Salutary effect of tedisamil on post-ischemic recovery rat heart: Involvement of sarcolemmal (Na,K)-ATPase

The in vitro effect of tedisamil on the specific activity and kinetic param eters of the sarcolemmal (Na,K)-ATPase as well as its ex vivo effect on the (Na,K)-ATPase in the isolated, perfused rat hearts was determined. Five mu mol/l of tedisamil was added 5 min before the onset of 30 min global normo thermic ischemia followed by 10 min reperfusion. At the conditions of its m aximal cardioprotective effect (heart rate reduction, improved postischemic recovery of left ventricular developed pressure), the hearts were immediat ely used for isolation of sarcolemmal vesicles. In vitro, 1-100 mu mol/l of tedisamil produced a concentration-dependent stimulatory effect on (Na,K)- ATPase activity, with a peak seen at 20 mu mol/l (p < 0.01), while Mg-depen dent ATPase was almost unchanged. Kinetic analysis revealed a significant i ncrease in the affinity of the Na-binding sites on ATPase molecule at 20 mu mol/l of tedisamil. These biochemical findings were confirmed by cytochemi stry. Moreover, ex vivo experiments revealed that tedisamil rendered the sa rcolemmal (Na,K)-ATPase activity to be a more resistant to detrimental effe cts of ischemia. In conclusion, the cardioprotective action of tedisamil wa s accompanied with a better preservation of the specific activity of (Na,K) -ATPase.