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Korean J Crit Care Med > Volume 17(2); 2002 > Article
Korean Journal of Critical Care Medicine 2002;17(2): 107-118.
원저 : Naloxone이 심근 수축에 미치는 영향; 기계적 및 전기생리학적 연구
김기준, 이행철, 이기영, 김지영, 주승택, 박윤곤
연세대학교 의과대학 마취통증의학교실
The Direct Myocardial Depressant Effect of Naloxone in Vitro: Mechanical and Electrophysiological Actions
Ki Jun Kim, Haeng Cheol Lee, Ki Young Lee, Ji Young Kim, Sueng Teck Joo, Wyun Kon Park
Department of Anesthesiology, Yonsei University, College of Medicine, Seoul, Korea. wkp7ark@yumc.yonsei.ac.kr
ABSTRACT
BACKGROUND: Naloxone,an opioidant agonist, has been s hown t o have a c ar di ovascular pressor effect in states of hemorrhagic and endotoxic shock.We determined the direct inotropic effect of naloxone using guinea pig right ventricular papillary muscles. METHODS: With institutional approval,isometric contractile force was measured in normal and 26mM K+ Tyrode's solution at various stimulation rates.Normal and slow action potentials (APs) were measured with conventional microelectrode technique.The effects of naloxone on sarcoplasmic recticulum function were evaluated by measuring rapid cooling contractures (RCCs)in normal Tyrode 's solution and rested-state (RS)contraction in low Na+ (25 mM)Tyrode's solution.Patch clamp study was performed to examine the direct effect on Ca2+ current in myocytes. RESULTS: Naloxone (50,100,200 micro M)caused dose-dependent depression of peak force and maximal rate of peak force (dF/dt-max)by 30,50 and 70%,respectively.Modest depression was shown in RS contraction in low Na+ Tyrode's solution.In 26 mM K+ Tyrode's solution,100 micro M naloxone markedly depressed late force development.100 micro M naloxone depressed RCCs by 20%. While 100 micro M naloxone did not alter amplitude or dV/dt-max in normal and slow APs at 0.25 Hz, AP duration was prolonged significantly.In patch clamp study,50 micro M naloxone depressed Ca2+ current by 50%. CONCLUSIONS: Naloxone depresses contractile force.Myocardial depressant effect partly seems to be caused by depressed Ca2+ influx through cardiac membrane.Rapid release of Ca2+ from the sarcoplasmic reticulum by depolarization and release by rapid cooling seems to be minimally affected.
Key Words: Heart; Calcium current; Myocardial contraction; Myocardium; Naloxone
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