RESUMO
Chagas' disease, induced by Trypanosoma cruzi , is a common cause of infectious myocarditis. Recent clinical treatment trials and vaccine studies indicate that chagasic immunopathology is directed against the parasite and not self-antigens. Therefore, vaccines may have the potential to protect against disease progression. Certain combinations of mouse and parasite strains produce significant histopathology and can be used for safety analyses of new vaccination strategies. The goals of this study were to determine (1) whether the development of chagasic cardiomyopathy in the murine model could be identified by electrocardiogram (ECG); and (2) whether these potential chagasic ECG changes would correlate with histopathologic findings. Groups of BALB/c, C57BL/6, and C3H mice were infected with different parasite strains (Tulahuén, Brazil, or Sylvio-X10/4) and evaluated weekly by ECG. Selected tissues from subsets of mice were harvested periodically for blinded histologic evaluation. Significantly increased proportions of BALB/c mice infected with Brazil and Tulahuén strain parasites displayed prolonged QT intervals. Prolonged mean QT intervals detected in infected BALB/c mice significantly correlated with chagasic histopathologic changes. These results indicate that ECG can be used as a non-invasive method to screen for immune-mediated damage resulting in chagasic cardiomyopathy in the murine model.
Assuntos
Cardiomiopatia Chagásica/diagnóstico , Eletrocardiografia , Animais , Cardiomiopatia Chagásica/patologia , Modelos Animais de Doenças , Feminino , Inflamação/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos SCID , Músculo Esquelético/patologia , Miocárdio/patologia , Estatísticas não ParamétricasRESUMO
OBJECTIVES: The authors sought to define the risks versus benefits of ultrasound contrast agents in patients undergoing stress echocardiography. BACKGROUND: The Food and Drug Administration recently placed a "black box" warning on the ultrasound contrast agents Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) and Optison (GE Healthcare, Princeton, New Jersey) after their use was temporally related to 4 deaths. The safety of contrast has not been systematically evaluated. METHODS: We retrospectively analyzed 42,408 patients at 3 different institutions who had baseline suboptimal images and/or underwent myocardial perfusion imaging and received contrast agents; 18,749 of these underwent stress echocardiography. The outcomes (death and myocardial infarction [MI]) within 30 min, 24 h, and during long-term follow-up were recorded. RESULTS: No deaths or MIs were observed within 30 min; 1 death and 5 nonfatal MIs were observed within 24 h. This was not different from a matched cohort of 15,989 patients not receiving contrast. At 1 h and at 30 days after contrast administration, no significant differences in death rates or MIs were observed between patients who did and did not receive contrast during their stress echocardiogram. Endocardial border visualization in patients with suboptimal images resulted in comparable sensitivity (81% vs. 73%, p = NS) and diagnostic accuracy (82% vs. 77%, p = NS) for wall motion analysis compared with patients with optimal image quality. At long-term follow-up, abnormal wall motion and/or myocardial perfusion predicted adverse outcomes (20.6%) when compared with patients with normal studies (3.7%). CONCLUSIONS: Despite recent warnings regarding echocardiographic contrast, our findings indicate it is a safe and useful diagnostic tool in assessment of patients suspected of having coronary artery disease.