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Hypothermic protection of ischemic heart: 13 C NMR substrate analysis
Author(s) -
Hyyti Outi Maria,
Ning XueHan,
Portman Michael A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1377-a
Subject(s) - hypothermia , chemistry , hydrogen peroxide , medicine , substrate (aquarium) , oxidative stress , ischemia , metabolism , biochemistry , biology , ecology
Mechanisms for changes in myocardial metabolism in hypothermic protection stay unclear, though substrate contribution into citric acid cycle (CAC) may play a role. Specifically, acetoacetate (AA) has been shown to have antioxidant capabilities. We studied hypothermic protection and substrate contribution into CAC in heart. Isolated rat hearts formed 3 groups: control ( C , 37°C, n=5), ischemic ( IS , 37°C, n=5) and hypothermic ischemic ( HIS , 28°C, n=3). HIS hearts were held at 28°C 25 min prior to and during 45 min cardioplegic arrest, after which all ischemic hearts were reperfused in 37°C. Perfusate included physiological concentrations of 13 C labeled substrates: 1,3‐AA, 3‐lactate, U‐mixed free fatty acids, unlabeled glucose. 13 C NMR isotopomer analysis yielded fractional contributions (Fc) of substrates to CAC. HIS hearts tended to have a higher left ventricular developed pressure, pressure rate product and oxygen consumption at 35 min of reperfusion vs. IS . Fc of AA tended to increase in IS vs. C (0.33±0.02, 0.27±0.02, respectively). However, Fc of AA in HIS (0.25±0.03) was similar to C . Hypothermia improved cardiac function with C levels of AA Fc. Increased AA oxidation in IS might hinder detoxification of hydrogen peroxide produced by ischemia causing myocardial injury. These results suggest a link between AA oxidation and hypothermic protection. Support: NIH HL60666.