Lipid emulsion-mediated reversal of toxic-dose aminoamide local anesthetic-induced vasodilation in isolated rat aorta

옥성호,Jeong Yeol Han,Soo Hee Lee,신일우,이헌근,정영균,Mun-Jeoung Choi,손주태 대한마취통증의학회 2013 Korean Journal of Anesthesiology Vol.64 No.4

Background: Intravenous lipid emulsion has been used to treat systemic toxicity of local anesthetics. The goals of this in vitro study were to determine the ability of two lipid emulsions (IntralipidⓇ and LipofundinⓇ MCT/LCT) to reverse toxic dose local anesthetic-induced vasodilation in isolated rat aortas. Methods: Isolated endothelium-denuded aortas were suspended for isometric tension recording. Vasodilation was induced by bupivacaine (3 × 10-4 M), ropivacaine (10-3 M), lidocaine (3 × 10-3 M), or mepivacaine (7 × 10-3 M) after precontraction with 60 mM KCl. IntralipidⓇ and LipofundinⓇ MCT/LCT were then added to generate concentration-response curves. We also assessed vasoconstriction induced by 60 mM KCl, 60 mM KCl with 3 × 10-4 M bupivacaine, and 60 mM KCl with 3 × 10-4 M bupivacaine plus 1.39% lipid emulsion (IntralipidⓇ or LipofundinⓇ MCT/LCT). Results: The two lipid emulsions reversed vasodilation induced by bupivacaine, ropivacaine, and lidocaine but had no effect on vasodilation induced by mepivacaine. LipofundinⓇ MCT/LCT was more effective than IntralipidⓇ in reversing bupivacaine-induced vasodilation. The magnitude of lipid emulsion-mediated reversal of vasodilation induced by high-dose local anesthetics was as follows (from highest to lowest): 3 × 10-4 M bupivacaine-induced vasodilation, 10-3 M ropivacaine-induced vasodilation, and 3 × 10-3 M lidocaine-induced vasodilation. Conclusions: LipofundinⓇ MCT/LCT-mediated reversal of bupivacaine-induced vasodilation was greater than that of IntralipidⓇ; however, the two lipid emulsions equally reversed vasodilation induced by ropivacaine and lidocaine. The magnitude of lipid emulsion-mediated reversal of vasodilation appears to be correlated with the lipid solubility of the local anesthetic.

Lipid Emulsions Enhance the Norepinephrine-Mediated Reversal of Local Anesthetic-Induced Vasodilation at Toxic Doses

이수희,성희진,옥성호,유종선,최문정,손주태 연세대학교의과대학 2013 Yonsei medical journal Vol.54 No.6

Purpose: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. Materials and Methods: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10-4 M levobupivacaine, 2×10-3 M ropivacaine, and 7×10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. Results: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10-3 M)-induced vasodilation. In addition,lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. Conclusion: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.

주침 수치 방법에 따른 種大黃이 백서의 흉부대동맥 혈관이완에 미치는 영향

김형환,이현경,강순아,안덕균,박성규 대한본초학회 2004 大韓本草學會誌 Vol.19 No.1

Objectives: We have examined the relaxative response to the water extract of Rheum undulatuum (ERU) and water extract of alcohol processed Rheum unddatum (ARU) with isolated thoracic aorta from sprague dawley (SD) rat Methods: Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to ERU and ARU were investigated in vessels precontracted with 5- hydroxytryptamine(5-HT). Results: We found that the thoracic aorta segments responded to ERU and ARU with a dose-dependent vasorelaxation. 1. The thoracic aorta segments responded to ERU and ARU with a dose-dependent vasodilation. 2. The amounts of emodin were 0.063% and 0.076% in ERU and ARU, respectable. 3. The 5-HT induced contraction at 10^(-4) were inhibited by 85.2±4.76% and 83.4*8.82% after addition of the 0.lmg/mL. water extract of ERU and ARU. 4. The 5-HT induced contraction at l0^(-3)% were inhibited by 100% after 10^(-3) emodin. Conclusion: In conclusion, vasodilation effect of the water extract of Rheum undulatum L. in rat thoracic aorta was not decreased according to the alcohol processing of Rheum undulatum L.

백과엽(白果葉) 및 자오가(刺五加) 가미사물탕(加味四物湯)이 백서(白鼠)의 흉부대동맥(胸部大動脈) 혈관이완(血管弛緩)에 미치는 영향

김형환,박수연,강순아,김홍렬,안덕균,박성규,Kim Hyung-Hwan,Park Soo-Yeon,Kang Soon-Ah,Kim Hong-Yeoul,Ahn Duk-Kyun,Park Seong-Kyu 대한한의학방제학회 2003 大韓韓醫學方劑學會誌 Vol.11 No.2

We have examined the relaxational response to the water extract of Angelica gigas $N_{AKAI}$ (AG), Gingko biloba $L_{INNE}$ (GB), Acanthopanax senticosus $H_{ARMS}.$ (AP) and Augumented-Four-Substance Decoction (AG-FSD, GB-FSD, AP-FSD) in isolated thoracic aorta from sprague dawley(SD) rat. Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to AG, GB, AP and AG-FSD, GB-FSD, AP-FSD were investigated in vessels precontracted with 5-hydroxytryptamine(5-HT) were compared in vasodilation effect. We found that the thoracic aorta segments responded to AG, GB, AP and AG-FSD, GB-FSD, AP-FSD with a dose-dependent vasodilation. The 5-hydroxytryptamine induced contraction at $10^{-4}M$ were inhibited by 26.3%, 75.8%, 87.5% and 6.9%, 22.6%, 30.8% after addition of the 0.1 g/mL water extract of AG, GB, AP and AG-FSD, GB-FSD, AP-FSD. In conclusion, AG, GB, AP and AG-FSD, GB-FSD, AP-FSD induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. AP-FSD has very potent vasodilation.

當歸의 種類에 따른 四物湯이 白鼠의 胸部大動脈 血管弛緩에 미치는 影響

김형환,이주호,이제현,안덕균,박성규 대한본초학회 2001 大韓本草學會誌 Vol.16 No.2

We have examined the relaxational reponse to the water extract of Angelica gigas Nakai (AG), A. sinensis(Oliv.) Diels (AS), A. acutiloba Kitagawa (AA), and Four-Substance Decoctions (AG-FSD, AS-FSD, AA-FSD) in isolated thoracic aorta from sprague dawley(SD) rat in the presence and absence of endothelium. Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to AG, AS, AA and AG-FSD, AS-FSD, AA-FSD were investigated in vessels precontracted with 5-hydroxytryptamine(5-HT) were compared in vasodilation effect. We found that the thoracic aorta segments responded to AG, AS, AA and AG-FSD, AS-FSD, AA-FSD with a dose-dependent vasodilation. The 5-hydroxytryptamine induced contraction at 10-4M were inhibited by 26.3%, 2.7%, 2.1% and 24.6%, 1.1%, 3.2% after addition of the 0.1 g/㎖ water extract of AG, AS, AA and AG-FSD, AS-FSD, AA-FSD. The 5-hydroxytrptamine induced contraction at 10^-4M with and without endothelium were inhibited by 24.6% and 6.9% after addition of the 0.1 g/㎖ water extract of AG-FSD. In conclusion, AG, AS, AA and AG-FSD, AS-FSD, AA-FSD-induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. AG-FSD has very potent vasodilation.

掌葉大黃이 白鼠의 胸部大動脈 血管弛緩에 미치는 影響

김형환,구본식,박수연,안덕균,최호영,박성규 대한본초학회 2002 大韓本草學會誌 Vol.17 No.2

Objectives : We have examined the relaxational response to the water extract of Rheum palmatum L. in isolated thoracic aorta from sprague dawley (SD) rat in the presence and absence of endothelium. Methods : Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to Rhizoma Rhei were investigated in vessels precontracted with 5-hydroxytryptamine. We found that the thoracic aorta segments responded to the water extract of Rheum palmatum L. (ERP) with a dose-dependent vasorelaxation. Results : We found that 1. The thoracic aorta segments responded to ERP with a dose-dependent vasodilation. 2. The 5-HT induced contraction at 10^-4M were inhibited by 85.8% after addition of the 0.1 g/mL water extract of ERP. 3. The 5-HT induced contraction at 10^-4M with and without endothelium were inhibited by 86.4% and 85.8% after addition of the 0.1g/mL ERP. 4. After pre-treatment of the thoracic aorta with 10^-4M N^G-monomethyl-L-arginine (L-NMMA), inducible nitric oxide synthase inhibitor, the vessels has not response to the contraction. Conclusion : In conclusion, ERP induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation and it has potent vasodilation.

운동과 고혈압 : 운동에 의한 산화질소 생성과 혈관확장에 대한 종설

성동준(Dong-Jun Sung),소위영(Wi-Young So),박혜미(Hye-Mi Park),차광석(Kwang-Suk Cha) 한국생활환경학회 2010 한국생활환경학회지 Vol.17 No.2

Hypertension is an independent risk factor for coronary artery disease and associated with endothelial dysfunction. Endothelium-derived relaxation factors (EDRF) including nitric oxide (NO) are reduced bioavailability in hypertension and cause increased agonist-induced vasoconstriction. Recently studies, regular exercise has been shown to improve endothelium function via various mechanical change as a shear stress and cell signal transduction in hypertensive animal model and in patients with hypertension. In addition, hydrogen peroxide (H₂O₂) and adiponectin independently lead to vasodilation and increasing endothelium nitric oxide synthase. H₂O₂ activates K? channel either by direct regulation of the channels or increase of endothelial nitric oxide synthease (eNOS). Hypodiponectinemia is associated with impaired endothelium-dependent vasodilation, which indicate reduced vasodilation. This review summarizes the current information on the improvement of NO bioavailability by regular exercise in hypertensive animal models and hypertensive patient.

내피세포 기능 평가에 있어서 말초맥파도달시간 측정의 의의 : 내피의존성 혈관확장반응과의 비교 연구 a Comparison with Flow-Mediated Vasodilation(FMD)

김무현,금동성,정석환,한승호,임태형,박은희,김영대,김종성,김광년,정동근,김희선 대한순환기학회 2004 Korean Circulation Journal Vol.34 No.2

혈관과 섬유증의 평활근 및 세포외기질 조절에 대한 릴랙신의 다양한 작용기전

민계식 한국생명과학회 2022 생명과학회지 Vol.32 No.2

Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IKCa channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI2. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen. 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 IKCa 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.

개심술후 발생한 Vasodilatory Shock의 치료 : Arginine Vasopressin의 소량투여요법 - 3례 보고 -

이교준,김해균,정은규,김도형,강두영,이응석 대한흉부외과학회 2002 Journal of Chest Surgery (J Chest Surg) Vol.35 No.3

=Treatment of Vasodilatory Shock after Cardiac Surgery: Low Dose Arginine Vasopressin Therapy- Three cases report - 혈관확장성 쇼크(Vasodilatory shock)는 혈관마비 증후군(vasoplegic syndrome), 심폐바이패스후 혈관마비(post-cardiopulmonary bypass vasoplegia)라고도 불리며, 개심술 직후 나타나는 저혈압, 빈맥, 정상 또는 약간 증가한 심박출량 및 체혈관저항 감소 등을 특징으로 하며, 일반적인 수액공급이나 카테콜아민 혈관수축제(cathecolamine vasopressor)에 대한 반응이 적거나 거의 없기 때문에 개심술후 높은 이환율 및 사망율을 나타내는 상태를 말한다. 저자들은 개심술후 혈관확장성 쇼크(vasodilatory shock)로 진단되는 3명의 환자들에서 저용량의 아르기닌 바소프레신(AVP)를 사용하여 성공적으로 치료하였기에 관련된 문헌 고찰과 함께 보고하는 바이다.