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 preconditioning's benefits, isolated rat hearts were subjected to two, 5 min hypoxic intervals in the presence of normal K⁺ (5 mM, 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 μmol/g dry wt, P = 0.09) and was significantly lower than high K⁺ hearts (22.9 ± 1.4 μmol/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 μmol/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.