Yb. Lishmanov et al., Stimulation of kappa(2)- and sigma-receptors as a possible approach to prevention of myocardial dysfunction caused by reperfusion, KARDIOLOGIY, 41(1), 2001, pp. 70-76
It was found that intravenous administration of a-receptor agonists (+)-SKF
10047 and (+)-bremazocine or kappa (2)-agonist (-)-bremazocine resulted in
increased tolerance of isolated perfused rat heart to ischemic and reperfu
sion damages. Both kappa (2)- and sigma -receptor stimulation prevented the
development of reperfusion contracture, increased left ventricular develop
ed pressure, the double product, +dP/dt and -dP/dt. Only sigma -receptor ag
onists (d-SKF 10047 and d-bremazocine) prevented arrhythmias caused by reox
ygenation. By contrast, only kappa (2)-agonist (-)-bremazocine prevented de
velopment of reperfusion no-reflow phenomenon in vitro and increased tolera
nce of the heart to arrhythmogenic action of epinephrine in vivo. Of the th
ree compounds tested, only (+)-SKF 10047 abolished reoxygenation cell membr
ane injuries. Thus activation of cardiac sigma- and kappa (2)-receptors mig
ht be useful for prevention of myocardial stunning. Stimulation of sigma- a
nd kappa (2)-receptors can be used for protection of the heart against arrh
ythmogenic action of reperfusion and adrenergic agents, respectively. kappa
(2)-receptor agonists can be used for prevention of no-reflow phenomenon a
nd a-receptor agonist (+)-SKF 10047 - for protection against cardiac sarcol
emma injury.