Protecting myocardial creatine kinase activity during reperfusion improves bioenergetics and contractile function

The exact mechanisms underlying reperfusion (RP) injury are unclear but are thought to involve toxic oxygen metabolites such as H₂O₂. The purpose of our study was to determine whether increasing endogenous catalase (CAT) stores would protect creatine kinase (CK) activity and improve bioenergetics and mechanical function during RP. Rats (n = 6/group) were pretreated with myristic acid (MA) or nothing 6 to 12 hr prior to cardiectomy. Hearts were Langendorff perfused and developed pressure (DP) was monitored during 25 min of 37°C ischemia and 10 or 40 min of RP. CK activity was determined at baseline, end ischemia, and 40 min RP. CAT activity and H₂O₂ production was assayed at baseline, end ischemia, and 10 min RP. ³¹P NMR spectra were continuously acquired to determine ATP and phosphocreatine (PCr) concentrations. MA-pretreated hearts demonstrated elevated CAT stores (121 ± 4%, P < 0.05). No H₂O₂ was produced during ischemia, and both groups generated significant but equal amounts of H₂O₂ at RP 10 (P < 0.001 vs preischemia (PI), P = NS between groups). By RP 40, MA-pretreated hearts recovered more DP than did control hearts (75 ± 5% of PI vs 35 ± 4% of PI, P < 0.001) and retained more CK activity as well (66 ± 4% vs 52 ± 2%, P <.05). PCr/ATP ratios of control hearts were abnormally elevated above baseline and that of MA hearts during RP (2.4 ± 0.1 vs 1.85 ± 0.08, P < 0.05 at RP 40). We conclude that: (1) only RP generates H₂O₂, (2) CK inactivation occurs during RP, (3) MA augments endogenous CAT and protects CK during RP, and (4) enhanced CK activity results in improved mechanical and bioenergetic recovery.