TY - JOUR
T1 - Reversible injury
T2 - Creatine kinase recovery restores bioenergetics and function
AU - Kaplan, Lewis J.
AU - Blum, Haywood
AU - Bellows, Charles F.
AU - Banerjee, Anirban
AU - Whitman, Glenn J.R.
N1 - Funding Information:
1This work was supported by NIH Grant HL 42922.
PY - 1996/4
Y1 - 1996/4
N2 - 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.
AB - 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.
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U2 - 10.1006/jsre.1996.0181
DO - 10.1006/jsre.1996.0181
M3 - Article
C2 - 8606495
AN - SCOPUS:0029664575
SN - 0022-4804
VL - 62
SP - 103
EP - 108
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -