scholarly journals Disruption of Nox2 and TNFRp55/p75 eliminates cardioprotection induced by anisomycin

2012 ◽  
Vol 303 (10) ◽  
pp. H1263-H1272 ◽  
Author(s):  
Ting C. Zhao ◽  
Ling Zhang ◽  
Jun T. Liu ◽  
Tai L. Guo
Keyword(s):  
Infarct Size ◽  
Myocardial Injury ◽  
Left Ventricular ◽  
Kinase Assay ◽  
Protective Effects ◽  
Perfused Heart ◽  
Transient Activation ◽  
Novel Approach ◽  
Tnf Α ◽  
A Subunit

Transient activation of p38 through anisomycin is demonstrated to precondition the heart against myocardial injury. However, it remains unknown whether specific TNF-α receptor (TNFR) p55/p75 and Nox2, a subunit of NADPH oxidase, are involved in this event. We sought to investigate whether the genetic disruption of TNFRp55/p75 and Nox2 eliminated cardioprotection elicited by anisomycin and whether p38-dependent activation of Nox2 stimulated TNFR to ultimately achieve protective effects. Adult wild-type and TNFR p55/p75−/−and Nox2−/−mice received intraperitoneal injections of anisomycin (0.1 mg/kg), a potent activator of p38. The hearts were subjected to 30 min myocardial ischemia/30 min reperfusion in the Langendorff perfused heart after 24 h. Left ventricular function was measured, and infarct size was determined. Myocardial TNF-α protein, Nox2, and superoxides releases were detected. Gel kinase assay was employed to detect the effect of p38 on Nox2 phosphorylation. Activation of p38 through anisomycin produces marked improvements in left ventricular functional recovery, and the reduction of myocardial infarction, which were abrogated by disruption of Nox2 and TNFR p55/p75. Disruption of Nox2 and TNFR p55/p75 abolished the effect of anisomycin-induced reduction of infarct size. Anisomycin induced the production of TNF-α, which was abrogated in Nox2−/−mice and by treatment with SB203580, but not by disruption of p55/p75. Anisomycin treatment resulted in an increase in Nox2 protein and the phosphorylation of Nox2, which was blocked by inhibition of p38. Taken together, these results indicate that stimulation of the Nox2 and TNFR p55/p75 pathway is a novel approach to anisomycin-induced cardioprotection.

Abstract 146: Disruption of Nox2 and TNFRp55/p75 Eliminates Anisomycin-Induced Preconditioning Effect in the Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ting C Zhao ◽  
Ling Zhang ◽  
Tai-Liang Guo
Keyword(s):  
Infarct Size ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Kinase Assay ◽  
Protective Effects ◽  
Triphenyltetrazolium Chloride ◽  
Transient Activation ◽  
Novel Approach ◽  
Tnf Α ◽  
A Subunit

Background: Transient activation of p38 through anisomycin is demonstrated to precondition the heart against myocardial injury. However, it remains unknown whether specific TNF-α receptor (TNFR) p55/p75 and Nox2, a subunit of NADPH-oxidase are involved in this event. Objective: We sought to investigate whether the genetic disruption of TNFRp55/p75 and Nox2 eliminates cardioprotection elicited by anisomycin and whether p38-dependent activation of Nox2 stimulates TNFR to ultimately achieve protective effects. Methods: Adult wild type and p55/p75 -/- and Nox2 -/- mice received intraperitoneal injections of anisomycin (0.1mg/kg), a potent activator of p38. The hearts were subjected to 30 min myocardial ischemia /30 min reperfusion in the Langendorff perused heart after twenty four hours. Left ventricular function was measured and infarct size was determined by triphenyltetrazolium chloride. Myocardial TNF-α protein, Nox2 and superoxides releases were detected. Gel kinase assay was employed to detect the effect of p38 on Nox2 phosphorylation. Results: Activation of p38 through anisomycin produces marked improvements in the recovery of left ventricular end diastolic pressure, rate pressure products, and the reduction of myocardial infarction, which were completely abrogated by disruption of Nox2 and TNFR p55/p75. Genetic disruption of Nox2 and TNFR p55/p75 abolished the effect of anisomycin-induced reduction of infarct size. Ansiomycin induced the production of TNFα, which was abrogated in Nox2 -/- mice. Notably, activation of p38 resulted in the phosphorylation of Nox2. Conclusion: Taken together, these results indicate that stimulation of the Nox2 and TNFR p55/p75 pathway is a novel approach to anisomycin-induced cardioprotection.

scholarly journals pGlu-serpinin protects the normotensive and hypertensive heart from ischemic injury

2015 ◽  
Vol 227 (3) ◽  
pp. 167-178 ◽  
Author(s):  
T Pasqua ◽  
B Tota ◽  
C Penna ◽  
A Corti ◽  
M C Cerra ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Chromogranin A ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Protective Effects ◽  
Perfused Heart ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Serpinin peptides derive from proteolytic cleavage of Chromogranin-A at C-terminus. Serpinin and the more potent pyroglutaminated-serpinin (pGlu-Serp) are positive cardiac β-adrenergic-like modulators, acting through β1-AR/AC/cAMP/PKA pathway. Because in some conditions this pathway and/or other pro-survival pathways, activated by other Chromogranin-A fragments, may cross-talk and may be protective, here we explored whether pGlu-Serp cardioprotects against ischemia/reperfusion injury under normotensive and hypertensive conditions. In the latter condition, cardioprotection is often blunted because of the limitations on pro-survival Reperfusion Injury Salvage Kinases (RISK) pathway activation. The effects of pGlu-Serp were evaluated on infarct size (IS) and cardiac function by using the isolated and Langendorff perfused heart of normotensive (Wistar Kyoto, WKY) and spontaneously hypertensive (SHR) rats exposed to ischemic pre-conditioning (PreC) and post-conditioning (PostC). In both WKY and SHR rat, pGlu-Serp induced mild cardioprotection in both PreC and PostC. pGlu-Serp administered at the reperfusion (Serp-PostC) significantly reduced IS, being more protective in SHR than in WKY. Conversely, left ventricular developed pressure (LVDevP) post-ischemic recovery was greater in WKY than in SHR. pGlu-Serp-PostC reduced contracture in both strains. Co-infusion with specific RISK inhibitors (PI3K/Akt, MitoKATP channels and PKC) blocked the pGlu-Serp-PostC protective effects. To show direct effect on cardiomyocytes, we pre-treated H9c2 cells with pGlu-Serp, which were thus protected against hypoxia/reoxygenation. These results suggest pGlu-Serp as a potential modulatory agent implicated in the protective processes that can limit infarct size and overcome the hypertension-induced failure of PostC.

scholarly journals Cardioprotective effects of Ginsenoside compound-Mc1 and Dendrobium Nobile Lindl against myocardial infarction in an aged rat model: Involvement of TLR4/NF-κB signaling pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Yongle Sun ◽  
Jing Geng ◽  
Deyu Wang
Keyword(s):  
Myocardial Infarction ◽  
Combination Therapy ◽  
Infarct Size ◽  
Signaling Pathway ◽  
Left Ventricular ◽  
Male Rats ◽  
Dendrobium Nobile ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Dendrobium Nobile Lindl

Aging is the crucial co-morbidity that prevents the full cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Combination therapy as a promising strategy may overcome this clinical problem. This study aimed to investigate the cardioprotective effects of Ginsenoside compound-Mc1 (GMc1) and Dendrobium Nobile Lindl (DNL) in myocardial I/R injury and explore the involvement of the TLR4/NF-κB signaling pathway in aged rats. In vivo I/R injury and myocardial infarction was established by temporary coronary ligation in 22–24 months’ old Sprague Dawley male rats. GMc1 (10 mg/kg) and DNL (80 mg/kg) were administered intraperitoneally for 4 weeks and orally for 14 days, respectively, before I/R injury. Infarct size was measured through triphenyl-tetrazolium-chloride staining. ELISA assay was conducted to quantify the levels of cardiotroponin, and myocardial content of TNF-α and glutathione. Western blotting was employed to detect the expression of TLR4/MyD88/NF-κB proteins. GMc1 and DNL significantly reduced the infarct size to a similar extent ( p < 0.05) but their combined effect was greater than individual ones ( p < 0.01). Combination therapy significantly restored the left ventricular end-diastolic and developed pressures at the end of reperfusion as compared with the untreated group ( p < 0.01). Although the GMc1 and DNL reduced the levels of inflammatory cytokine TNF-α and increased the contents of antioxidant glutathione significantly, their individual effects on the reduction of protein expression of TLR4/MyD88/NF-κB pathway were not consistent. However, their combination could significantly reduce all parameters of this inflammatory pathway as compared to untreated I/R rats ( p < 0.001). Therefore, the combined treatment with GMc1 and DNL increased the potency of each intervention in protecting the aged hearts against I/R injury. Reduction in the activity of the TLR4/MyD88/NF-κB signaling pathway and subsequent modulation of the activity of inflammatory cytokines and endogenous antioxidants play an important role in this cardioprotection.

Abstract P293: Endogenous Lats2 Plays an Important Role in Mediating Myocardial Injury Caused by Ischemia/Reperfusion Through Inhibition of FoxO3

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Dan Shao ◽  
Peiyong Zhai ◽  
Junichi Sadoshima
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Area At Risk ◽  
Perfused Heart ◽  
Developed Pressure

Lats2 is a tumor suppressor and a serine/threonine kinase, acting downstream of mammalian sterile 20 like kinase1 (Mst1), which stimulates apoptosis and inhibits hypertrophy in cardiomyocytes (CM). We investigated the role of Lats2 in mediating myocardial injury after ischemia/reperfusion (IR). Phosphorylation of YAP, an in vivo substrate of Lats2, was increased after 45 minutes ischemia followed by 24 hours reperfusion in control mouse hearts compared with sham, but not in dominant negative (DN) Lats2 transgenic mouse (Tg) hearts, suggesting that Lats2 is activated by IR. The size of myocardial infarction (MI)/area at risk was significantly smaller in Tg mice than in NTg mice (19% and 49%, p<0.01). And there were fewer TUNEL positive cells in Tg than in NTg mice (0.04% and 0.11%, p<0.05). Following 30 min of global ischemia and 60 min of reperfusion in Langendorff perfused heart preparations, left ventricular (LV) systolic pressure (100 vs 71mmHg, p<0.05) and LV developed pressure (79 vs 47 mmHg, p<0.05) were significantly greater in Tg than in NTg mice, indicating that suppression of Lats2 induces better functional recovery after IR. Oxidative stress, as evaluated by 8-OHdG staining, was attenuated in Tg mice. In cultured CMs, DN-Lats2 significantly decreased H 2 O 2 -induced cell death. Overexpression of Lats2 significantly downregulated (51% and 75%, p<0.05), whereas that of DN-Last2 upregulated (100 and 70%, p<0.05), MnSOD and catalase, suggesting that Lats2 negatively regulates expression of antioxidants. Reporter gene assays showed that overexpression of Lats2 significantly inhibits (−70%), whereas knocking down Lats2 by sh-Lats2 increases (+60%), FoxO3-mediated transcriptional activity. Overexpression of Lats2 in CMs inhibited FoxO3 expression, whereas that of DN-Lats2 significantly inhibited FoxO3 downregulation after IR in vivo, suggesting that Lats2 negatively regulates FoxO3 protein expression, which may lead to the downregulation of MnSOD and catalase. Taken together, these results suggest that endogenous Lats2 plays an important role in mediating myocardial injury in response to IR, In part through downregulation of FoxO3 and consequent downregulation of antioxidants and increased oxidative stress in the heart.

scholarly journals Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

2018 ◽  
Vol 45 (5) ◽  
pp. 1797-1806 ◽  
Author(s):  
Anbang Han ◽  
Yingdong Lu ◽  
Qi Zheng ◽  
Jian Zhang ◽  
YiZhou Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathways ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Protective Effects ◽  
Tnf Α ◽  
Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

Isoflurane-induced preconditioning is attenuated by diabetes

2002 ◽  
Vol 282 (6) ◽  
pp. H2018-H2023 ◽  
Author(s):  
Katsuya Tanaka ◽  
Franz Kehl ◽  
Weidong Gu ◽  
John G. Krolikowski ◽  
Paul S. Pagel ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Area At Risk ◽  
End Tidal

Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated K+ channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 ± 3% ( n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 ± 2 and 13 ± 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 ± 3%; n = 8) but blocked the protective effects of 0.32% (27 ± 2%; n = 7) and not 0.64% isoflurane (18 ± 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning.

Astragaloside attenuates cardiotoxicity effects of Doxorubicin by inhibiting TLR4/NF-кB signaling pathway

2017 ◽  
Vol 5 (1) ◽  
pp. 93-108
Author(s):  
Russell Nahorski ◽  
Arnim Ploeger
Keyword(s):  
Protein Expression ◽  
Treated Group ◽  
Left Ventricular ◽  
Lv Function ◽  
Total Protein Content ◽  
Limiting Factor ◽  
Transverse Diameter ◽  
Protective Effects ◽  
Tlr4 Mrna ◽  
Tnf Α

Doxorubicin (DOX) is one of the most widely used and successful antitumor drugs, but its cumulative and dose-dependent cardiac toxicity has been the major concern of oncologists in cancer therapeutic practice for decades. Cardiotoxicity is a major limiting factor in anticancer therapy. Astragaloside (Ast) is one of the main effective components isolated from the traditional Chinese medical herb Astragalus membranaceus. The possible protective effects Ast against cardiotoxicity were investigated in wild type C57BL/6 mice treated with saline, saline+doxorubicin (DOX; 20 mg/kg) or Ast (20 mg/kg)+DOX continued for a period of 5 weeks. The cardiomyopathy was assessed using transthoracic echocardiography before the start of treatment and after 14 days and plasma lactate dehydrogenase (LDH) activity was measured after 14 days. Cardiac catheterizations for assessments LV function before the mice were decapitated. To measure the transverse diameter of left ventricular myocardial cells (TDM), the hematoxylin-eosin (HE) staining method was applied. In addition, the volume and the total protein content of cardiomyocytes were measured, the mRNA expression of ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4, IκBα and p65 were quantified by Western blot, and the level of TNF-α and IL-6 were measured by ELISA. Ast treatment demonstrated improved LV function, TDM were significantly decreased; the protein expression of TLR4 and p65 were reduced, while the IκBα were increased; the expression of ANP, TLR4 mRNA, and TNF-α, IL-6 in serum were significantly reduced compared with the doxorubicin-treated group. The study suggests that Ast may have a potential protective role against doxorubicin-induced cardiotoxicity in mice.

scholarly journals Evidence for a role of opioids in epoxyeicosatrienoic acid-induced cardioprotection in rat hearts

2010 ◽  
Vol 298 (6) ◽  
pp. H2201-H2207 ◽  
Author(s):  
Garrett J. Gross ◽  
John E. Baker ◽  
Anna Hsu ◽  
Hsiang-en Wu ◽  
John R. Falck ◽  
...  
Keyword(s):  
Infarct Size ◽  
Pertussis Toxin ◽  
Isolated Heart ◽  
Myocardial Infarct ◽  
Antinociceptive Effect ◽  
Left Ventricular ◽  
Endogenous Opioids ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Area At Risk

We previously demonstrated that several epoxyeicosatrienoic acids (EETs) produce reductions in myocardial infarct size in rats and dogs. Since a recent study demonstrated the release of opioids in mediating the antinociceptive effect of 14,15-EET, we hypothesized that endogenous opioids may also be involved in mediating the cardioprotective effect of the EETs. To test this hypothesis, we used an in vivo rat model of infarction and a rat Langendorff model. In the infarct model, hearts were subjected to 30 min occlusion of the left coronary artery and 2 h reperfusion. Animals were treated with 11,12-EET or 14,15-EET (2.5 mg/kg) alone 15 min before occlusion or with opioid antagonists [naloxone, naltrindole, nor-binaltorphimine (nor-BNI), and d-Phe-Cys-Tyr-d-Trp-Om-Thr-Pen-Thr-NH2 (CTOP), a nonselective, a selective δ, a selective κ, and a selective μ receptor antagonist, respectively] 10 min before EET administration. In four separate groups, antiserum to Met- and Leu-enkephalin and dynorphin-A-(1–17) was administered 50 min before the 11,12-EET administration. Infarct size expressed as a percent of the area at risk (IS/AAR) was 63.5 ± 1.2, 45.3 ± 1.0, and 40.9 ± 1.2% for control, 11,12-EET, and 14,15-EET, respectively. The protective effects of 11,12-EET were abolished by pretreatment with either naloxone (60.5 ± 1.8%), naltrindole (60.8 ± 1.0%), nor-BNI (62.3 ± 2.8%), or Met-enkephalin antiserum (63.2 ± 1.7%) but not CTOP (42.0 ± 3.0%). In isolated heart experiments, 11,12-EET was administered to the perfusate 15 min before 20 min global ischemia followed by 45 min reperfusion in control hearts or in those pretreated with pertussis toxin (48 h). 11,12-EET increased the recovery of left ventricular developed pressure from 33 ± 1 to 45 ± 6% ( P < 0.05) and reduced IS/AAR from 37 ± 4 to 20 ± 3% ( P < 0.05). Both pertussis toxin and naloxone abolished these beneficial effects of 11,12-EET. Taken together, these results suggest that the major cardioprotective effects of the EETs depend on activation of a Gi/o protein-coupled δ- and/or κ-opioid receptor.

Hyperthermia-Induced Cardioprotection Is Potentiated by Ischemic Postconditioning in Rats

2009 ◽  
Vol 234 (5) ◽  
pp. 573-581 ◽  
Author(s):  
Yukichi Murozono ◽  
Naohiko Takahashi ◽  
Tetsuji Shinohara ◽  
Tatsuhiko Ooie ◽  
Yasushi Teshima ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Ischemic Postconditioning ◽  
Initial Moment ◽  
Protective Effects ◽  
Perfused Heart ◽  
Ventricular Performance ◽  
Akt Phosphorylation

We tested the hypothesis that the protective effects of hyperthermia (HT) could be augmented by ischemic postconditioning (PostC) via enhancement of reperfusion-induced Akt phosphorylation. The role of the mitoKATP channel as an effecter to protect hearts against ischemia/reperfusion injury was also investigated. In isolated perfused heart experiments using a Langendorff apparatus, 30 min of no-flow global ischemia was followed by 120 min of reperfusion. Ischemic PostC, 5 cycles of 10-sec reperfusion/10-sec ischemia, was achieved at the initial moment of reperfusion. Hyperthermia (HT, 43°C for 20 min) was applied 24 hr before ischemia onset. Ischemic PostC alone did not show significant protection, but HT did. The HT-induced protection in terms of infarct size, recovery of left ventricular performance, amount of released creatine kinase and apoptosis were enhanced by ischemic PostC. These protective effects were consistent with the levels of Akt phosphorylation 7 min after reperfusion and were completely blocked by the pretreatment with the phosphatidylinositol 3-kinase inhibitor wortmannin. HT-induced protection was also completely abolished by concomitant perfusion with 5-hydroxydecanoate (5HD, 100 μM), an inhibitor of the mitochondrial ATP-sensitive potassium (mitoKATP) channel. However, the potentiated protection by ischemic PostC remained, even in the presence of 5HD. In conclusion, ischemic PostC could potentiate the protective effects of HT possibly via enhancement of reperfusion-induced Akt phosphorylation. Although the opening of the mitoKATP channel is predominantly involved as an effecter in HT-induced protection, potentiated protection by ischemic PostC may involve mechanisms other than the mitoKATP channel.

Nicorandil reduces myocardial injury and improves cardiac function in valve replacement surgery.

2019 ◽  
Vol 1 (4) ◽  
pp. 120-126
Author(s):  
Wael Elfeky ◽  
Mohamed Aboelnasr ◽  
Ayman Sallam ◽  
Wael Haseeb ◽  
Dalia R El-Afify
Keyword(s):  
Valve Replacement ◽  
Myocardial Protection ◽  
Myocardial Injury ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Replacement Surgery ◽  
Tnf Α ◽  
Valve Replacement Surgery

Background: Myocardial injury during cardiac surgery is associated with increased morbidity and mortality, and proper myocardial protection improves surgical outcomes. We aimed to study the role of preoperative nicorandil in myocardial protection during valve replacement surgery. Methods: The study included 40 patients who were randomized into two groups: control group, and nicorandil group. Preoperative, intraoperative, and postoperative data were collected. Creatine kinase- MB (CK-MB), troponin I, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured 24-hours before surgery then 4, 12 and 48 hours after aortic cross-clamp removal. Results: Nicorandil significantly decreased MDA (p=0.005 and 0.036), TNF-α (p< 0.001), IL-6 (p<0.001 and 0.003) 4 and 12 hours following the removal of aortic clamp compared to the control group. Additionally, It significantly reduced CK-MB (p< 0.0001 and 0.0002) and troponin-I (p= 0.0002 and < 0.0001) 4 and 12 hours after the removal of the aortic clamp, respectively. However, there was no significant difference in MDA, TNF-α, IL-6, CK-MB, and troponin-I levels between the nicorandil and the control group after 48 hours following the removal of aortic clamping (p= 0.084; 0.64; 0.12; 0.12; 0.75; respectively). Conclusions: Nicorandil reduced myocardial injury significantly in valve replacement surgery. Nicorandil decreased CK-MB and troponin I and improved postoperative left ventricular ejection fraction.

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