Direct myocardial depressant effect of naloxone: mechanical and electrophysiological actions in vitro
Naloxone, an opioid antagonist, has a cardiovascular pressor effect and has been used in various types of shock states. The aim was to determine the non-opioid effect on direct cardiac muscle contractility and explore the mechanism using guinea pig right ventricular papillary muscles. Methods:
With institutional approval, isometric contractile force was measured in modified normal and 26 mM K+ Tyrode solution at various stimulation rates. The effects of naloxone on sarcoplasmic recticulum function were evaluated by measuring rested-state contraction in low Na+ (25 mM) Tyrode solution and rapid cooling contracture in modified normal Tyrode solution. Normal and slow action potentials (APs) were measured using conventional microelectrode technique. Patch clamp study was performed to examine the direct effect on Ca2+ current in cardiac ventricular myocytes. Results:
Naloxone (50, 100, and 200 µM) caused a concentration-dependent depression of peak force and maximal rate of force development. Modest depression, approximately 20%, was shown in rested-state contraction in low Na+ Tyrode solution. Naloxone (100 µM) modestly depressed the rapid cooling contracture to 80 ± 3% of baseline, accompanied by prolongation of time to peak contracture by approximately 37%. In 26 mM K+ Tyrode solution, naloxone (100 µM) markedly and selectively depressed the late force development. While naloxone (100 µM) did not alter the amplitude and dV/dt-max in normal and slow APs at 0.25 Hz, AP duration was prolonged significantly. In patch clamp experiment, naloxone (50 µM) depressed Ca2+ current by approximately 50%. Conclusions:
The direct myocardial depressant effect of naloxone appeared to be in part caused by depression of Ca2+ influx through cardiac membrane. Sarcoplasmic reticulum function appeared to be modestly depressed.
Document Type: Research Article
Affiliations: 1: Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, and 2: Cardiology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea
Publication date: 01 January 2004