The Direct Myocardial Depressant Effect of Naloxone in Vitro: Mechanical and Electrophysiological Actions.
- Author:
Ki Jun KIM
1
;
Haeng Cheol LEE
;
Ki Young LEE
;
Ji Young KIM
;
Sueng Teck JOO
;
Wyun Kon PARK
Author Information
1. Department of Anesthesiology, Yonsei University, College of Medicine, Seoul, Korea. wkp7ark@yumc.yonsei.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Heart;
Calcium current;
Myocardial contraction;
Myocardium;
Naloxone
- MeSH:
Action Potentials;
Animals;
Contracture;
Depression;
Guinea Pigs;
Heart;
Microelectrodes;
Muscle Cells;
Myocardial Contraction;
Myocardium;
Naloxone*;
Papillary Muscles;
Sarcoplasmic Reticulum
- From:The Korean Journal of Critical Care Medicine
2002;17(2):107-118
- CountryRepublic of Korea
- Language:Korean
-
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.
