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Isoflurane preconditioning confers cardioprotection by activation of ALDH2.

Lang XE, Wang X, Zhang KR, Lv JY, Jin JH, Li QS - PLoS ONE (2013)

Bottom Line: Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide.Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2.In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China.

ABSTRACT
The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury.

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The influence of anesthetic-induced preconditioning with 1.0 MAC of isoflurane on leakage of LDH and CK-MB, and infarct area in rat hearts.A, B. Serum LDH and CK-MB concentrations were analyzed. The increase in LDH and CK-MB concentrations was lower in rats pretreated with isoflurane than in I/R group. C. Isoflurane preconditioning significantly decreased infarct area compared with I/R group animals. Representative cross-sectional slices derived from a single heart with and without isoflurane. The infarct size normalized to the area at risk. Values are means ± S.E.M., n = 5 in each group. *P<0.05, **P<0.01 vs. sham group, and #P<0.05 vs. the I/R control group.
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pone-0052469-g001: The influence of anesthetic-induced preconditioning with 1.0 MAC of isoflurane on leakage of LDH and CK-MB, and infarct area in rat hearts.A, B. Serum LDH and CK-MB concentrations were analyzed. The increase in LDH and CK-MB concentrations was lower in rats pretreated with isoflurane than in I/R group. C. Isoflurane preconditioning significantly decreased infarct area compared with I/R group animals. Representative cross-sectional slices derived from a single heart with and without isoflurane. The infarct size normalized to the area at risk. Values are means ± S.E.M., n = 5 in each group. *P<0.05, **P<0.01 vs. sham group, and #P<0.05 vs. the I/R control group.

Mentions: Regional myocardial ischemia for 40 min by LAD ligation followed by 120 min of reperfusion markedly increased the leakage of LDH (Figure 1A) and CK-MB (Figure 1B) compared to sham controls. Isoflurane-induced APC significantly reduced the I/R-induced increase in LDH and CK-MB release in rat heart.


Isoflurane preconditioning confers cardioprotection by activation of ALDH2.

Lang XE, Wang X, Zhang KR, Lv JY, Jin JH, Li QS - PLoS ONE (2013)

The influence of anesthetic-induced preconditioning with 1.0 MAC of isoflurane on leakage of LDH and CK-MB, and infarct area in rat hearts.A, B. Serum LDH and CK-MB concentrations were analyzed. The increase in LDH and CK-MB concentrations was lower in rats pretreated with isoflurane than in I/R group. C. Isoflurane preconditioning significantly decreased infarct area compared with I/R group animals. Representative cross-sectional slices derived from a single heart with and without isoflurane. The infarct size normalized to the area at risk. Values are means ± S.E.M., n = 5 in each group. *P<0.05, **P<0.01 vs. sham group, and #P<0.05 vs. the I/R control group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585331&req=5

pone-0052469-g001: The influence of anesthetic-induced preconditioning with 1.0 MAC of isoflurane on leakage of LDH and CK-MB, and infarct area in rat hearts.A, B. Serum LDH and CK-MB concentrations were analyzed. The increase in LDH and CK-MB concentrations was lower in rats pretreated with isoflurane than in I/R group. C. Isoflurane preconditioning significantly decreased infarct area compared with I/R group animals. Representative cross-sectional slices derived from a single heart with and without isoflurane. The infarct size normalized to the area at risk. Values are means ± S.E.M., n = 5 in each group. *P<0.05, **P<0.01 vs. sham group, and #P<0.05 vs. the I/R control group.
Mentions: Regional myocardial ischemia for 40 min by LAD ligation followed by 120 min of reperfusion markedly increased the leakage of LDH (Figure 1A) and CK-MB (Figure 1B) compared to sham controls. Isoflurane-induced APC significantly reduced the I/R-induced increase in LDH and CK-MB release in rat heart.

Bottom Line: Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide.Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2.In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China.

ABSTRACT
The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury.

Show MeSH
Related in: MedlinePlus