Reversible injury: Creatine kinase recovery restores bioenergetics and function

Lewis J. Kaplan, Haywood Blum, Charles F. Bellows, Anirban Banerjee, Glenn J.R. Whitman

Research output: Contribution to journalArticle

Abstract

In postischemic hearts, cytoplasmic creatine kinase (CK) inactivation resulting from toxic oxygen metabolite injury may lead to bioenergetic and mechanical dysfunction. This study determines the relationship between CK activity, mechanical function, and bioenergetics during reperfusion (RP) after a reversible ischemic injury. Rat hearts pretreated for 12 hr without (CTRL) or with myristic acid (MA) underwent 10 min global, 37°C ischemia followed by 10 or 40 min RP while developed pressure (DP) was monitored. Catalase and CK were assayed at preischemia. CK was also assayed at end ischemia and 10 and 40 min RP. 31P nuclear magnetic resonance spectra assessed changes in phosphocreatine (PCr) and adenosine triphosphate (ATP) concentration. Preischemic DP was 95 ± 5 mm Hg. CTRL DP returned to 84 ± 3 by RP10 and 88 ± 6 by RP40 while MA hearts recovered fully by RP10 (90 ± 2). Preischemic catalase activity was significantly increased in MA hearts (1217 ± 36 U/g left ventricular tissue (LV) vs 1007 ± 40 U/g LV, P < 0.01, MA vs CTRL). CTRL CK activity fell from 1870 ± 75 to 1103 ± 11 U/g LV at RP10, but rose to 1272 ± 13 by RP40 (P < 0.01, RP10 vs RP40). MA hearts lost no CK activity during RP. By RP10, CTRL PCr/ATP ratio was elevated to 2.2 ± 0.2 (P < 0.001) from a preischemic level of 1.7 ± 0.4 and normalized by RP40, while MA hearts had a normal PCr/ATP throughout RP. Reversible RP injury transiently depresses mechanical function. Cytoplasmic CK damage during RP impairs PCr utilization, leading to a PCr overshoot. Functional recovery and metabolic recovery follow return of CK activity. Increased endogenous catalase preserves CK during RP, resulting in normal function and bioenergetics.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalJournal of Surgical Research
Volume62
Issue number1
DOIs
StatePublished - Apr 1996
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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