Immunoglobulin treatment ameliorates myocardial injury in experimental autoimmune myocarditis associated with suppression of reactive oxygen species.

[Aims]We tested the hypothesis that immunoglobulin ameliorated experimental autoimmune myocarditis (EAM) in mice attributing to the suppression of reactive oxygen species (ROS)-mediated myocardial injury. [Methods]We intraperitoneally administered intact type of human immunoglobulin (Ig) or F(ab′)2 fragments of human immunoglobulin, 1 g/kg/day daily for 3 weeks, to male BALB/c mice with heart failure due to EAM. [Results]The results showed that intact type of Ig, but not F(ab′)2 type, reduced the severity of myocarditis by comparing the heart weight/body weight and lung weight/body weight ratios, pericardial effusion score, macroscopic and microscopic scores. Tissue superoxide production was marked in untreated mice with EAM, which was suppressed by the treatment of immunoglobulins. The cytotoxic activities of lymphocytes in mice with EAM treated with Ig were reduced compared with untreated controls. The shift from Th1 toward Th2 cytokine balance was demonstrated by the treatment of immunoglobulins both in vitro and in vivo. [Conclusion]ROS may be involved in the development of myocarditis. Intact Ig ameliorates myocardial damage in mice with myocarditis associated with suppression of ROS and cytotoxic activity of lymphocytes

Tall P waves associated with severe hypokalemia and combined electrolyte depletion.

A 32-year-old woman with anorexia nervosa showing tall P waves on electrocardiogram (ECG) was reported. Her ECG showed tall P waves (5.5mm in voltage, lead II) at 2.2mEq/L of serum potassium. After the treatment, P waves decreased in voltage with the normalization of serum potassium. Tall P waves may be considered to be the so-called pseudo-P pulmonale, and added to the criteria of hypokalemia on ECG

Carvedilol reduces the severity of atherosclerosis in apolipoprotein E-deficient mice via reducing superoxide production.

It has been shown that oxidative stress may play an important role in the development of atherosclerosis, and carvedilol has the capacity of reducing oxidative stress. Accordingly, we assessed the hypothesis that carvedilol may reduce the severity of atherosclerosis in apolipoprotein E (apoE)-deficient mice in addition to its hemodynamic effects. Atherosclerosis was induced in apoE-deficient mice fed a high-fat diet containing 0.3% cholesterol. Mice were orally treated with propranolol (30 mg/kg/day), metoprolol (75 mg/kg/day) and carvedilol (10 mg/kg/day) over eight weeks (each group n = 7-9). Fatty streak plaque developed in apoE-deficient mice, and was suppressed in mice treated with all three drugs. The accumulation of macrophages and expression of CD4(+) and CD8(+) cells in the lesions were decreased by the treatment of the drugs, of which carvedilol was the most effective. In addition, carvedilol reduced superoxide production in aortic walls detected by ethidium staining. There were no significant changes in blood pressure among the study groups. The heart rates in the treated groups were decreased by 4%-12% compared with the control group, with carvedilol yielding the highest suppression of heart rate. The β-blocker treatment did not significantly modify the serum lipid profiles. Carvedilol may suppress atherosclerosis via reducing superoxide production, in addition to the hemodynamic modifications in this animal model

Atherosclerotic plaques induced by marble-burying behavior are stabilized by exercise training in experimental atherosclerosis.

Background： We assessed the hypothesis whether behavioral stress may affect the development of atherosclerosis and whether regular exercise training may influence the composition of atherosclerotic plaques in apolipoprotein (apo) E-deficient mice.　　Methods： Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Exercise training (45 min swimming, 3 times/week) was conducted, and behavioral stress was provoked by glass marble-burying procedure. Mice were treated with marble-burying, marble-burying behavior plus swimming training, and swimming alone over 8 weeks.　　Results： Exercise training decreased the atherosclerotic lesions, but marble-burying behavior increased the lesions. The plaques containing macrophage accumulation with intercellular adhesion molecule-1 (ICAM-1) expression associated with reduced collagen contents were induced in the mice treated with marble-burying. However, ICAM-1 expression was suppressed and collagen contents were reversed in the mice that received marble-burying behavior plus exercise training. In addition, exercise alone and concomitant exercise training reduced the superoxide production in aortic walls, shown by dihydroethidium staining, compared with that in mice with marble-burying behavior alone. There were no significant differences in the serum lipids profiles among the groups.　　Conclusions： Behavioral stress increased the atherosclerotic lesions and induced the adhesion molecule expression with superoxide production on the lesions in apo E-deficient mice. Exercise training may stabilize plaque lesions induced by marble-burying behavior in this animal model

Erythromycin treatment suppresses myocardial injury in autoimmune myocarditis in rats via suppression of superoxide production.

[Background]Recent evidence suggests that erythromycin (EM), a major macrolide antibiotic, has many biological functions in addition to the anti-bacterial actions, including anti-inflammatory and free radical scavenging actions. However, the effects of the drug upon inflammatory myocardial diseases are unknown. We tested the hypothesis that EM ameliorates experimental autoimmune myocarditis in rats attributing to the suppression of superoxide production. [Methods]We administered EM, 3.3 mg/kg/day and 33 mg/kg/day, intraperitoneally for 3 weeks, to rats with experimental autoimmune myocarditis (EAM) produced by immunization by porcine myosin. [Results]EM treatment reduced the severity of myocarditis compared with the untreated group in a dose-dependent manner by comparing the heart weight/body weight ratio, pathologic scores, and myocardial macrophage, CD4+, and CD8+ infiltrations. Echocardiographic study showed that increased left ventricular posterior wall thickness produced by myocardial inflammation was reduced by EM treatment. Myocardial superoxide production, determined by dihydroethidium staining, was significantly reduced by the treatment. Western blotting showed that the expression of myocardial interleukin-1β was reduced by EM treatment compared with untreated groups. The in vivo dorsal air pouch model showed that EM significantly suppressed leukocyte chemotaxis in a dose-dependent manner. [Conclusion]Irrespective of a well-known classic antibiotic, EM attenuated EAM not only by the anti-inflammatory action but by the suppression of superoxide production