REVERSIBLE INJURY - CREATINE-KINASE RECOVERY RESTORES BIOENERGETICS AND FUNCTION

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 be tween CK activity, mechanical function, and bioenergetics during reper fusion (RP) after a reversible ischemic injury. Rat hearts pretreated for 12 hr without (CTRL) or with myristic acid (MA) underwent 10 min g lobal, 37 degrees C ischemia followed by 10 or 40 min RP while develop ed pressure (DP) was monitored. Catalase and CK were assayed at preisc hemia. CK was also assayed at end ischemia and 10 and 40 min RP. P-31 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). Preischemi c 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, lea ding to a PCr overshoot, Functional recovery and metabolic recovery fo llow return of CK activity, Increased endogenous catalase preserves CK during RP, resulting in normal function and bioenergetics. (C) 1996 A cademic Press, Inc.