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Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool.

Wang W, Zhang H, Xue G, Zhang L, Zhang W, Wang L, Lu F, Li H, Bai S, Lin Y, Lou Y, Xu C, Zhao Y - Oxid Med Cell Longev (2014)

Bottom Line: However, IPC protection is ineffective in aged hearts.IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts.Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150086, China.

ABSTRACT

Background: Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool.

Methods: Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol.

Results: IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor, α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

Conclusion: Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.

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Related in: MedlinePlus

(a) Infarct size was measured using tetrazolium chloride (TTC) staining to distinguish necrotic from viable myocardium. (b) Infarct size (expressed as the percentage of risk zone of the total left ventricle [LV]). (c) Lactate dehydrogenase (LDH) released from the coronary effluent in the different groups. The data of infarct size and LDH are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; ▲P < 0.05 versus the Ex-OPC group. ((d)–(h)) The changes in various hemodynamic parameters following reperfusion for 30 min are shown for the young IR control group (YC), young preconditioning group (YPC), old IR control group (OC), old preconditioning group (OPC), exercised old IR control group (Ex-OC), exercised old preconditioning group (Ex-OPC), and DFMO treatment groups (DFMO was administered to the Ex-OC and Ex-OPC groups, resp., presented as the Ex-OC-I and the Ex-OPC-I). Data are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; §P < 0.05 versus Ex-OPC group. LVDP, left ventricular developed pressure; LVEDP, left ventricular end-diastolic pressure; ±dP/dt, maximal positive and negative change in the left ventricular pressure; RPP, rate pressure product.
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fig2: (a) Infarct size was measured using tetrazolium chloride (TTC) staining to distinguish necrotic from viable myocardium. (b) Infarct size (expressed as the percentage of risk zone of the total left ventricle [LV]). (c) Lactate dehydrogenase (LDH) released from the coronary effluent in the different groups. The data of infarct size and LDH are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; ▲P < 0.05 versus the Ex-OPC group. ((d)–(h)) The changes in various hemodynamic parameters following reperfusion for 30 min are shown for the young IR control group (YC), young preconditioning group (YPC), old IR control group (OC), old preconditioning group (OPC), exercised old IR control group (Ex-OC), exercised old preconditioning group (Ex-OPC), and DFMO treatment groups (DFMO was administered to the Ex-OC and Ex-OPC groups, resp., presented as the Ex-OC-I and the Ex-OPC-I). Data are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; §P < 0.05 versus Ex-OPC group. LVDP, left ventricular developed pressure; LVEDP, left ventricular end-diastolic pressure; ±dP/dt, maximal positive and negative change in the left ventricular pressure; RPP, rate pressure product.

Mentions: In young rats, the preconditioning treatment significantly reduced infarct size and LDH release compared with the IR control group [9.6 ± 3.7% versus 35.8 ± 4.2% (YC) of the infarct size and 219.5 ± 79.1 versus 527.1 ± 167.3 U/L (YC) of the LDH activity, respectively, P < 0.05 for all]. In contrast, there was no significant reduction in infarct size and LDH release in the aged hearts upon PC treatment [38.8 ± 6.5% (OPC) versus 46.1 ± 8.2% (OC) of the infarct size and 1036.5 ± 264.5 (OPC) versus 989.5 ± 245.7 U/L (OC) of the LDH activity, resp., P > 0.05 for all]. Compared with the YPC group, the infarct sizes and LDH activity were significantly increased in the OPC groups (OPC versus YPC, P < 0.05, resp.). After exercise, the infarct size of 39.8 ± 2.2% and LDH activity of 943 ± 58.2 U/L in the Ex-OC hearts were reduced to 12.8 ± 2.2% and 248 ± 23.6 U/L in old P hearts (Ex-OPC versus OPC, P < 0.05, resp.). In contrast, the effects of exercise on infarct size and LDH activity were abolished by DFMO (an inhibitor of ODC). DFMO increased the infarct size to 27.4 ± 3.0% and LDH activity to 1333 ± 287.1 U/L with respect to exercised old PC hearts (versus Ex-OPC, P < 0.05 for all) (Figures 2(a), 2(b), and 2(c)).


Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool.

Wang W, Zhang H, Xue G, Zhang L, Zhang W, Wang L, Lu F, Li H, Bai S, Lin Y, Lou Y, Xu C, Zhao Y - Oxid Med Cell Longev (2014)

(a) Infarct size was measured using tetrazolium chloride (TTC) staining to distinguish necrotic from viable myocardium. (b) Infarct size (expressed as the percentage of risk zone of the total left ventricle [LV]). (c) Lactate dehydrogenase (LDH) released from the coronary effluent in the different groups. The data of infarct size and LDH are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; ▲P < 0.05 versus the Ex-OPC group. ((d)–(h)) The changes in various hemodynamic parameters following reperfusion for 30 min are shown for the young IR control group (YC), young preconditioning group (YPC), old IR control group (OC), old preconditioning group (OPC), exercised old IR control group (Ex-OC), exercised old preconditioning group (Ex-OPC), and DFMO treatment groups (DFMO was administered to the Ex-OC and Ex-OPC groups, resp., presented as the Ex-OC-I and the Ex-OPC-I). Data are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; §P < 0.05 versus Ex-OPC group. LVDP, left ventricular developed pressure; LVEDP, left ventricular end-diastolic pressure; ±dP/dt, maximal positive and negative change in the left ventricular pressure; RPP, rate pressure product.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: (a) Infarct size was measured using tetrazolium chloride (TTC) staining to distinguish necrotic from viable myocardium. (b) Infarct size (expressed as the percentage of risk zone of the total left ventricle [LV]). (c) Lactate dehydrogenase (LDH) released from the coronary effluent in the different groups. The data of infarct size and LDH are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; ▲P < 0.05 versus the Ex-OPC group. ((d)–(h)) The changes in various hemodynamic parameters following reperfusion for 30 min are shown for the young IR control group (YC), young preconditioning group (YPC), old IR control group (OC), old preconditioning group (OPC), exercised old IR control group (Ex-OC), exercised old preconditioning group (Ex-OPC), and DFMO treatment groups (DFMO was administered to the Ex-OC and Ex-OPC groups, resp., presented as the Ex-OC-I and the Ex-OPC-I). Data are presented as the mean ± SE (n = 8 per group). *P < 0.05 versus the YC group; †P < 0.05 versus the YPC group; #P < 0.05 versus the Ex-OC group; §P < 0.05 versus Ex-OPC group. LVDP, left ventricular developed pressure; LVEDP, left ventricular end-diastolic pressure; ±dP/dt, maximal positive and negative change in the left ventricular pressure; RPP, rate pressure product.
Mentions: In young rats, the preconditioning treatment significantly reduced infarct size and LDH release compared with the IR control group [9.6 ± 3.7% versus 35.8 ± 4.2% (YC) of the infarct size and 219.5 ± 79.1 versus 527.1 ± 167.3 U/L (YC) of the LDH activity, respectively, P < 0.05 for all]. In contrast, there was no significant reduction in infarct size and LDH release in the aged hearts upon PC treatment [38.8 ± 6.5% (OPC) versus 46.1 ± 8.2% (OC) of the infarct size and 1036.5 ± 264.5 (OPC) versus 989.5 ± 245.7 U/L (OC) of the LDH activity, resp., P > 0.05 for all]. Compared with the YPC group, the infarct sizes and LDH activity were significantly increased in the OPC groups (OPC versus YPC, P < 0.05, resp.). After exercise, the infarct size of 39.8 ± 2.2% and LDH activity of 943 ± 58.2 U/L in the Ex-OC hearts were reduced to 12.8 ± 2.2% and 248 ± 23.6 U/L in old P hearts (Ex-OPC versus OPC, P < 0.05, resp.). In contrast, the effects of exercise on infarct size and LDH activity were abolished by DFMO (an inhibitor of ODC). DFMO increased the infarct size to 27.4 ± 3.0% and LDH activity to 1333 ± 287.1 U/L with respect to exercised old PC hearts (versus Ex-OPC, P < 0.05 for all) (Figures 2(a), 2(b), and 2(c)).

Bottom Line: However, IPC protection is ineffective in aged hearts.IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts.Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150086, China.

ABSTRACT

Background: Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool.

Methods: Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol.

Results: IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor, α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro.

Conclusion: Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.

Show MeSH
Related in: MedlinePlus