High extracellular K+ during hypoxic preconditioning episodes attenuates the post-ischemic contractile and ionic...

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 preconditioning's benefits, isolated rat hearts were subjected to two, 5 min hypoxic intervals in the presence of normal K+ (5mM, NmlK-PC) or high K+ (10.3 mM, HiK-PC), separated by 5 min of normoxic reflow. Preconditioning with 5 mM K+ significantly improved developed pressure (DP) after 30 min of ischemia as compared to non-preconditioned control hearts (55.9+/-4.41% v 12.4+/-2.01% of baseline, P<0.05). DP recovery was diminished with 10.3 mM 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+/-1.9 v 19.4+/-2.6 micromol/g dry wt, P=0.09) and was significantly lower than high K+ hearts (22.9+/-1.4 micromol/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+/-10 v 166+/-17 v 155+/-14 micromol/g dry wt, respectively). Thus, the trans-sarcolemmal K+ gradient during the preconditioning period influences preconditioning effects; decreasing the gradient attenuates preconditioning's favorable influences on contractile recovery, cellular K+ loss, and calcium loading during reperfusion.