The effects of cyclophosphamide on experimental viral myocarditis

BACKGROUND: Viral myocarditis is considered as a cause of dilated cardiomyopathy. At present, two pathogenic mechanisms may be involved in the pathogenesis of viral myocarditis and subsequent cardiomyopathy. First, the virus infection of myocyte may directly lead to either cell death or persistent metabolic dysfunction. Second, virus-induced immune or autoimmune mechanism may play a role. METHODS: To test the therapeutic efficacy of immunosuppression with cyclophophamide(CYP) on coxsackievirus B3(CB3) myocarditis, 10-14 week-old Balb/c mice were inoculated with 4000 plaque-forming units of CB3. In experiment 1, CYP (100mg/kg/day subcutaneous injection, s.c) was administrated daily on days 1-7(group 2, n=16). In experiment 2, CYP 30mg/kg/day s.c(group 3, n=32) or CYP 100mg/kg/day s.c(group 4, n=32) were administrated on days 8-14. The animals of infected controls(group 1, n=26) and group 2, 3, 4 were dissected at days 4, 7, 15, 22 and spleen, heart, thymus and body weights were measured. RESULTS: In experiment 1. survival rate in group 2 on day 7, 15 were low compared with group 1(85%, 0% vs 100%, p<0.05). and myocardial virus titers in group 2 on day 4 was 50 times, and on day 7, 1000 times higher compared with group 1, Histologically, on day 7, focal cellular infiltrations were prominent findings in group 1, but diffuse myocardial necrosis without cellular infiltration were observed in group 2. In experiment 2, survival rate, cardiac histopathology myocardial virus titer and serum neutralizing antibody titers did not differ among groups 1, 3 and 4. In experiment 1 and 2, the spleen-to-body-weight and thymus-to-body-weight ratios were significantly lower in CYP treated groups than those in controls and marked cellular depletions in spleens and thymus were observed in CYP treated groups. CONCLUSIONS: As the results of above, it can be concluded that the immunosuppression during viremic phase of murine viral myocarditis aggravated the myocardial necrosis, and during aviremic phase, the administration of CYP didnot affect the process of viral myocarditis. Thus, direct viral mechanisms in the production of cardiomyocyte injury in CB3-infected mice appear to bo more important than cell mediated immune mechanism. To understand relevant pathogenic mechanisms of clinical myocarditis and dilated cardiomyopathy resulting from viral infection, the experimental study expanding into nonmurine animals and into various models using other infectious agents may be required.

Echocardiographic Evaluation of Regional Wall Motion Nonuniformity and Phase Difference in Asymmetric Septal Hypertrophy

BACKGROUND: A regional wall motion nonuniformity and a phase difference between LV posterior wall motion and transmitral flow are present during normal rapid filling period and are thought to be an evidence for involvement of ventricular restoring forces. To assess the role of nonuniformity on diastolic funtional impairment of asymmetric septal hypertrophy(ASH), the time relations between left ventricular regional wall motions and filling velocity were studied. METHOD: We measured the time intervals from A2 to peak rate of LV posterior wall(short axis) thinning(A2-(-)dpw/dt), peak rate of medial mitral annulus (long axis dimension) lengthening(A2-dL/dt) and peak mitral flow(A2-E) by M-mode and Doppler echocardiography. Result: In ASH patients, A2-(-)dpw/dt(106+/-6msec, mean SE) and the regional wall motion nonuniformity((-)dpw/dt-dL/dt, 89+/-11msec, mean SE) were increased significantly when compared with normal control values(88+/-4, 28+/-5msec, mean SE, p<0.01,respectively).In normal controls, peak mitral flow velocity lagged peak rate of regional wall motion, so the phase differences were present((-)dpw/dt-E :71+/-8msec, dL/dt-E:44+/-6msec). In ASH patients, (-)dpw/dt-E was present(90+/-16msec) but dL/dt-E was not present or reversed(-21+/-18 msec). So these chacteristic phase differences were disturbed. CONCLUSION: These data suggested that the relaxation nonuniformity of regional wall motion in ASH may act as an energy dissipating factor of restoring forces during rapid filling period.

Echocardiographic Measurement of Early Diastolic Time Intervals in Patients with Hypertension: With Reference to Regional Nonuniformity and Restoring Forces

BACKGROUND: It is known that left ventricular(LV) wall motion is not uniform even in normal heart, and the restoring forces make phase differences between LV wall motion and mitral flow velocity during rapid filling period. METHOD: To investigate the regional nonuniformity and restoring forces in 46 patients with hypertension(HT)(group:normal wall thickiness.n=12,II:LVH with fractional shortening(FS)>25%. n=22. III:FS<25%.n=12). We measured the time intervals from A2 to peak thinning rate point of LV posterior wall(A2-(-)dpw/dt).to mitral flow starting point (IRT).and to peak mitral flow velocity(A2-E) by M-mode and Doppler echocardiography. RESULTS: The noniformity((-)dpW/dt-dL/dt)and phase differance((-)dpw/dt-E) were increased in HT(control:HT.22+/-7.8 vs. 49+/-5.2msec, 63+/-4.5 vs, 86+/-6.2msec, p<0.05 respectively).In group comparison, nonuniformity increased in group II and III(group I: group II, III, 35+/-5.1 vs. 50+/-7.1,70+/-14msec, p<0.05 respectively). but phase difference increased only in group II(groupII: group I, III, 93+/-6.0 vs. 75+/-5.2, 80+/-20msec, p<0.05, respectively). CONCLUSION: We interpreted these data that in HT with hypertrophy or not, the nonuniformity of LV wall motion working on the restoring forces which can be expressed as phase difference between LV wall motion and mitral flow. But in HT with hypertensive heart failure group, no significant changes of phase difference and it's suggest that other mechanism could be also working on early diastolic filling.

Immunologic classification of acute lymphocytic leukemia in children and its prognosis / 대한혈액학회지

No abstract available.