Faculty Collaboration Database

Cardioprotection during diabetes: the role of mitochondrial DNA. Anesthesiology 2014 Apr;120(4):870-9

Date

12/19/2013

Pubmed ID

24346177

Pubmed Central ID

PMC3975667

DOI

10.1097/ALN.0000000000000107

Scopus ID

2-s2.0-84901722066 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

BACKGROUND: Diabetes alters mitochondrial bioenergetics and consequently disrupts cardioprotective signaling. The authors investigated whether mitochondrial DNA (mtDNA) modulates anesthetic preconditioning (APC) and cardiac susceptibility to ischemia-reperfusion injury by using two strains of rats, both sharing nuclear genome of type 2 diabetes mellitus (T2DN) rats and having distinct mitochondrial genomes of Wistar and fawn-hooded hypertensive (FHH) rat strains (T2DN(mtWistar) and T2DN(mtFHH), respectively).

METHODS: Myocardial infarct size was measured in Wistar, T2DN(mtWistar), and T2DN(mtFHH) rats with or without APC (1.4% isoflurane) in the presence or absence of antioxidant N-acetylcysteine. Flavoprotein fluorescence intensity, a marker of mitochondrial redox state, 5-(and-6)-chloromethyl-2',7'-dichlorofluorescein fluorescence intensity, a marker of reactive oxygen species generation, and mitochondrial permeability transition pore opening were assessed in isolated rat ventricular cardiomyocytes with or without isoflurane (0.5 mmol/l).

RESULTS: Myocardial infarct size was decreased by APC in Wistar and T2DN(mtWistar) rats (to 42 ± 6%, n = 8; and 44 ± 7%, n = 8; of risk area, respectively) compared with their respective controls (60 ± 3%, n = 6; and 59 ± 9%, n = 7), but not in T2DN(mtFHH) rats (60 ± 2%, n = 8). N-acetylcysteine applied during isoflurane treatment restored APC in T2DN(mtFHH) (39 ± 6%, n = 7; and 38 ± 5%, n = 7; 150 and 75 mg/kg N-acetylcysteine, respectively), but abolished protection in control rats (54 ± 8%, n = 6). Similar to the data on infarct size, APC delayed mitochondrial permeability transition pore opening in T2DN(mtWistar) but not in T2DN(mtFHH) cardiomyocytes. Isoflurane increased flavoprotein and 5-(and-6)-chloromethyl-2',7'-dichlorofluorescein fluorescence intensity in all rat strains, with the greatest effect in T2DN(mtFHH) cardiomyocytes.

CONCLUSION: Differences in the mitochondrial genome modulate isoflurane-induced generation of reactive oxygen species which translates into differential susceptibility to APC and ischemia-reperfusion injury in diabetic rats.

Author List

Muravyeva M, Baotic I, Bienengraeber M, Lazar J, Bosnjak ZJ, Sedlic F, Warltier DC, Kersten JR

Author

Maria Y. Muravyeva MD, PhD Assistant Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Anesthetics, Inhalation
Animals
DNA, Mitochondrial
Diabetes Mellitus, Type 2
Disease Models, Animal
Free Radical Scavengers
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Mitochondria, Heart
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
Rats
Rats, Wistar
Reactive Oxygen Species