Addition of alpha-ketoglutarate to blood cardioplegia improves cardioprotection.
BACKGROUND
We hypothesized that myocardial content of alpha-ketoglutarate (alpha-KG), an intermediate of the Krebs cycle, can be critically low during heart operations, and that provision of alpha-KG could reduce metabolic abnormalities and lead to improved myocardial protection.


METHODS
Twenty-four men aged 46 to 78 years who were undergoing heart operations participated in a prospective, controlled, randomized study. In 13 patients, an average of 28 g of alpha-KG was added to blood cardioplegia. Plasma creatine kinase isoenzyme MB and troponin T, and myocardial extraction of oxygen, substrates, and amino acids were measured.


RESULTS
alpha-Ketoglutarate treatment was associated with lower creatine kinase isoenzyme MB (F = 39.6, df = 1.172, p < 0.001) and lower troponin (F = 12.9, df = 1.172, p < 0.001). The values at 4 hours were 31 +/- 2.4 microg/L versus 49 +/- 4.9 microg/L (creatine kinase isoenzyme MB) and 1.1 +/- 0.05 microg/L versus 2.0 +/- 0.34 microg/L (troponin T). Myocardial oxygen extraction was higher during alpha-KG cardioplegia (p < 0.01), but there were no significant differences in myocardial uptake or release of substrates or amino acids. Lactate release was observed in both groups during cardioplegia. Myocardial lactate release had ceased after 30 minutes of reperfusion in nearly half the alpha-KG-treated patients (6 of 13) but remained in all the control patients (11 of 11, p = 0.016). There were no other differences after 30 minutes of reperfusion.


CONCLUSIONS
Provision of alpha-KG during blood cardioplegia improves myocardial protection in patients undergoing coronary operations. This may be linked to enhanced oxidation.
Kjellman
U W
UW
Department of Thoracic and Cardiovascular Surgery, Sahlgrenska University Hospital, Göteborg, Sweden. rolf.ekroth@hjl.gu.se
Björk
K
K
Ekroth
R
R
Karlsson
H
H
Jagenburg
R
R
Nilsson
F N
FN
Svensson
G
G
Wernerman
J
J
D000368:Aged; D015415:Biomarkers; D002314:Cardioplegic Solutions / Q000494:pharmacology / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D003327:Coronary Disease / Q000628:therapy*; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes; D007656:Ketoglutaric Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011292:Premedication; D013379:Substrate Specificity / Q000187:drug effects; D014336:Troponin / Q000097:blood / Q000187:drug effects; D020107:Troponin T
D015415:Biomarkers; D002314:Cardioplegic Solutions; D007527:Isoenzymes; D007656:Ketoglutaric Acids; D014336:Troponin; D020107:Troponin T; D019344:Lactic Acid; D009020:Morphine; D003402:Creatine Kinase