Mitochondrial DNA deletions in coronary artery bypass grafting patients.
OBJECTIVE
Mitochondrial DNA (mitoDNA) deletions have been shown to increase with aging and ischemia and have been suggested to contribute to myocardial dysfunction. The purpose of this study was to determine the prevalence and specificity of mitoDNA deletions in coronary artery bypass patients.


METHODS
Right atrial appendix tissue from 51 cardiac surgical patients (30-93 years; mean 64+/-14 years) was obtained during cardiopulmonary bypass cannulation (Control), just prior to the removal of the venous cannula (Ischemia, 169+/-38 min) and following removal of the cannula (Reperfusion) and used for polymerase chain reaction (PCR) and sequence analysis.


RESULTS
A novel mitoDNA deletion (approximately 7.3 kb, mitoDNA(7.3)) was found in three unrelated, male patients (53, 67, 75 years old). All mitoDNA(7.3) deletion breakpoints were found downstream of the ATP synthase 8 genes and at the 3' end of the cytochrome b genes. The prevalence of the mitoDNA(7.3) deletion was significantly increased (P<0.05) following ischemia and reperfusion. Clinical data indicated that postoperative left ventricular ejection fraction was lower (38.3 vs. 46.4%), and the incidence of previous myocardial infarction higher (1.7 vs. 0.6) in patients exhibiting mitoDNA deletions.


CONCLUSIONS
Our results reveal a novel mitochondrial DNA deletion occurring within the genome region coding for the mitochondrial genes of oxidative phosphorylation that is significantly increased during ischemia and reperfusion. The incidence and prevalence of mitoDNA(7.3) deletions in patients with clinical indications of poor recovery suggests that mitoDNA(7.3) deletions may provide an important indicator to surgical outcome in the cardiac surgical patient.
Levitsky
Sidney
S
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Room 144, 02115, Boston, MA, USA
Laurikka
Jari
J
Stewart
Robert D
RD
Campos
Christian T
CT
Lahey
Steven J
SJ
McCully
James D
JD
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D045303:Cytochromes b / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011184:Postoperative Period; D011379:Prognosis; D013318:Stroke Volume; D016896:Treatment Outcome
D004272:DNA, Mitochondrial; D045303:Cytochromes b; D025261:Mitochondrial Proton-Translocating ATPases