Biomedical subjects

Zequan Yang

Publications and source records attributed to Zequan Yang.

21 records · Page 2Linked to original sources

PubMed2002

Left ventricular remodeling subsequent to reperfused myocardial infarction: evaluation of a rat model using cardiac magnetic resonance imaging.

PURPOSE: This study characterized the time course of ventricular remodeling subsequent to reperfused myocardial infarction (MI) in a rat model using cardiac magnetic resonance (MR) imaging. METHODS AND RESULTS: Short axis cine MR imaging was used to measure left ventricular ejection fraction (LVEF) and left ventricular volumes in Lewis rats at baseline, 1, 2, 4, 6, 8, and 10 weeks post-MI. Ventricular pressure and myocardial mass were evaluated at the 10 week time point. RESULTS: Measurements of LVEF showed a significant decrease in cardiac function immediately after MI with no significant changes over the remainder of the time course. Measurements of left ventricular end-systolic volume (LVESV) showed significant increases over thefirst 4 weeks after MI with no significant changes over the remainder of the time course. Statistical analysis of the MR measurements of LVESV yielded a repeatability standard error of 3.3%, an inter-observer standard error of 3.3%, and an intra-observer standard error of 1.6%. CONCLUSION: This study indicates that cine MRI can be used to longitudinally evaluate changes in ventricular structure and function in a rat model of left ventricular remodeling. In this animal model, preliminary results indicate that the majority of remodeling is completed by 4 weeks and no significant changes in LVEF are seen after the first week. The repeatability values indicate that cardiac MR could be used for evaluating new therapies for mitigating the effects of LV remodeling after reperfused MI.

Animals↗

PubMed2002

Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-kappaB and AP-1 activation and enhances myocardial damage.

The role of nitric oxide (NO) generated by the inducible NO synthase (iNOS) during myocardial ischemia and reperfusion is not understood. We investigated the role of iNOS during early reperfusion damage induced in genetically deficient iNOS (iNOS-/-) mice and wild-type littermates. In wild-type mice, ischemia (60 min) and reperfusion (60 min) induced an elevation in serum levels of creatine phosphokinase and myocardial injury characterized by the presence of scattered apoptotic myocytes and mild neutrophil infiltration. Northern blot analysis showed increased expression of iNOS, whose activity was markedly elevated after reperfusion. Immunohistochemistry showed staining for nitrotyrosine; Western blot analysis showed elevated expression of heat shock protein 70 (HSP70), a putative cardioprotective mediator. Plasma levels of nitrite and nitrate, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-10 were also increased. These events were preceded by degradation of inhibitor kappaBalpha (IkappaBalpha), activation of IkappaB kinase complex (IKK) and c-Jun-NH2-terminal kinase (JNK), and subsequently activation of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) as early as 15 min after reperfusion. In contrast, iNOS-/- mice experienced 35% mortality after reperfusion. The extensive myocardial injury was associated with marked apoptosis and infiltration of neutrophils whereas expression of HSP70 was less pronounced. Nitrotyrosine formation and plasma levels of nitrite and nitrate were undetectable. TNF-alpha and IL-6 were increased and IL-10 was reduced in earlier stages of reperfusion. Activation of IKK and JNK and binding activity of NF-kappaB and AP-1 were significantly reduced. Thus, we conclude that iNOS plays a beneficial role in modulating the early defensive inflammatory response against reperfusion injury through regulation of signal transduction.

Animals↗

PubMed2002

Cardiac overexpression of A1-adenosine receptor protects intact mice against myocardial infarction.

Previous studies have shown that high-level (300-fold normal) cardiac overexpression of A1-adenosine receptors (A1-ARs) in transgenic (TG) mice protects isolated hearts against ischemia-reperfusion injury. However, this high level of overexpression is associated with bradycardia and increased incidence of arrhythmia during ischemia in intact mice, which interfered with studies to determine whether this line of TG mice might also be protected against myocardial infarction (MI) in vivo. For these studies, we therefore selected a line of TG mice that overexpresses the A1-AR at more moderate levels (30-fold normal), which affords cardioprotection in the isolated heart while minimizing bradycardia and arrhythmia during ischemia in intact mice. Wild-type (WT; n = 10) and moderate-level A1-AR TG (n = 10) mice underwent 45 min of left anterior descending coronary artery occlusion, followed by 24-h reperfusion. Infarct size and region at risk were determined by triphenyltetrazolium chloride and phthalo blue staining, respectively. Infarct size (% region at risk) in WT mice was 52 +/- 3%, whereas overexpression of A1-ARs in the TG mice markedly reduced infarct size to 31 +/- 3% (P < 0.05). Furthermore, contractile function (left ventricular ejection fraction) as determined by cardiac magnetic resonance imaging 24 h after MI was better preserved in TG vs. WT mice. Cardiac overexpression of A1-ARs reduces infarct size by 40% and preserves cardiac function in intact mice after MI.

Animals↗