Decrease in Ischemic Tolerance with Aging in Isolated Perfused Fischer 344 Rat Hearts: Relation to Increases in Intracellular Na+After Ischemia

Tani, Masato; Suganuma, Yukako; Hasegawa, Hiroshi; Shinmura, Ken; Ebihara, Yoshinori; Hayashi, Yujiro; Guo, Xiao Dong; Takayama, M.

doi:10.1006/jmcc.1997.0533

Cited by 58 publications

(32 citation statements)

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“…Intracellular protons are extruded from the cells by the Na + /H + exchanger (NHE-1 in the heart) that favors firstly intracellular sodium accumulation and secondly cellular calcium entry through the Na + /Ca 2+ exchanger (Sniecinski and Liu 2004) when deprivation of ATP does not allow functioning of the Na + /K + -ATPase. Middle-aged and senescent hearts have been characterized by increased cellular sodium accumulation at the end of ischemia (Tani et al 1997 and compared with young hearts. They are protected against reperfusion-induced cellular damage by either the NHE-1 inhibitor cariporide (Nakai et al 2002;Besse et al 2004;Simm et al 2008) or the Na + /Ca 2+ exchanger (NCX) inhibitor KB-R7943 (Yamamura et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

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Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10-or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H 2 O 2 release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H 2 O 2 when they oxidize FADH 2 -linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration AGE (2011) of the coronary perfusion was explained by an increased mitochondrial ROS release related to the preservation of complex II activity during reperfusion.

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Section: Discussionmentioning

confidence: 99%

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

View full text Add to dashboard Cite

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“…Rats of 52 wk of age were anesthetized with an intraperitoneal injection of pentobarbital sodium (40 mg/kg). Hearts were excised quickly and perfused with modified Krebs-Henseleit buffer gassed with 95% O 2-5% CO2 at 37°C according to the Langendorff procedure (42,45,46). The coronary perfusion pressure was maintained at 70 mmHg.…”

Section: Methodsmentioning

confidence: 99%

“…Pacing was turned off during global ischemia and turned on 10, 20, and 30 min after reperfusion to measure the recovery of LV function. Indexes of LV function [LV systolic pressure (LVSP); LV developed pressure (LVDP; equal to LVSP Ϫ LVEDP); and LV peak positive and negative dP/dt] were recorded as previously described (42,45,46).…”

Section: Methodsmentioning

confidence: 99%

“…Most investigations have concluded that myocardial ischemic tolerance decreases with age (7,20,45). In addition, several experimental and clinical investigations have addressed the issue of whether IPC occurs in aged hearts (1,2,28,40,46).…”

Section: Effect Of Cr On Myocardial Ischemia-reperfusion Injury and Ipcmentioning

confidence: 99%

“…Hearts from senescent animals are more susceptible to ischemia than those from young animals (7,20,45). Recently, a number of investigators have demonstrated that the cardioprotective effect of ischemic preconditioning (IPC) is impaired in aged animals (1,2,28,40,46).…”

mentioning

confidence: 99%

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Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Shinmura

Tamaki

Bolli

2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

114

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Ischemic tolerance decreases with aging, and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in middle-aged animals. We have demonstrated that short-term caloric restriction (CR) improves myocardial ischemic tolerance in young and old animals via the activation of adiponectin-AMP-activated protein kinase (AMPK)-mediated signaling. However, it is unknown whether prolonged CR confers cardioprotection in a similar manner. Furthermore, little is known regarding the myocardial expression of silent information regulator 1 (Sirt1; which reportedly mediates various aspects of the CR response) with prolonged CR. Thus, 6-mo-old male Fischer-344 rats were randomly divided into ad libitum (AL) and CR groups. Six months later, isolated perfused hearts were subjected to 25 min of global ischemia followed by 120 min of reperfusion with or without IPC. CR improved the recovery of left ventricular function and reduced infarct size after ischemiareperfusion and restored the IPC effect. Serum adiponectin levels increased, but myocardial levels of total and phosphorylated AMPK did not change with prolonged CR. Total levels of Sirt1 did not change with CR; however, in the nuclear fraction, CR significantly increased Sirt1 and decreased acetyl-histone H3. Eleven rats from each group were given N-nitro-L-arginine methyl ester in their drinking water for 4 wk before death. In these hearts, chronic inhibition of nitric oxide synthase prevented the increase in nuclear Sirt1 content by CR and abrogated CR-induced cardioprotection. These results demonstrate that 1) prolonged CR improves myocardial ischemic tolerance and restores the IPC effect in middle-aged rats and 2) CR-induced cardioprotection is associated with a nitric oxidedependent increase in nuclear Sirt1 content. aging; myocardial ischemia; nutrition; preconditioning; reperfusion injury; silent information regulator 1

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Mitochondria in the Aging Heart

Marı́n-Garcı́a

2012

Mitochondria and Their Role in Cardiovascular Disease

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Decrease in Ischemic Tolerance with Aging in Isolated Perfused Fischer 344 Rat Hearts: Relation to Increases in Intracellular Na+After Ischemia

Cited by 58 publications

References 0 publications

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Mitochondria in the Aging Heart

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