Key result
Isoflurane preconditioning decreased left ventricular end-diastolic pressure from 35 to 23 mmHg in control mice, but this cardioprotective effect was lost in type 2 diabetic mice.
The failure of isoflurane-induced cardiac preconditioning in type 2 diabetic mice is linked to aberrant regulation of microRNA-21, eNOS, and mitochondrial complex I.
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Isoflurane preconditioning cardioprotection appears lost in diabetic mice; this level 5 animal study leaves open relevance to human perioperative care.
BACKGROUND: 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 2 diabetic mice. METHODS: 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. RESULTS: 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. CONCLUSIONS: Failure of isoflurane cardiac preconditioning in obese type 2 diabetic db/db mice is associated with aberrant regulation of microRNA-21, endothelial nitric-oxide synthase, and mitochondrial respiratory complex I.
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Ge et al. (2017) studied Myocardial ischemia/reperfusion injury in type 2 diabetes. Isoflurane vs. Absence of isoflurane was evaluated on Left ventricular end-diastolic pressure 2 h after post-ischemic reperfusion in C57BL/6 mice (p=0.019). Isoflurane preconditioning decreased left ventricular end-diastolic pressure from 35 to 23 mmHg in control mice, but this cardioprotective effect was lost in type 2 diabetic mice.
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