Garrett Gross

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..3% ± 1.3%). The 2 EET antagonists completely blocked capsaicin-induced cardioprotection. These results clearly suggest that EETs mediate RPCT-, bradykinin- and capsaicin-induced cardioprotection in rat hearts...

..Eribis peptide 94 (EP 94) is a new enkephalin derivative which potently binds to the µ- and δ-opioid receptor. In this study, we determined the effects of EP 94 and potential mechanism(s) involved in cardioprotection of the rat heart...

..These results suggest that EP 94 reduces infarct size (expressed as a percent of the area at risk) in the rat primarily via activation of central μ opioid receptors...

..These data suggest that OIC occurs via the JAK2 regulation of PI3K pathway-dependent STAT3, Akt, and GSK-3 beta, with GSK-3 beta contributing a central role in acute OIC...

..The therapeutic potential of increasing EET concentrations and/or reducing 20-HETE concentrations will also be addressed...

..8%). These data suggest that inhibition of adenosine kinase is effective in reducing infarct development via A(1)AR, A(3)AR and DOR activation. Data also suggest that this protection is mediated via ROS, PKC-delta and mitoK(ATP) channels...

..These data suggest that FIT has a prolonged cardioprotective window greater than that of any previously described cardioprotective agent that requires PI3K primarily in the trigger phase but also partially, as a mediator or end effector...

..These data also suggest that vasodilatory responses to AA in the dog are primarily COX-1 dependent. Selective COX-2 inhibition does not affect either prostacyclin or nitric oxide mediated vasodilation in the canine coronary circulation...

..Furthermore, acute aspirin administration has a detrimental interaction with morphine that abrogates morphine-induced infarct size reduction...

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..Hence, GSK inhibition reduces infarct size when given 24 h before the administration via the opening K(ATP) channels and MPTP closure...

..These data also suggest that 14,15-EEZE is not blocking the mitochondrial ATP-sensitive potassium channel as a mechanism for antagonizing the cardioprotective effects of the EETs...

..These results suggest a unique role for endogenous EETs in both IPC and POC...

..Taken together, these results suggest that the major cardioprotective effects of the EETs depend on activation of a G(i/o) protein-coupled delta- and/or kappa-opioid receptor...

..The epoxyeicosatrienoic acids (EETs) have also recently been shown to be antinociceptive and have been shown to mimic ischemic preconditioning (IPC) and postconditioning (POC) in dogs, therefore, we tested the role of the EETs in RPCT...

..Furthermore, no differences were seen in phosphorylation of GSKalpha (Ser21 or Tyr279) or phosphorylation of GSKbeta (Tyr216). These data indicate that OIC occurs via the phosphorylation of GSKbeta at Ser9 during reperfusion...

..These results and others obtained in models of myocardial stunning and hypertrophy suggest that inhibitors of EPHX2 or sEH have therapeutic potential in a broad range of cardiovascular diseases...

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..6;; 49.4+/-1.7;, 61.6+/-1.6%, respectively, * or ; P<0.001). These data indicate that both the sK(ATP) and mK(ATP) channel are involved in acute OIC and the GSK signaling axis regulates cardioprotection via K(ATP) channel opening...

..To date, this is the first demonstration that opioids and volatile anesthetics work in conjunction to confer protection against myocardial infarction through potentiation of cardiac K(ATP) channel opening...

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..It appears that the trigger effect is not dependent on the activity of iNOS or COX-2 but the late phase of cardioprotection is dependent on the upregulation of these enzymes...

..We conclude that both mitochondrial and sarcolemmal K(ATP) channels contribute to isoflurane-induced delayed cardioprotection...

..We conclude that CP-532,903 is a highly selective agonist of the mouse A(3)AR that protects against ischemia/reperfusion injury by activating sarcolemmal K(ATP) channels...

..0 +/- 5.0 vs. 29.2 +/- 4.7%, respectively; P </= 0.001). These data suggest that the sK(ATP) channel is required as a trigger but not a mediator for delayed IPC-induced infarct size reduction in rat hearts...

..Finally, the protective effects of EETs are mediated by cardiac K(ATP) channels...

..These data suggest that SNC-121 appears to enhance message and subsequently the activity and expression of 12-LO protein during times of stress, resulting in delayed cardioprotection...

..The full text of this article is available online at http://circres.ahajournals.org...

..These data demonstrate that Cl-IB-MECA protects against myocardial ischemia/reperfusion injury in mice principally by activating the A(3)AR...

..Receptor cross-talk between ligands and the common signaling pathways involved for these ligands will also be briefly discussed...

..The mechanism appears to be a non-opioid receptor mediated production of reactive oxygen species that triggers the signaling cascade leading to delayed cardioprotection...

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..These results suggest there may be a link between the endogenous release of opioids and HS that mediates cardioprotection...

..These data suggest that exogenous activation of delta- and kappa-opioid receptors afford protection against myocardial stunning in the isolated murine heart, an effect attenuated by selective receptor antagonists...

..These data suggest that PKC-delta does not play an important role in IPC and that differences in isoform importance are evident during pharmacological versus ischemia-induced preconditioning...

..05 vs. untreated) in both young and senescent hearts. These data demonstrate that aged hearts maintain the ability to be preconditioned by chronic exposure to morphine in the absence of acute protection...

..This is not meant to completely rule out other receptors since it is clear that IPC is a phenomenon with multiple pathways that appear to be responsible for the cardioprotection observed...

..2+/-3, P<0.001). Pretreatment with naloxone significantly attenuated the protective effects of MPC (53.8+/-4, P<0.0002). Therefore, it appears that MPC releases endogenous opioids that protect the myocardium from ischemic injury...

..We conclude that cardioprotection conferred by adaptation to hypoxia from birth persists on subsequent exposure to normoxia and is associated with enhanced NOS activity and activation of K(ATP) channels...

..CONCLUSIONS: These data demonstrate that chronic exposure to morphine unexpectedly results in a profound and persistent cardioprotective phenotype...

..2+/-4.5). These results suggest that opioid receptors are important in IPC in dogs, and stimulation of delta-opioid receptors with selective agonists can mimic the cardioprotective effects of IPC and may have therapeutic potential...

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..Thrombopoietin (Tpo) is known for its ability to stimulate platelet production. However, it is currently unknown whether Tpo plays a physiological function in the heart...

..The mechanism underlying Gd-induced preconditioning appears to be multi-factorial, involving JAK-2, STAT-3 and p44 MAPK pathways, as well as K(ATP) channels...

..Production and metabolism of EETs as well as their specific cellular signaling mechanisms are discussed...

..The role of endothelial nitric oxide synthase (eNOS) in isoflurane postconditioning (IsoPC)-elicited cardioprotection is poorly understood. The authors addressed this issue using eNOS mice...

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..These results suggest that myocardial ischemia and reperfusion decrease cADPR in the myocardium by increasing its hydrolysis. Tissue hypoxia may be one of the important mechanisms to activate cADPR hydrolase...

..Thrombin receptor blockade by PAR4 inhibition provides protection against injury from myocardial I/R by unmasking adenosine receptor signaling and supports the hypothesis of a coupling between thrombin receptors and adenosine receptors...

..Inhibition of NADPH oxidase and K(ATP) channels abolished nitrite-induced cardioprotection. Nitrite but not nitrate protects against infarction by a mechanism involving xanthine oxidoreductase, NADPH oxidase and K(ATP) channels...

..Basic Res Cardiol. 99(1), 29-37]. For the purpose of this review, we will focus primarily on the protective effects of opioids against post-reperfusion myocardial stunning and infarction...

..These data also demonstrate in an in vivo model that IB-MECA is effective as a cardioprotective agent when administered at the time of reperfusion...

..This review aims to highlight some of the research, derived from both the CNS and myocardium, supporting this interesting interaction...

..The potential clinical application and evidence to suggest that opioids produce a similar protective effect in man will also be discussed...

..Furthermore, these data suggest that there are converging pathways and/or receptor cross-talk between A1AR- and DOR-mediated cardioprotection...

..We discuss the possibility that the cardioprotective actions of CPX and BG 9928 may be related to antagonism of A(2B)ARs...

..Dpa confers immediate and sustained cardioprotection in rats, suggesting a potential therapeutic role of this long-acting erythropoietin analog for the treatment of acute myocardial infarction...

..Hence, acute GSK inhibition may provide a novel therapeutic strategy for diabetic patients during an acute myocardial infarction, whereas morphine is less effective due to signaling events that adversely affect GSK3beta...

..These data demonstrate that KOR activation provides a similar degree of infarct size reduction as DOR activation. KOR agonists also reduced arrhythmogenesis; however, these responses appear to be independent of KOR activation...

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..These results suggest that parenteral Cardax may find utility in those clinical applications where pre-treatment of patients at risk for myocardial infarction is performed...

..Understanding the targets of action of EET-mediated protection will promote the development of these fatty acids as therapeutic agents against cardiac ischemia-reperfusion...

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..However, in spite of IPC resistance, hearts can still be pharmacologically protected by direct application of the K(ATP) channel opener bimakalim or the NHE inhibitor EMD 85131...

..These data describe novel findings whereby CM preconditioning is mediated by a PKC-independent pathway involving PKA, beta(2)-AR, and G(s) proteins, whereas AM preconditioning is mediated via G(i) proteins and PKC...

..A better understanding of these relationships will facilitate identification of novel targets for the prevention and/or treatment of ischemic heart disease, a major worldwide public health problem...

..This beneficial effect is mediated by mitochondrial adenosine triphosphate-regulated potassium channels and opioid receptors in vivo...

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..Information gained from these studies will hopefully lead to new therapies to treat patients with ischemic heart disease. ..

..This project is particularly exciting since many opioid agonists are already available to physicians and a long period of drug development may not be necessary before implementing this concept in patients. ..

..The results of these studies will provide exciting new data on the unique role of KATP channels in myocardial ischemia-reperfusion injury...

..They will also determine the role of Ito in cardiac memory. They will use PKC inhibitors, KATP blockers, adenosine antagonists, 4-aminopyridine. ..

..Information gained from these studies will hopefully lead to new therapies to treat patients with ischemic heart disease. ..