ABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of pravastatin on myocardial connexin 43 (Cx43), IFN-gamma and IL-10 expressions in a murine model of viral myocarditis (VMC) induced by Coxsackievirus B3.</p><p><b>METHODS</b>Four-week-old male Balb/c mice were inoculated intraperitoneally with Coxsackievirus B3 and then randomly received saline (group A, n = 12), low dose pravastatin (40 mg.kg(-1).d(-1), group B, n = 12) and high dose pravastatin (80 mg.kg(-1).d(-1), group C, n = 12) for 14 days. Another group of mice were injected with Eagle's solution and treated with saline (group D, n = 12) or high dose pravastatin (80 mg.kg(-1).d(-1), group E, n = 12). After 14 days treatments, serum IFN-gamma, IL-10 were assayed using ELISA, myocardium IFN-gamma, IL-10 and Cx43 mRNA levels were measured by real-time PCR, myocardium expression of Cx43 was also determined by immunohistochemistry staining method on cardiac myocytes.</p><p><b>RESULTS</b>Pravastatin dose-dependently upregulated Cx43 proteins on membrane of myocardial cells (group A: 0.16 +/- 0.06, group B: 4.55 +/- 0.73 and group C: 5.21 +/- 0.42, P < 0.01 vs. group A) and Cx43 mRNA expression (group A: 1.000 +/- 0.127, group B: 1.320 +/- 0.096, group C: 1.550 +/- 0.126, P < 0.05 vs. group A), IL-10 mRNA expression (group A: 1.000 +/- 0.031, group B: 1.810 +/- 0.029, group C: 2.140 +/- 0.032, P < 0.05 vs. group A) while down-regulated IFN-gamma mRNA (group A: 1.000 +/- 0.061, group B: 0.603 +/- 0.063, group C: 0.333 +/- 0.071, P < 0.01 vs. group A). Serum IFN-gamma, IL-10 concentrations changed in the same direction as myocardial mRNA levels of IFN-gamma, IL-10 post pravastatin treatments.</p><p><b>CONCLUSION</b>Pravastatin treatments upregulated expressions of Cx43 at mRNA and protein levels and improved the INF-gamma/IL-10 balance which might be the working mechanisms for pravastatin-mediated anti-VMC and anti-arrhythmia effects in this VMC model.</p>
Subject(s)
Animals , Male , Mice , Connexin 43 , Metabolism , Coxsackievirus Infections , Drug Therapy , Metabolism , Disease Models, Animal , Interferon-gamma , Metabolism , Interleukin-10 , Metabolism , Mice, Inbred BALB C , Myocarditis , Drug Therapy , Metabolism , Virology , Myocardium , Metabolism , Pravastatin , Therapeutic UsesABSTRACT
Cardiac toxicity is found in frequently used chemotherapeutic agents.There are many factors related to the cardiac toxicity caused by chemotherapeutic agents.The common cardiovascular complications include heart failure,ischemia,hypertension,hypotension,edema,QT prolongation,pleural effusion,pericardial effusion,bradyarrhythmia and thromboembolism.It is necessary to monitor the left ventricular function before and after chemotherapy and take effective measures to protect myocardium.
ABSTRACT
<p><b>OBJECTIVE</b>We observed the therapeutic effectiveness and safety of different antidepressants as well as the correlation between symptomatic improvement of depression and improvement of chest pain in patients with susceptible "angina pectoris" and negative coronary angiogram complicating comorbid depression.</p><p><b>METHODS</b>In this double-blinded randomized study, a total of 123 eligible patients were allocated into three groups: (1) Group F: fluoxetine 20 mg QN (n = 41); (2) Group P: Placebo 1 tablet QN (n = 40); (3) Group F + O: fluoxetine 20 mg + olanzapine 2.5 mg QN for the former 2 weeks and only fluoxetine 20 mg QN for the latter 2 weeks (n = 42). The total therapy duration was 4 weeks. HAMD, HAMA and self-evaluation table of chest pain were obtained before therapy, at the end of 1 and 2 weeks after therapy.</p><p><b>RESULTS</b>Baseline HAMD and HAMA scores and self-evaluation score of chest pain were similar among 3 groups and all scores were significantly improved post various therapies in the order of group F + O > group F > group P. The rate of score decrease were seen after 1 week treatment in group F + O and after 2 week treatment in group F. There was a significant positive correlation between the rates of self-evaluation chest pain score decrease and HAMD (r = 0.867, P < 0.001) and HAMA (r = 0.854, P < 0.001) score decreases after 4 weeks therapies (P < 0.05). During the whole course of treatment, no serious adverse reaction was found in all patients.</p><p><b>CONCLUSION</b>In patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression, the antidepressants were safe and significantly improved the symptoms of depression and anxiety and chest pain. Low dose fluoxetine plus short term olanzapine regimen was superior to fluoxetine alone regimen in terms of stronger and quicker symptom improvement.</p>