A direct role of endogenous prostaglandins in reperfusion-induced cardiac arrhythmias

1989 ◽  
Vol 67 (7) ◽  
pp. 772-779 ◽  
Author(s):  
Margaret P. Moffat ◽  
Gregory R. Ferrier ◽  
Morris Karmazyn
Keyword(s):  
Cardiac Arrhythmias ◽  
Ischemia Reperfusion ◽  
Ischemia And Reperfusion ◽  
Early Repolarization ◽  
Direct Role ◽  
Purkinje Fibres ◽  
Endogenous Prostaglandins ◽  
Pg Release

The possible role of prostaglandins (PG) in arrhythmias associated with ischemia and reperfusion was studied in isolated, superfused canine Purkinje tissues. Ischemic conditions caused partial depolarization and decrease of excitability. Neither inhibition of PG synthesis (ibuprofen, 30 μg/mL) nor addition of exogenous PGF2α (1 ng/mL) modified responses to "ischemia." Reperfusion with normal Tyrode's solution stimulated PG production (measured as 6-keto-PGF1α) and induced a series of electrophysiological events. Under control conditions, Purkinje fibres rapidly repolarized. Subsequently, these tissues began to depolarize and oscillatory afterpotentials appeared. Purkinje tissues depolarized further and became temporarily inexcitable. Return of activity was associated with depolarization-induced automaticity. Ibuprofen prevented reperfusion-stimulated PG release. Ibuprofen also increased the magnitude of early repolarization and greatly attenuated subsequent depolarization. Depolarization-induced automaticity was not observed under these conditions; however, oscillatory afterpotentials were not abolished by ibuprofen. Addition of PGF2α to "ischemic" and reperfusion solutions in the presence of ibuprofen restored the arrhythmogenic responses. We conclude that release of endogenous prostaglandins contributes to electrophysiological changes elicited by reperfusion in canine Purkinje fibres.Key words: arrhythmias, ischemia, reperfusion, ibuprofen, prostaglandins.

The Role of Reactive Oxygen Species, Kinases, Hydrogen Sulfide, and Nitric Oxide in the Regulation of Autophagy and Their Impact on Ischemia and Reperfusion Injury in the Heart

2020 ◽  
Vol 16 ◽  
Author(s):  
Andrey Krylatov ◽  
Leonid Maslov ◽  
Sergey Y. Tsibulnikov ◽  
Nikita Voronkov ◽  
Alla Boshchenko ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Ischemia And Reperfusion ◽  
Oxygen Species ◽  
Ischemia And Reperfusion Injury ◽  
Adaptive Process

: There is considerable evidence in the heart that autophagy in cardiomyocytes is activated by hypoxia/reoxygenation (H/R) or in hearts by ischemia/reperfusion (I/R). Depending upon the experimental model and duration of ischemia, increases in autophagy in this setting maybe beneficial (cardioprotective) or deleterious (exacerbate I/R injury). Aside from the conundrum as to whether or not autophagy is an adaptive process, it is clearly regulated by a number of diverse molecules including reactive oxygen species (ROS), various kinases, hydrogen sulfide (H2S) and nitric oxide (NO). The purpose this review is to address briefly the controversy regarding the role of autophagy in this setting and to examine a variety of disparate molecules that are involved in its regulation.

Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion

2003 ◽  
Vol 284 (1) ◽  
pp. H277-H282 ◽  
Author(s):  
Steven P. Jones ◽  
Michaela R. Hoffmeyer ◽  
Brent R. Sharp ◽  
Ye-Shih Ho ◽  
David J. Lefer
Keyword(s):  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Myocardial Damage ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

Reactive oxygen species induce myocardial damage after ischemia and reperfusion in experimental animal models. Numerous studies have investigated the deleterious effects of ischemia-reperfusion (I/R)-induced oxidant production using various pharmacological interventions. More recently, in vitro studies have incorporated gene-targeted mice to decipher the role of antioxidant enzymes in myocardial reperfusion injury. We examined the role of cellular antioxidant enzymes in the pathogenesis of myocardial I/R (MI/R) injury in vivo in gene-targeted mice. Neither deficiency nor overexpression of Cu-Zn superoxide dismutase (SOD) altered the extent of myocardial necrosis. Overexpression of glutathione peroxidase did not affect the degree of myocardial injury. Conversely, overexpression of manganese (Mn)SOD significantly attenuated myocardial necrosis after MI/R. Transthoracic echocardiography was performed on MnSOD-overexpressing and wild-type mice that were subjected to a more prolonged period of reperfusion. Cardiac output was significantly depressed in the nontransgenic but not the transgenic MnSOD-treated mice. Anterior wall motion was significantly impaired in the nontransgenic mice. These findings demonstrate an important role for MnSOD but not Cu/ZnSOD or glutathione peroxidase in mice after in vivo MI/R.

scholarly journals Tamm-Horsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an MIP-2-dependent mechanism

2011 ◽  
Vol 300 (4) ◽  
pp. F999-F1007 ◽  
Author(s):  
Tarek M. El-Achkar ◽  
Ruth McCracken ◽  
Michael Rauchman ◽  
Monique R. Heitmeier ◽  
Ziyad Al-Aly ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Wild Type Mouse ◽  
Neutrophil Infiltration ◽  
Apical Surface ◽  
Dependent Manner ◽  
Tubular Injury ◽  
Wild Type ◽  
Direct Role

Tamm-Horsfall protein (THP) is a glycoprotein expressed exclusively in thick ascending limbs (TAL) of the kidney. We recently described a novel protective role of THP against acute kidney injury (AKI) via downregulation of inflammation in the outer medulla. Our current study investigates the mechanistic relationships among the status of THP, inflammation, and tubular injury. Using an ischemia-reperfusion model in wild-type and THP−/− mice, we demonstrate that it is the S3 proximal segments but not the THP-deficient TAL that are the main targets of tubular injury during AKI. The injured S3 segments that are surrounded by neutrophils in THP−/− mice have marked overexpression of neutrophil chemoattractant MIP-2 compared with wild-type counterparts. Neutralizing macrophage inflammatory protein-2 (MIP-2) antibody rescues S3 segments from injury, decreases neutrophil infiltration, and improves kidney function in THP−/− mice. Furthermore, using immunofluorescence volumetric imaging of wild-type mouse kidneys, we show that ischemia alters the intracellular translocation of THP in the TAL cells by partially shifting it from its default apical surface domain to the basolateral domain, the latter being contiguous to the basolateral surface of S3 segments. Concomitant with this is the upregulation, in the basolateral surface of S3 segments, of the scavenger receptor SRB-1, a putative receptor for THP. We conclude that TAL affects the susceptibility of S3 segments to injury at least in part by regulating MIP-2 expression in a THP-dependent manner. Our findings raise the interesting possibility of a direct role of basolaterally released THP on regulating inflammation in S3 segments.

scholarly journals Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edema

2009 ◽  
Vol 297 (1) ◽  
pp. L52-L63 ◽  
Author(s):  
Giorgio Zanotti ◽  
Monica Casiraghi ◽  
John B. Abano ◽  
Jason R. Tatreau ◽  
Mayura Sevala ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Ischemia And Reperfusion ◽  
Endothelial Monolayers ◽  
Microvascular Endothelial ◽  
Parenchymal Cells ◽  
Deficient Mice

Toll-like receptors (TLRs) of the innate immune system contribute to noninfectious inflammatory processes. We employed a murine model of hilar clamping (1 h) with reperfusion times between 15 min and 3 h in TLR4-sufficient (C3H/OuJ) and TLR4-deficient (C3H/HeJ) anesthetized mice with additional studies in chimeric and myeloid differentiation factor 88 (MyD88)- and TLR4-deficient mice to determine the role of TLR4 in lung ischemia-reperfusion injury. Human pulmonary microvascular endothelial monolayers were subjected to simulated warm ischemia and reperfusion with and without CRX-526, a competitive TLR4 inhibitor. Functional TLR4 solely on pulmonary parenchymal cells, not bone marrow-derived cells, mediates early lung edema following ischemia-reperfusion independent of MyD88. Activation of MAPKs and NF-κB was significantly blunted and/or delayed in lungs of TLR4-deficient mice as a consequence of ischemia-reperfusion injury, but edema development appeared to be independent of activation of these signaling pathways. Pretreatment with a competitive TLR4 inhibitor prevented edema in vivo and reduced actin cytoskeletal rearrangement and gap formation in pulmonary microvascular endothelial monolayers subjected to simulated warm ischemia and reperfusion. In addition to its well-accepted role to alter gene transcription, functioning TLR4 on pulmonary parenchymal cells plays a key role in very early and profound pulmonary edema in murine lung ischemia-reperfusion injury. This may be due to a novel mechanism: regulation of endothelial cell cytoskeleton affecting microvascular endothelial cell permeability.

Abstract 341: GsMTx4-D is a Cardioprotectant against Myocardial Infarction during Ischemia and Reperfusion

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ji Li ◽  
Jinli Wang ◽  
Frederick Sachs ◽  
Thomas M Suchyna
Keyword(s):  
Cardiac Output ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mouse Heart ◽  
Ischemia And Reperfusion ◽  
Ischemic Reperfusion Injury ◽  
Multiple Systems ◽  
Ischemic Reperfusion ◽  
Infarct Area

Rationale: GsMTx4 peptide is a selective inhibitor of cation selective mechanosensitive ion channels (MSCs) and has helped establish the role of MSCs in cardiac physiology. However, the role of MSCs in ischemic reperfusion injury was unknown. Cation imbalance appears to be a major contributor to ischemic reperfusion injury across multiple systems. MSCs may be significant contributors to the cation overload, and they are likely to be activated in reperfusion due to inhomogeneous local stresses and compromised mechanical support of the sarcolemma. Objective: The aim of this study was to determine if the D enantiomer of GsMTx4 can act as a cardioprotectant during ischemia/reperfusion in mice. Methods and Results: GsMTx4-D pharmacokinetics in the plasma and heart was monitored over 24 hrs using an LCMSMS assay. Ischemia and reperfusion in the mouse heart involved ligating a coronary artery for 20 min followed by release of the ligature. GsMTx4-D was administered by either acute intravenous injection during the ischemic event, or a day prior to the event with two days of intraperitoneal injections, once per day. Dosing of GsMTx4-D was adjusted to achieve tissue concentrations of 1-5 μM. Relative to vehicle injected animals, GsMTx4-D reduced infarct area by >40% for both acute and pretreated animals. Cardiac output was indistinguishable between sham-treated control hearts and GsMTx4-D pretreatment, and arrhythmias were also significantly reduced by intravenous injections of GsMTx4-D. Conclusions: GsMTx4-D is a potent cardioprotectant that decreases infarct area, increases cardiac output and decreases arrhythmias that are caused by ischemia and reperfusion. GsMTx4-D was not toxic and promises to be a useful therapy in reperfusion of the heart and other organs.

scholarly journals Prevention of bacterial translocation using beta-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

2006 ◽  
Vol 21 (suppl 4) ◽  
pp. 18-22 ◽  
Author(s):  
Irami Araújo-Filho ◽  
Amália Cínthia Meneses Rêgo ◽  
Laíza Araújo Mohana Pinheiro ◽  
Italo Medeiros Azevedo ◽  
Vítor Brasil Medeiros ◽  
...  
Keyword(s):  
Small Bowel ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Bowel Ischemia ◽  
Ischemia And Reperfusion ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Group I ◽  
Colony Forming Units

PURPOSE: To investigate the role of beta-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. METHODS: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFalpha, IL-1beta, IL-6, IL-10 were measured by ELISA. RESULTS: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFalpha, IL-1beta and, IL-6, compared to I/R untreated animals. CONCLUSION: The beta-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria.

1843: Role of Cxcr2 in Renal Ischemia/Reperfusion Injury

2004 ◽  
Vol 171 (4S) ◽  
pp. 487-487
Author(s):  
Motoo Araki ◽  
Masayoshi Miura ◽  
Hiromi Kumon ◽  
John Belperio ◽  
Robert Strieter ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury
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