High dose aspirin and left ventricular remodeling after myocardial infarction: aspirin and myocardial infarction.
Journal - Basic research in cardiology (Germany )
BACKGROUND: Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. METHODS AND RESULTS: Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 +/- 1.7 vs. placebo MI 15.9 +/- 2.5 mm(2)), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 +/- 1.3 mm(2), p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1beta were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. CONCLUSION: Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function.
|ISSN : ||0300-8428|
|Mesh Heading : ||Animals Anti-Inflammatory Agents, Non-Steroidal Aspirin Collagen Coronary Vessels Disease Models, Animal Dose-Response Relationship, Drug Female Infusion Pumps, Implantable Interleukin-1beta Ligation Mice Mice, Inbred C57BL Myocardial Infarction Myocardium Organ Size Time Factors Tumor Necrosis Factor-alpha Ventricular Function, Left Ventricular Pressure Ventricular Remodeling administration & dosage therapeutic use administration & dosage therapeutic use metabolism surgery metabolism metabolism pathology physiopathology metabolism drug effects metabolism drug effects|
|Mesh Heading Relevant : ||pharmacology pharmacology drug therapy drug effects drug effects|
Role of 5-lipoxygenase in myocardial ischemia-reperfusion injury in mice.
Journal - European journal of pharmacology (Netherlands )
Myocardial ischemia induces 5-lipoxygenase (LOX) translocation and leukotriene production in the heart. Leukotrienes increase inflammatory responses and could thereby aggravate ischemic injury. However, the role of lipoxygenase and leukotrienes in cardiac ischemia/reperfusion damage has not been well defined. Therefore, we tested the effect of ischemia reperfusion in mice with targeted deletion of 5-lipoxygenase, the enzyme converting arachidonic acid in leukotrienes. 5-LOX deficient (KO) and wild-type (WT) mice underwent 30 min of coronary artery ligation and 24 h of reperfusion in vivo. In mice with equivalent area at risk, infarct size was not significantly different between WT and KO mice (infarct/area at risk 61.7+/-3.9 vs. 55.8+/-6.6%, WT vs. KO, P=n.s.). However, neutrophil infiltration as well as tumor necrosis factor expression were increased in 5-lipoxygenase deficient mice. In summary, inhibition of 5-lipoxygenase does not affect cardiac ischemia-reperfusion injury but the post-ischemic inflammatory response.
|ISSN : ||0014-2999|
|Mesh Heading : ||Animals Arachidonate 5-Lipoxygenase Gene Expression Immunohistochemistry Leukotrienes Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction Myocardial Reperfusion Injury Myocardium Neutrophil Infiltration RNA Risk Factors Tumor Necrosis Factor-alpha genetics pathology pathology metabolism pathology genetics metabolism genetics metabolism|
|Mesh Heading Relevant : ||metabolism metabolism metabolism metabolism|
Tissue-Specific Effects of the Nuclear Factor ?B Subunit p50 on Myocardial Ischemia-Reperfusion Injury
Journal - The American Journal of Pathology
Nuclear factor ?B (NF-?B) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-?B in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-?B subunit p50. Electrophoretic mobility shift assays validated NF-?B activation in wild-type (WT) but not p50 knockout (KO) mice. KO and WT animals underwent 30 minutes of coronary artery ligation and 24 hours of reperfusion in vivo. Ischemia-reperfusion damage was significantly reduced in the p50 KO when compared with matching WT mice. Although adhesion molecules such as intercellular adhesion molecule were up-regulated in left ventricles of p50 KO animals, fewer neutrophils infiltrated the infarct area, suggesting leukocytes as a potential mediator of the protection observed in the p50 KO. This was confirmed in adoptive transfer experiments: whereas transplantation of KO bone marrow in KO animals sustained the protective effect on ischemia-reperfusion injury, transplantation of WT bone marrow in KO animals abolished it. Thus, deletion of the NF-?B subunit p50 reduces ischemia-reperfusion injury in vivo, associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-?B activation in p50 KO leukocytes attenuates cardiac damage.