Failure of Isoflurane Cardiac Preconditioning in Obese Type 2 Diabetic Mice
Involves Aberrant Regulation of MicroRNA-21, Endothelial Nitric-oxide Synthase,
and Mitochondrial Complex I.
Authors Ge ZD, Li Y, Qiao S, Bai X, Warltier DC, Kersten JR, Bosnjak ZJ, Liang M
Submitted By Mingyu Liang on 11/8/2017
Status Published
Journal Anesthesiology
Year 2017
Date Published 10/1/2017
Volume : Pages Not Specified : Not Specified
PubMed Reference 29040168
Abstract Diabetes impairs the cardioprotective effect of volatile anesthetics, yet the
mechanisms are still murky. We examined the regulatory effect of isoflurane on
microRNA-21, endothelial nitric-oxide synthase, and mitochondrial respiratory
complex I in type II diabetic mice., Myocardial ischemia/reperfusion injury was
produced in obese type 2 diabetic (db/db) and C57BL/6 control mice ex vivo in
the presence or absence of isoflurane administered before ischemia. Cardiac
microRNA-21 was quantified by real-time quantitative reverse
transcriptional-polymerase chain reaction. The dimers and monomers of
endothelial nitric-oxide synthase were measured by Western blot analysis.
Mitochondrial nicotinamide adenine dinucleotide fluorescence was determined in
Langendorff-perfused hearts., Body weight and fasting blood glucose were greater
in db/db than C57BL/6 mice. Isoflurane decreased left ventricular end-diastolic
pressure from 35 ± 8 mmHg in control to 23 ± 9 mmHg (P = 0.019, n = 8
mice/group, mean ± SD) and elevated ±dP/dt 2 h after post-ischemic reperfusion
in C57BL/6 mice. These beneficial effects of isoflurane were lost in db/db mice.
Isoflurane elevated microRNA-21 and the ratio of endothelial nitric-oxide
synthase dimers/monomers and decreased mitochondrial nicotinamide adenine
dinucleotide levels 5 min after ischemia in C57BL/6 but not db/db mice.
MicroRNA-21 knockout blocked these favorable effects of isoflurane, whereas
endothelial nitric-oxide synthase knockout had no effect on the expression of
microRNA-21 but blocked the inhibitory effect of isoflurane preconditioning on
nicotinamide adenine dinucleotide., Failure of isoflurane cardiac
preconditioning in obese type II diabetic db/db mice is associated with aberrant
regulation of microRNA-21, endothelial nitric-oxide synthase, and mitochondrial
respiratory complex I.