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 degrees 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Kaplan
L J
LJ
Division of Cardiothoracic Surgery, Medical College Hospitals--Main Clinical Campus, Philadelphia, Pennsylvania 19129.
Blum
H
H
Banerjee
A
A
Whitman
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology*; D010545:Peroxides / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley
D010545:Peroxides; D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate; D002374:Catalase; D003402:Creatine Kinase