title: Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion.
abstract: The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in rabbits. No-reflow was not dependent on the reduction of infarct size.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Binzhou Medical University, China.
authors.forename: X J
authors.initials: XJ
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Qilu Hospital, Shandong University, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University, China.
authors.forename: G X
authors.initials: GX
authors.lastname: He
authors.affiliation: Department of Cardiology, Affiliated Hospital of Binzhou Medical University, China.
authors.forename: H P
authors.initials: HP
authors.lastname: Xu
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D054059:Coronary Occlusion / Q000188:drug therapy; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006538:Heptanoic Acids / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008026:Ligation; D008297:Male; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D054318:No-Reflow Phenomenon / Q000188:drug therapy* / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage*; D011817:Rabbits; D011897:Random Allocation
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D015850:Interleukin-6; D011758:Pyrroles; D007371:Interferon-gamma; D000069059:Atorvastatin