Protecting Myocardial Creatine Kinase Activity during Reperfusion Improves Bioenergetics and Contractile Function

Lewis J. Kaplan, Haywood Blum, Anirban Banerjee, Glenn Whitman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)311-315
Number of pages5
JournalJournal of Surgical Research
Volume54
Issue number4
DOIs
Publication statusPublished - Apr 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery

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