Effects of a selective inhibitor of Na+/Ca2+ exchange, KB-R7943, on reoxygenation-induced injuries in guinea pig papillary muscles

J Cardiovasc Pharmacol. 2000 Jan;35(1):121-8. doi: 10.1097/00005344-200001000-00016.

Abstract

The effects of a novel agent that is reported to selectively block Ca2+ influx by Na+/Ca2+ exchange (NCX), KB-R7943, on the reoxygenation-induced arrhythmias and the recovery of developed tension after reoxygenation, were investigated in guinea pig papillary muscles. KB-R7943 dose-dependently suppressed the contracture tension during low-sodium (21.9 mM) perfusion (23+/-8% of steady-state developed tension at 10 microM vs. 56+/-11% in control; n = 6, p<0.05), but did not change action potential and contractile parameters. During the reoxygenation period after 60-min substrate-free hypoxia, KB-R7943 (10 microM) significantly decreased the incidence of arrhythmias (44 vs. 100% in control; n = 9, p <0.05) and shortened the duration of arrhythmias (16+/-11 vs. 72+/-14 s; p<0.01). KB-R7943 (10 microM) significantly enhanced the recovery of developed tension after reoxygenation (83+/-4 vs. 69+/-3% in control; p<0.05). We conclude that KB-R7943 (10 microM) selectively inhibits the reverse mode of NCX, and that it attenuates reoxygenation-induced arrhythmic activity and prevents contractile dysfunction in guinea pig papillary muscles. These results suggest that Ca2+ influx by NCX may play a key role in reoxygenation injury.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Arrhythmias, Cardiac / physiopathology
  • Calcium / metabolism
  • Electrophysiology
  • Guinea Pigs
  • Heart / drug effects*
  • Hypoxia / physiopathology
  • In Vitro Techniques
  • Male
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism*
  • Oxygen Consumption / drug effects*
  • Papillary Muscles / metabolism
  • Sodium-Calcium Exchanger / antagonists & inhibitors*
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology

Substances

  • 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
  • Sodium-Calcium Exchanger
  • Thiourea
  • Calcium