을 작동하여 신장과 장간막 동맥의 혈관확장을 증가시킨다. 신장 소동맥에서, 릴랙신은 내피세포의 MMPs 및 EtB 수용체의 활성화와 VEGF 및 PlGF의 생성을 촉진하여, 평활근의 수축성과 콜라겐의 침착을 억제함으로써 혈관확장을 초래한다. 이와 달리, 장간막 소동맥에서, 릴랙신은 bradykinin (BK)-유도 이완을 시간-의존적으로 증강시킨다. BK-매개 이완의 신속 증가는 IK_Ca 이온통로와 뒤이은 EDH 유발에 의존하는 반면, BK에 의한 지속적 이완은 COX 활성과 PGI₂에 의존한다. 릴랙신의 항섬유화 효과는 염증유발 면역세포의 침투, endothelial-to-mesenchymal transition (EndMT) 및 근섬유아세포의 분화와 활성을 억제하여 매개된다. 릴랙신은 또한 근섬유아세포 내 NOS/NO/cGMP/PKG-1 경로를 활성화하여, TGF-β1-유도 ERK1/2 및 Smad2/3 신호의 활성과 ECM 콜라겐의 침착을 억제한다.

• Journal of Chest Surgery
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• 제14권1호
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• pp.9-16
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• 1981

Twenty eight patients with conpnital heart disuse underwent lung biopsy to assets pulmonary obstructive vascular disease at cardiac surpry. Thirteen patients had patent ductus arteriosus, 10, ventricular septal defects and S, atrial septal defects. The aaes were between 2 and 30 years. In patients with patent ductus arteriosus lung biopsy was performed from the IIngular Hlment. The anterior seament of the right upper lobe was blopsled in cases with ventricular septal defect and atrial septal defect. Grading of pulmonary obstructive vascular disease could not be assessed In 9 cases. In 2 cases poor quality of the slides made us impossible to evaluate and In 7 cases there were no suitable small muscular arteries to evaluate in the slides of lung tissue especially taken from the IIngular seament. Nineteen cases were evaluated pulmonary obstructive vascular disease. Among them 17 cases had Heath-Edwards changes of grade 1 and 2 patients had that of grade 3. The thickness of media was measured. It was expressed as percentage of medial thickness to outer diameter of artery. The medial thickness was correlated proportionally with elevation of pulmonary arterial pressure and pulmonary vascular resistance to systemic vascular resistance ratio. There were no complications related to the procedure of lung biopsy.

• Journal of Chest Surgery
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• 제16권1호
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• pp.18-29
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• 1983

Thirty-two patients with a cyanotic cardiac malformations having more complex intracardiac defects than ones in a tetralogy of Fallot underwent complete intracardiac repairs in a-full-year period from July 1981 to June 1982. Twenty-two patients [68.8%] died within 30 days after surgery: Transposition of the great arteries, seven of 10 patients; Double-outlet right ventricle, four of 6 patients; Tricuspid atresia, four of 6 patients; Single ventricle, all of 4 patients; Pulmonary atresia, two of 3 patients; Double-outlet left ventricle, none of 2 patients; and Truncus arteriosus, one of a single patient. All deaths occurred with a low cardiac output syndrome or a failed off-bypass, and they were almost always accompanied with other grave postoperative complications. The complex intracardiac anatomy itself was one of the risk factors by making a complete intracardiac repair of the defects difficult in a small heart. The reconstruction of the right ventricular outflow carried a difficulty in balancing an adequate relief of the obstruction with an avoidance of making too much pulmonary valvular insufficiency as well. On the other hand, the presence of an elevated pulmonary arterial pressure and a high pulmonary vascular resistance was also the factors affecting the postoperative surviv als. The importance of detailed knowledge of intracardiac anatomy and hemodynamics from the careful preoperative evaluation of the patient was discussed along with the necessity of technical refinement of the correction.

• 대한임상검사과학회지
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• 제36권1호
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• pp.43-48
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• 2004

Cerebral vasoreactivity is an index of autoregulation of cerebral perfusion, and can be measured using functional images such as Xe CT, SPECT and PET in reponse to hypercapneic stimulus. In order to measure cerebral $CO_2$ vasoreactivity in routine TCD study conveniently and reliably, we devised a method of rebreathing into closed volume of reservoir bag as a hypercapneic stimulus, and applied it to 44 healthy volunteers. As a hypercapneic stimulus, we applied fitting mask connected with closed reservoir bag for about 90 seconds, and mean blood flow velocity(MBFV) and pulsatility index(PI) were evaluated at proximal middle cerebral arteries(MCA) of 50-55 mm depth, before and after the hypercapneic stimulus. Age affected the MFV and PI value showed significant and the MFV was 56.45(SD=9.75)cm/sec, while PI was 0.406(SD=0.089). As age increases the flow velocity decreased significantly whereas PI value increased(P<0.05). The vasoreactvity significantly decreased with age(P<0.05). The decrease of cerebral blood flow quantity and cerebral blood flow velocity is not only because of increase of diameter of cerebrovascular resulting from aging, but the resistance increase of small blood vessel resulting from the increase of PI & RI value is regarded. We suppose that the rebreathing method is a reliable and convenient technique as a hypercapneic stimulus in determining cerebral $CO_2$ vasoreactivity. The rebreathing method could be non-invasive and useful methods in estimation of the cerebrovascular reactivity and could be applied to the basal and follow-up evaluation of the cerebrovascular reserve of the ischemic stroke patients.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권5호
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• pp.375-384
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• 2011

Purpose: The advent of microsurgical technique and instruments, particularly in the field of perforator flap and supermicrosurgery, which have expanded the scope of microsurgery. However, supermicroanastomosis without any compression, tension, or distortions must be achieved to reach successful outcomes. Small-caliber vessels, such as those with an internal diameter less than 0.2 mm, are susceptible to inadvertent twisting of the anastomosis. In this study, using the superficial inferior epigastric artery (SIEA)-based flap model in Sprague-Dawley (SD) rats, we evaluated the acceptable limits of twisting effects on supermicroanastomotic sites. Methods: A total of 20 supermicroanastomoses were performed using the SIEA-based flap model in 10 male SD rats, 10-weeks-of-age, weighing 300~350 g. Rats were divided into five groups of two with four flaps as follows: 1) sham, 2) control group with end to end SIEA arterial supermicroanastomosis, 3) experimental I (EA1) with $90^{\circ}$ twisting, 4) experimental II (EA2) with $180^{\circ}$ twisting, and 5) experimental III (EA3) with $270^{\circ}$ twisting of the supermicroanastomosis. Each SIEA was anastomosed using six 11-0 $Ethilon^{(R)}$ (Ethicon Inc. Co., NJ, USA) stitches except in the sham group where the SIEA was only clamped with Supermicro vascular $clamps^{(R)}$ (S&T, Neuhausen, Switzerland) for 20 minutes. Results: The anastomosed arterial patency showed no remarkable changes according to doppler waveforms measured with a Smardop 45 Doppler System (Hadeco Inc., Kawasaki, Japan). The pulsatility index (PI) was increased at postoperative day 10 in the EA2 and EA3 groups, and the resistance index (RI) showed no statistically significant difference between preoperative and postoperative values at 10 days. Histologic specimens from the EA3 group showed increased tunica media necrosis, convolution of the internal elastic lamina, densely packed platelets, fibrin, and erythrocytes. Flap viability and anastomosed vessel patency were not significantly affected by the degree of arterial twisting in this study, other than in the EA3 group where minor effects on arterial patency of the microanastomoses were encountered. Conclusion: It appears that minor twisting on small caliber arteries, used in supermicroanastomoses, can be tolerated. However, twisting should be avoided as much as possible, and more than $180^{\circ}$ twisting must be prevented in clinical practice.

• 대한한방내과학회지
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• 제22권2호
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• pp.199-205
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• 2001

Background and Purpose : Transcranial doppler ultrasonography(TCD) is a noninvasive and nonradioactive technique for evaluation of the hemodynamics in large cerebral vessels. Sahyangsohap-won(SS) has been considered to be effective for the treatment of various disease, especially cerebrovascular, cardiovascular, and psychosomatoform disorders. But, there is no study about the effect of SS on the cerebral hemodynamics in humans. The aim of this study was to assess the effect of SS on the changes in cerebral hemodynamics and the dose-dependant effect by using TCD. Subjects and Methods : 30 healthy subjects were randomly divided into three group: group 1 took no drug, group 2 took SS one pill, and group 3 took SS 2 pills. Changes in the mean blood flow velocity(MBFV) and pulsatility index(PI) in the middle cerebral artery were evaluated by means of TCD. We obtained hypercapnia with breath-holding and evaluated cerebrovascular reactivity with the breath-holding index(BHI). Systolic blood pressure(SBP), diastolic blood pressure(DBP), and heart rate(HR) were measured by means of ambulatory blood pressure monitoring. In group 2 and group 3, the evaluations were performed during the baseline and were repeated at 20, 40, and 60 minutes after SS administration. In group 1, the evaluation was performed at corresponding time intervals. Results : In mean values of MSFV, PI, SSP, DBP, and HR, no stastically significant differences were found between the 3 groups. However, BHI values were significantly lower in groups 2 and 3 than in group 1 at 40 minutes after SS administration(P<0.05, group 1 vs group 2, group 1 vs group 3 by post-hoc analysis: Scheffe's test) but in dose-dependant effect, there was no difference between group 2 and group 3. Conclusion : These results suggest that SS can decrease vascular resistance in cerebral small arteries or arterioles and enhance their distensibility. Further studies on larger numbers of subjects are needed to confirm these effects and the dose-dependant effects.