Myocyte endothelin exposure during cardioplegic arrest exacerbates contractile dysfunction after reperfusion

Transient left ventricular (LV) dysfunction can occur after cardioplegic ar rest. The contributory mechanisms for this phenomenon are not completely un derstood. We tested the hypothesis that exposure of LV myocytes to endothel in (ET) during simulated cardioplegic arrest would have direct effects on c ontractile processes with subsequent reperfusion. LV porcine myocytes were randomly assigned to three groups: 1) Control: normothermic (37 degrees C) cell media (n = 204); 2) Cardioplegia: simulated cardioplegic arrest (K+ 24 mEq/L, 4 degrees C x 2 h) followed by reperfusion and rewarming with cell media (n = 164); and 3) Cardioplegia/ET: simulated cardioplegic arrest in t he presence of ET (200 pM) followed by reperfusion with cell media containi ng ET (n = 171). Myocyte contractility was measured by computer-assisted vi deo microscopy. In a subset of experiments, myocyte intracellular calcium w as determined after Fluo-3 (Molecular Probes, Eugene, OR) loading by digita l fluorescence image analysis. Myocyte shortening velocity was reduced afte r cardioplegic arrest compared with controls (52 +/- 2 vs 84 +/- 3 mu m/s, respectively; P < 0.05) and was further reduced with cardioplegic arrest an d ET exposure (43 +/- 2 mu m/s, P < 0.05). Intracellular calcium was signif icantly increased in myocytes exposed to cardioplegia compared with normoth ermic control myocytes and was further augmented by cardioplegia with ET su pplementation (P < 0.05). Exposure of the LV myocyte to ET during cardiople gic arrest directly contributed to contractile dysfunction after reperfusio n. Moreover, alterations in intracellular calcium may play a role in potent iatiing the myocyte contractile dysfunction associated with 1 ET exposure d uring cardioplegic arrest.