ROS are required for rapid reactivation of Na<sup>+</sup>/Ca<sup>2+</sup>exchanger in hypoxic reoxygenated guinea pig ventricular myocytes

Eigel, B. N.; Gursahani, H.; Hadley, R. W.

doi:10.1152/ajpheart.00721.2003

Cited by 71 publications

(45 citation statements)

References 35 publications

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“…The increase in pAKT and Bcl-xL after fetal exposure exposure to propofol is thought to lead to lower levels of cytochrome c being released from the mitochondria, and consequently to less activation of caspase-9 and caspase-3 in fetal hearts. Some previous studies have demonstrated that the level of phosphorylated AKT may reflect its activity under conditions such as preconditioning (24) and postconditioning (23). Therefore, the findings of our study suggest that propofol administration to the mother and to the fetus at the onset of reperfusion for 8 h might attenuate myocardial apoptosis, partly through maintaining or even increasing the activity of the phosphoinositide-3-kinase/AKT pathway.…”

Section: Discussionsupporting

confidence: 51%

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Propofol administration to the fetal–maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest

et al. 2013

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Background: cardiac dysfunction is reported to occur after severe perinatal asphyxia. We hypothesized that anesthesia of the mother with propofol during emergency cesarean section (c-section) would result in less cardiac injury (troponin T) in preterm fetuses exposed to global severe asphyxia in utero than anesthesia with isoflurane. We tested whether propofol decreases the activity of proapoptotic caspase-3 by activating the antiapoptotic AKT kinase family and the signal transducer and activator of transcription-3 (sTAT-3). Methods: Pregnant ewes were randomized to receive either propofol or isoflurane anesthesia. A total of 44 late-preterm lambs were subjected to in utero umbilical cord occlusion (UcO), resulting in asphyxia and cardiac arrest, or sham treatment. After emergency c-section, each fetus was resuscitated, mechanically ventilated, and supported under anesthesia for 8 h using the same anesthetic as the one received by its mother. results: At 8 h after UcO, the fetuses whose mothers had received propofol anesthesia had lower plasma troponin T levels, and showed a trend toward a higher median left ventricular ejection fraction (LVeF) of 84% as compared with 74% for those whose mothers had received isoflurane. Postasphyxia activation of caspase-3 was lower in association with propofol anesthesia than with isoflurane. Postasphyxia levels of sTAT-3 and the AKT kinase family rose 655% and 500%, respectively with the use of propofol anesthesia for the mother. conclusion: The use of propofol for maternal anesthesia results in less cardiac injury in late-preterm lambs subjected to asphyxia than the use of isoflurane anesthesia. The underlying mechanism may be activation of the antiapoptotic sTAT-3 and AKT pathways. Multi-organ dysfunction is a common outcome of severe perinatal asphyxia (1,2). One of the organs significantly involved in the fate of the asphyctic newborn is the heart (3,4); it can compromise the oxygen supply of other organs, resulting in irreversible injury (5). It is therefore important to maintain adequate cardiac function in neonates who have undergone an asphyxic insult. Currently, the only available therapy for cardiac function in the neonatal setting after an ischemic insult consists in treatment with positive inotropic and/or vasoactive drugs. The impact of this measure is limited because it neither prevents nor attenuates the degree of the initial myocardial ischemic injury (6,7). Evidence has now accumulated that some anesthetics such as propofol are cardioprotective in adult patients exposed to myocardial ischemia (8)(9)(10), and that this propofol-related cardioprotection is mediated through the activation of signal transducer and activator of transcription (STAT)-3 and phosphoinositide-3-kinase/AKT (11). Isoflurane, a volatile anesthetic, also protects the adult heart from ischemia and reperfusion injury by intervening with the mitochondrial apoptosis pathway (12,13). Both anesthetics are rapid acting and reliable and are therefore used when prompt delivery of the fetus becomes e...

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Section: Discussionsupporting

confidence: 51%

“…Wang et al provided evidence that propofol might interfere with apoptotic pathways through activation of AKT (11). Activated AKT blocks apoptosis by phosphorylating its substrates, such as Bcl-2-associated death protein (Bad) (23). The latter, in turn, modulates Bcl-xL, an antiapoptotic protein (19).…”

Section: Discussionmentioning

confidence: 99%

Propofol administration to the fetal–maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest

et al. 2013

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“…ROS, including O 2 − , H 2 O 2 , and •OH, are produced mainly in cardiac pathological conditions such as ischemia / reperfusion injury (2); and they are required for rapid reactivation of NCX in hypoxic reoxygenated guinea-pig ventricular myocytes (37). I NCX is inhibited by acidosis and enhanced by alkalosis (29).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Na+/Ca2+ Exchanger Activation by Hydrogen Peroxide in Guinea-Pig Ventricular Myocytes

et al. 2007

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Abstract. Using the whole-cell voltage clamp, we examined the mechanism of activation of the Na + / Ca 2+ exchanger (NCX) by hydrogen peroxide (H 2 O 2 ) in isolated guinea-pig cardiac ventricular myocytes. Exposure to H 2 O 2 increased the NCX current. The effect was inhibited by cariporide, an inhibitor of the Na + / H + exchanger (NHE), suggesting that there are NHEdependent and -independent pathways in the effect of H 2 O 2 on NCX. In addition, both pathways were blocked by edaravone, a hydroxyl radical (•OH) scavenger; pertussis toxin, a Gα i / o protein inhibitor; and U0126, an inhibitor of mitogen-activated protein kinase / extracellular signalregulated kinase kinase (MEK). On the other hand, wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, inhibited only the NHE-dependent pathway, while PP2, a Src family protein tyrosine kinase inhibitor, inhibited only the NHE-independent pathway. Taken together, our data suggest that H 2 O 2 increases the NCX current via two signal transduction pathways. The common pathway is the conversion of H 2 O 2 to •OH, which activates Gα i / o protein and a mitogen-activated protein (MAP) kinase signaling pathway. Then, one pathway activates NHE with a PI3K-dependent mechanism and indirectly increases the NCX current. Another pathway involves activation of a Src family tyrosine kinase.

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“…The activity of the cardiac NCX is sensitive to modification by ROS. Indeed, NCX activity is profoundly inhibited by hypoxia in guinea pig ventricular myocytes, but is reactivated within 1-2 min of reoxygenation possibly due to rising ROS (70). Similarly, H 2 O 2 perfusion or ROS generation by XOR system induced NCX activity in rabbit ventricular myocytes (90).…”

Section: B Plasmalemmal Camentioning

confidence: 99%

Redox Control of Cardiac Excitability

Aggarwal

Makielski

2013

Antioxidants & Redox Signaling

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Reactive oxygen species (ROS) have been associated with various human diseases, and considerable attention has been paid to investigate their physiological effects. Various ROS are synthesized in the mitochondria and accumulate in the cytoplasm if the cellular antioxidant defense mechanism fails. The critical balance of this ROS synthesis and antioxidant defense systems is termed the redox system of the cell. Various cardiovascular diseases have also been affected by redox to different degrees. ROS have been indicated as both detrimental and protective, via different cellular pathways, for cardiac myocyte functions, electrophysiology, and pharmacology. Mostly, the ROS functions depend on the type and amount of ROS synthesized. While the literature clearly indicates ROS effects on cardiac contractility, their effects on cardiac excitability are relatively under appreciated. Cardiac excitability depends on the functions of various cardiac sarcolemal or mitochondrial ion channels carrying various depolarizing or repolarizing currents that also maintain cellular ionic homeostasis. ROS alter the functions of these ion channels to various degrees to determine excitability by affecting the cellular resting potential and the morphology of the cardiac action potential. Thus, redox balance regulates cardiac excitability, and under pathological regulation, may alter action potential propagation to cause arrhythmia. Understanding how redox affects cellular excitability may lead to potential prophylaxis or treatment for various arrhythmias. This review will focus on the studies of redox and cardiac excitation. Antioxid. Redox Signal. 18, 432-468.

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ROS are required for rapid reactivation of Na⁺/Ca²⁺exchanger in hypoxic reoxygenated guinea pig ventricular myocytes

Cited by 71 publications

References 35 publications

Propofol administration to the fetal–maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest

Propofol administration to the fetal–maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest

Mechanism of Na+/Ca2+ Exchanger Activation by Hydrogen Peroxide in Guinea-Pig Ventricular Myocytes

Redox Control of Cardiac Excitability

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ROS are required for rapid reactivation of Na+/Ca2+exchanger in hypoxic reoxygenated guinea pig ventricular myocytes

Cited by 71 publications

References 35 publications

Propofol administration to the fetal–maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest

Propofol administration to the fetal–maternal unit reduces cardiac injury in late-preterm lambs subjected to severe prenatal asphyxia and cardiac arrest

Mechanism of Na+/Ca2+ Exchanger Activation by Hydrogen Peroxide in Guinea-Pig Ventricular Myocytes

Redox Control of Cardiac Excitability

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ROS are required for rapid reactivation of Na⁺/Ca²⁺exchanger in hypoxic reoxygenated guinea pig ventricular myocytes