High Extracellular K+During Hypoxic Preconditioning Episodes Attenuates the Post-Ischemic Contractile and Ionic Benefits of Preconditioning

Hypoxic preconditioning improves contractile recovery and decreases calcium loading following ischemia and reperfusion. To test whether changing the trans-sarcolemmal K+gradient during the preconditioning period changes preconditioningʹs benefits, isolated rat hearts were subjected to two, 5 min hypoxic intervals in the presence of normal K+(5m , NmlK-PC) or high K+(10.3 m , HiK-PC), separated by 5 min of normoxic reflow. Preconditioning with 5 m K+significantly improved developed pressure (DP) after 30 min of ischemia as compared to non-preconditioned control hearts (55.9±4.41%v12.4±2.01% of baseline,P<0.05). DP recovery was diminished with 10.3 m K+(25.1±4.20% of baseline,P<0.05). At the end of reperfusion, cell Ca2+trended lower in hypoxic preconditioned hearts compared with control hearts (12.9±1.9v19.4±2.6μmol/g dry wt,P=0.09) and was significantly lower than high K+hearts (22.9±1.4μmol/g dry wt,P<0.006). Intracellular K+during reperfusion was significantly higher in preconditioned compared with control hearts (P<0.02) and high K+hearts (P<0.002) (231±10v166±17v155±14μmol/g dry wt, respectively). Thus, the trans-sarcolemmal K+gradient during the preconditioning period influences preconditioning effects; decreasing the gradient attenuates preconditioningʹs favorable influences on contractile recovery, cellular K+loss, and calcium loading during reperfusion.