Stimulation of kappa(2)- and sigma-receptors as a possible approach to prevention of myocardial dysfunction caused by reperfusion

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.