Heart dysfunction in patients with acute ischemic stroke or TIA does not predict all-cause mortality at long-term follow-up.

BACKGROUND: Despite heart failure being a substantial risk factor for stroke, few studies have evaluated the predictive value of heart dysfunction for all-cause mortality in patients with acute ischemic stroke, in particular in the elderly. The aim of this study was to investigate whether impaired heart function in elderly patients can predict all-cause mortality after acute ischemic stroke or transient ischemic attack (TIA). METHODS: A prospective long-term follow-up analysis was performed on a hospital cohort consisting of n = 132 patients with mean age 73 ± 9 years, presenting with acute ischemic stroke or transient ischemic attack, without atrial fibrillation. All patients were examined by echocardiography during the hospital stay. Data about all-cause mortality were collected at the end of the follow-up period. The mean follow-up period was 56 ± 22 months. RESULTS: In this cohort, 58% of patients with acute ischemic stroke or TIA had heart dysfunction. Survival analysis showed that heart dysfunction did not predict all-cause mortality in this cohort. Furthermore, in multivariate regression analysis age (HR 5.401, Cl 1.97-14.78, p < 0.01), smoking (HR 3.181, Cl 1.36-7.47, p < 0.01), myocardial infarction (HR 2.826, Cl 1.17-6.83, p < 0.05) were independent predictors of all-cause mortality. CONCLUSION: In this population with acute ischemic stroke or TIA and without non-valvular atrial fibrillation, impaired heart function does not seem to be a significant predictor of all-cause mortality at long-term follow-up.

Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction.

BACKGROUND: High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI. METHODS: cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non-ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI. RESULTS: The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%-67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival. CONCLUSIONS: Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.

Limited AT1 Receptor Internalization Is a Novel Mechanism Underlying Sustained Vasoconstriction Induced by AT1 Receptor Autoantibody From Preeclampsia.

Background Angiotensin II type 1 receptor ( AT 1R) autoantibody ( AT 1- AA ) was first identified as a causative factor in preeclampsia. Unlike physiological ligand angiotensin II (Ang II ), AT 1- AA can induce vasoconstriction in a sustained manner, causing a series of adverse effects, such as vascular injury and poor placental perfusion. However, its underlying mechanisms remain unclear. Here, from the perspective of AT 1R internalization, the present study investigated the molecular mechanism of sustained vasoconstriction induced by AT 1R autoantibody. Methods and Results In the current study, we used the vascular-ring technique to determine that AT 1- AA -positive IgG, which was obtained from the sera of preeclamptic patients, induced long-term vasoconstriction in endothelium-intact or endothelium-denuded rat thoracic arteries. The effect was caused by prolonged activation of AT 1R downstream signals in vascular smooth muscle cells, including Ca2+, protein kinase C, and extracellular signal-regulated kinase 1 and 2. Then, using subcellular protein fractionation, cell surface protein biotinylation, and total internal reflection fluorescence, we found that AT 1- AA -positive IgG resulted in significantly less AT 1R internalization than in the Ang II treatment group. Moreover, through use of fluorescent tracing and bioluminescence resonance energy transfer, we found that AT 1- AA -positive IgG cannot induce the recruitment of ß-arrestin1/2, which mediated receptor internalization. Then, the effect of sustained AT 1R activation induced by AT 1- AA -positive IgG was rescued by overexpression of ß-arrestin2. Conclusions These data suggested that limited AT 1R internalization resulting from the inhibition of ß-arrestin1/2 recruitment played an important role in sustained vasoconstriction induced by AT 1- AA -positive IgG, which may set the stage for avoiding AT 1R overactivation in the management of preeclampsia.

ß2-adrenergic receptor autoantibodies alleviated myocardial damage induced by ß1-adrenergic receptor autoantibodies in heart failure.

Aims: ß1-adrenergic receptor autoantibodies (ß1-AAs) and ß2-adrenergic receptor autoantibodies (ß2-AAs) are present in patients with heart failure (HF); however, their interrelationship with cardiac structure and function remains unknown. This study explored the effects of the imbalance between ß1-AAs and ß2-AAs on cardiac structure and its underlying mechanisms in HF. Methods and results: Patients with left systolic HF who suffered from coronary heart disease (65.9%) or dilated cardiomyopathy (34.1%) were divided into New York Heart Association Classes I-II (n = 51) and Classes III-IV (n = 37) and compared with healthy volunteers as controls (n = 41). Total immunoglobulin G from HF patient serum comprising ß1-AAs and/or ß2-AAs were determined and purified for in vitro studies from neonatal rat cardiomyocytes (NRCMs). In addition, HF was induced by doxorubicin in mice. We observed that the increased ratio of ß1-AAs/ß2-AAs was associated with worsening HF in patients. Moreover, ß2-AAs from patients with HF suppressed the hyper-shrinking and apoptosis of NRCMS induced by ß1-AAs from some patients. Finally, ß2-AAs alleviated both myocardial damage and ß1-AAs production induced by doxorubicin in mice. Conclusion: ß2-AAs were capable of antagonizing the effects imposed by ß1-AAs both in vitro and in vivo. The imbalance of ß1-AAs and ß2-AAs in patients with HF is a mechanism underlying HF progression, and the increasing ratio of ß1-AAs/ß2-AAs should be considered a clinical assessment factor for the deterioration of cardiac function in patients with HF.

Does the target dose of neurohormonal blockade matter for outcome in Systolic heart failure in octogenarians?

BACKGROUND: In elderly patients with chronic heart failure (CHF), a gap exists between widespread use of lower doses of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) and ß-blockers (BBs) and guideline recommendations. Therefore, the aim of the present study was to investigate whether patients receiving ≥ 50% target dose outperform those receiving <50% target dose, despite maximum up-titration, and whether the target dose outperforms all other doses. METHODS AND RESULTS: Patients (n=185) aged ≥ 80 years with CHF and left ventricular ejection fraction ≤ 40% referred (between January 2000 and January 2008) to two CHF outpatient clinics at two university hospitals, were included and retrospectively studied. Of the study population, 53% received the target dose of ACEIs/ARBs, whereas 26% received <50% of the target dose. Half received <50% of the target dose of BBs and 21% received the target dose. After ≥ 5 years of follow-up, all-cause mortality was 76.8%. Patients who received the target dose of ACEIs/ARBs had higher survival rates from all-cause mortality than those receiving <50% of target dose (HR=0.6, 95%CI 0.4-0.9, P=0.033), but those receiving ≥ 50% of target dose did not statistically differ from those who achieved target dose. This dose-survival relationship was not the case for BBs. CONCLUSIONS: Target dose of ACEIs/ARBs is associated with reduced all-cause five-year mortality in very old patients with systolic heart failure, despite that this was achievable in only about half of the patients. However, the clinical outcome of BB therapy is independent of BB dose when the target heart rate is achieved.

High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease.

BACKGROUND: Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers. OBJECTIVE: To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers. METHODS: Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomarkers Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid-Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90mL/min/1.73m(2). RESULTS: Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a GFR of 15mL/min/1.73m(2) varied from 2-fold to 15-fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured GFR and increased more at low GFR compared to hs-cTnI. For hFABP and NTproBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations). CONCLUSION: The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations.

Amiodarone minimizes experimental autoimmune myocarditis in rats.

Amiodarone, a promising drug for the treatment of tachyarrythmias, was recently found to have immunomodulatory effects in vitro. We hypothesized that amiodarone would affect the immune system in vivo and examined the effect of amiodarone on myocarditis in rats. We induced experimental autoimmune myocarditis in rats by cardiac myosin immunization and treated the animals with an intraperitoneal injection of amiodarone at 25 mg/kg/every other day, 10 times after the induction of experimental autoimmune myocarditis. In the treated group, both microscopic and macroscopic examinations showed reduced heart weights, a mild and localized infiltration of inflammatory cells and fibrosis in the myocardium, and a mild congestion in the liver and lungs as compared with the control group. The phenotypic distribution of lymphocytes in peripheral blood showed a significant decrease in the CD4/CD8a ratio in the treated group, but not in the control group. The proportion of mast cells involved in inflammatory cell infiltration was lower in the treated group than the control group. In vitro, amiodarone inhibited the proliferation of mast cells by arresting them in the G2 phase of the cell cycle. These results indicated that amiodarone minimized the progression of experimental autoimmune myocarditis, suggesting a potential therapeutic role for amiodarone treatment in patients suffering from myocarditis, especially myocarditis complicated by cardiac arrhythmias. One possible mechanism by which amiodarone minimizes the progression of experimental autoimmune myocarditis may be to affect the immune system via the immunomodulatory effects on T cell and mast cell functions.

Clinical significance and pathogenic role of anti-cardiac myosin autoantibody in dilated cardiomyopathy.

OBJECTIVE: In order to explore the possible roles played by the autoimmune mechanism in the progression of myocarditis into dilated cardiomyopathy (DCM) using an animal model, we investigated whether autoimmune myocarditis might develop into DCM. METHODS: Experimental Balb/C mice (n = 20) were immunized with cardiac myosin with Freund's complete adjuvant at days 0, 7 and 30. The control Balb/C mice (n = 10) were immunized with Freund's complete adjuvant in the same mannere. Serum and myocardium samples were collected after the first immunization at days 15, 21 and 120. The anti-myosin antibody was examined by enzyme-linked immunosorbent assay and immunoblotting. RESULTS: Pathological findings demonstrated that there was myocardial necrosis or inflammatory infiltration during acute stages and fibrosis mainly in the late phase of experimental group, but the myocardial lesions were not found in the control group. Autoimmunity could induce myocarditis and DCM in the absence of viral infection. High titer anti-myosin IgG antibodies were found in the experimental group, but not in the control group. Furthermore, the anti-myosin heavy chain (200 KD) antibody was positive in 21 of 48 patients with DCM and viral myocarditis, but only 4 of 20 patients with coronary heart disease, including 1 case and 3 cases that reacted with heavy and light chains (27.5 KD), respectively. The antibodies were not detected in healthy donors. CONCLUSION: Cardiac myosin might be an autoantigen that provokes autoimmunity and leads to the transformation of myocarditis into DCM. Detection of anti-myosin heavy chain antibody might contribute to diagnosis for DCM and viral myocarditis.

Assessment of a multimarker strategy for prediction of mortality in older heart failure patients: a cohort study.

OBJECTIVE: Primarily to develop a multimarker score for prediction of 3-year mortality in older patients with decompensated heart failure (HF). DESIGN: Prospective cohort study. SETTING: Secondary care. Single centre. PATIENTS AND BIOMARKERS: 131 patients, aged ≥65 years, with decompensated HF were included. Assessment of biomarkers was performed at discharge. PRIMARY OUTCOME MEASURE: 3-year mortality. RESULTS: Mean age was 73±11 years; mean left ventricular ejection fraction , 43±14%; 53% were male. The 3-year mortality was 53.4%. The following N-terminal brain natriuretic peptide (NTproBNP) levels could optimally stratify mortality: <2000 ng/l (n=39), 30.8% mortality; 2000-8000 ng/l (n=58), 51.7% mortality; and >8000 ng/l (n=34), 82.4% mortality. However, in the 2000-8000 ng/l range, NTproBNP levels had low-prognostic capacity, based on the area under the receiver operating characteristic curve (AUC=0.53; 95% CI 0.40 to 0.67). In this group, multivariate analysis identified age, cystatin C (CysC), and troponin T (TnT) levels as independent risk factors. A risk score based on these three risk factors separated a high-risk and low-risk groups within the NTproBNP range of 2000-8000 ng/l. The score exhibited a significantly higher AUC (0.75; 95% CI 0.62 to 0.86) than NTproBNP alone (p=0.03) in this NTproBNP group and had similar prognostic capacity as NTproBNP in patients below or above this NTproBNP range (p=0.57). Net reclassification improvement and integrated discriminatory improvement in the group with NTproBNP levels between 2000 and 8000 ng/l was 54% and 23%, respectively, and in the whole cohort 22% and 11%, respectively. CONCLUSIONS: Our results suggested that, to assess risk in HF, older patients required significantly higher levels of NTproBNP than younger patients. Furthermore, a risk score that included TnT and CysC at discharge, and age could improve risk stratification for mortality in older patients with HF in particular when NTproBNP was moderately elevated.

Small changes in troponin T levels are common in patients with non-ST-segment elevation myocardial infarction and are linked to higher mortality.

OBJECTIVES: The purpose of this study was to examine the extent of change in troponin T levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Changes in cardiac troponin T (cTnT) levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20% to 230% and an absolute change of 7 to 9 ng/l have been suggested as cutoff points. METHODS: In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitivity cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1,178 patients with a final diagnosis of NSTEMI presenting <24 h after symptom onset. RESULTS: After 6 h of observation, the relative change in the hs-cTnT level remained <20% in 26% and the absolute change <9 ng/l in 12% of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p = 0.002) and in multivariate analyses (hazard ratio: 1.61 [95% confidence interval: 1.17 to 2.21], p = 0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change. CONCLUSIONS: Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.

Red blood cell distribution width and its relation to cardiac function and biomarkers in a prospective hospital cohort referred for echocardiography.

BACKGROUND: Red blood cell distribution width (RDW), a measure of anisocytosis, is a prognostic biomarker for heart failure (HF). However it is still unclear how RDW is associated with heart function and established cardiac biomarkers. METHODS AND RESULTS: In a prospective hospital cohort of 296 patients referred for echocardiography because of suspected HF, blood sampling and clinical examination were performed within 24h after echocardiography. The patients were divided into four HF groups, including one group where the HF diagnosis was uncertain (gray zone). In the patients the mean age was 70 ± 11 years, 44% with systolic HF (SHF), 18% with heart failure with normal ejection fraction (HFNEF), 17% with gray zone and 21% without HF (non-HF). RDW was higher among patients with SHF and HFNEF, compared with gray zone and non-HF patients. The distribution of different variables over the RDW quartiles showed an inverse correlation between RDW levels and LVEF and a positive correlation between RDW and NT-proBNP levels. Further analysis with stepwise multiple linear regression demonstrated that NT-proBNP levels, but not LVEF, were independently correlated with RDW. CONCLUSION: In patients referred for echocardiography because of suspected HF, RDW levels were higher in patients with SHF and HFNEF. Moreover, NT-proBNP levels were independently linked with elevated RDW.

Prognostic values of NTpro BNP/BNP ratio in comparison with NTpro BNP or BNP alone in elderly patients with chronic heart failure in a 2-year follow up.

BACKGROUND: Plasma BNP and NT-proBNP are often used as interchangeable parameters in heart failure care in clinical practice. In our previous study we have shown that inflammation was able to induce increased NT pro BNP in a hospital cohort with chronic heart failure in the elderly, indicating that NT-proBNP/BNP ratio should be evaluated concomitantly with inflammatory status to avoid overestimation of heart failure severity. The present study was aimed to evaluate the clinical significance of NT-proBNP/BNP ratio in comparison with NTpro BNP or BNP alone as a prognostic indicator in a 2-year follow up of elderly heart failure population. MATERIALS AND METHODS: One hundred and eight-nine elderly heart failure patients (72 ± 11 years, male 52%, LVEF 46 ± 14%) were enrolled consecutively during 2006 and 2007 and followed up during 2 years. NTpro BNP and BNP were measured routinely. RESULTS: We have found that NTpro BNP/BNP ratio provides no additional prognostic information during follow up as compared to NTpro BNP or BNP alone in an elderly population with chronic heart failure. By the use of ROC curves, for total mortality predictive accuracy during 2 years, the cut-off values are NTproBNP ≥ 800 pg/ml, BNP > 60 pg/ml and NTpro BNP/BNP ratio>6.4 respectively. In terms of NTpro BNP, as long as its serum level is above 2000 pg/ml it indicates poor prognosis. However there is an overlap between serum concentration range 2000-8000 pg/ml and >8000 pg/ml in terms of prognostic indicator. Similarly for BNP, as long as its serum level is above 100 pg/ml, it indicates poor prognosis. However there is an overlap between serum concentration range 100-800 pg/ml and >800 pg/ml in terms of prognostic indicator. There was significant correlation between survival and NTpro BNP, BNP and Cystatin-C but not with NTpro BNP/BNP ratio. Such correlation exists irrespective of subgroups regardless of less than or older than 70 years old. CONCLUSIONS: Our results demonstrated that in elderly heart failure population NTpro BNP/BNP ratio may provide diagnostic help in the presence of acute infection but no additional prognostic information in the long run as compared with NTpro BNP or BNP alone. Furthermore, both NTpro BNP and BNP are useful prognostic biomarkers indeed but they need to be interpreted with caution when it is used as a single biomarker and in the meantime concomitant diseases exist because patients may die due to non-cardiac causes.

Cystatin C in a composite risk score for mortality in patients with infective endocarditis: a cohort study.

OBJECTIVE: To develop a multimarker prognostic score for infective endocarditis (IE). DESIGN: Retrospective case-control. SETTING: Secondary care. Single centre. PARTICIPANTS: 125 patients with definite IE. PRIMARY OUTCOME MEASURES: 90-day and 5-year mortality. RESULTS: Mean age was 62.7±17 years. The 90-day and 5-year mortality was 10.4% and 33.6%, respectively. CysC levels at admission and over 20% increases in CysC levels during 2 weeks of treatment were prognostic for 90-day and 5-year mortality independent of creatinine estimated glomerular filtration rate. In multivariate analyses, CysC (OR 5.42, 95% CI 1.90 to 15.5, p=0.002) and age (OR 1.06, 95% CI 1.02 to 1.10, p=0.002) remained prognostic for 5-year mortality. NT-proBNP, TnT, C reactive protein and interleukin 6 were also linked to prognosis. A composite risk scoring system using levels of CysC, NT-proBNP, age and presence of mitral valve insufficiency was able to separate a high-risk and a low-risk group. CONCLUSIONS: CysC levels at admission and increase in CysC after 2 weeks of treatment were independent prognostic markers for both 90-day and 5-year mortality in patients with IE. A multimarker composite risk scoring system including CysC identified a high-risk group.

Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio.

Plasma BNP and NT-proBNP are often regarded as interchangeable parameters in assessing heart failure (HF) severity and prognosis. Renal failure results in disproportionate increases of NT-proBNP and an increased NT-proBNP/BNP ratio. Low kidney function is therefore considered particularly when NT-proBNP is used to assess HF. The purpose of this study was to identify other conditions affecting the NT-proBNP/BNP ratio. We examined the NT-proBNP/BNP ratio, 26 other lab parameters, and clinical factors in 218 patients admitted to the HF ward. In addition to renal function, we also found significant correlations between the NT-proBNP/BNP ratio and inflammation as measured by orosomucoid (r = 0.525, p < 0.0001), CRP (r = 0.333, p < 0.0001), haptoglobulin (r = 0.201, p = 0.02), and alpha1-antitrypsin (r = 0.223, p = 0.01). Reverse correlation was found with transferrin (r = -0.323, p < 0.0001), albumin (r = -0.251, p = 0.003), and S-Fe (r = -0.205, p = 0.02), parameters known to decrease during inflammation. Inflammation increased levels of NT-proBNP more than BNP, resulting in an increased NT-proBNP/BNP ratio. Our findings indicate that NT-proBNP should be evaluated concomitantly with inflammatory status to avoid overestimation of HF severity.

Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors.

The effects of methoxamine, a selective alpha1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of alpha1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of alpha1-adrenoreceptors significantly increased the L-type calcium current (I(Ca(L))) but had no effect on the T-type calcium current (I(Ca(T))), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective alpha1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in I(Ca(L)), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional alpha1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of alpha1-receptor agonists like methoxamine.

Prevention of myosin-induced autoimmune myocarditis in mice by anti-L3T4 monoclonal antibody.

This study was aimed at studying the effect of the induction of immune tolerance to swine cardiac myosin from anti-L3T4 monoclonal antibody injection and whether the immune tolerance could protect mice with myosin-induced myocarditis from myocardial injury. Twenty-four Balb/c mice were divided into two groups at random. All of the mice were immunized with swine cardiac myosin on the 1st day, 14th, 28th, 42nd, and 52nd day. Immune tolerance was induced by triplicate injections of 400 microg anti-L3T4 McAb on the 0 day (intravenous), 1st day, and 2nd day (intraperitoneal) in McAb-treated group. In the saline-treated group, saline of the same volume as anti-L3T4 monoclonal antibody was used as a control. The sera and hearts biopsies of all mice were collected on the 58th day. The anti-cardiac myosin antibody was examined with ELISA, and pathological changes of heart were observed by light microscope. It was shown that mice immunized with swine cardiac myosin could produce anti-myosin antibody and the anti-cardiac myosin antibody was positive in most of the saline-treated group but negative in the McAb-treated group. Morphologically, myocardial degeneration, necrosis, and infiltration of inflammatory cells were found in the saline-treated group but not in the McAb-treated group. In conclusion, this study indicated that the immune tolerance to cardiac myosin was induced by the anti-L3T4 monoclonal antibody, and accordingly myocardial injury could be prevented by induction of immune tolerance.