Brain natriuretic peptide--a reliable parameter for the effectiveness of cardiac resynchronization therapy after coronary artery bypass grafting.

OBJECTIVES: Brain natriuretic peptide (BNP) is a valuable marker in heart failure and its therapy, for example cardiac resynchronization therapy (CRT). So far, one finding which is indicative for CRT is dyssynchrony of ventricular contraction obtained by echocardiography. The aim of this study was to show that BNP is also a helpful marker to help decide whether CRT is useful for patients after CABG. METHODS: Forty-two patients with a poor ejection fraction (<35%) underwent elective CABG. Twenty-eight of them received permanent biventricular stimulation for seven days after surgery. Before and on the first, third, seventh and tenth day after surgical treatment, the following parameters were established: left ventricular function obtained by transthoracic echocardiography, myocardium-specific enzymes (such as CK and CKMB), ECG and BNP. RESULTS: There was a very good correlation between the preoperative ejection fraction and BNP (r2=0.98, P<0.005). Patients who had received CRT after CABG had BNP levels similar to preoperative data on postoperative day 7. This decrease of the BNP values in the CRT-group is in accord with an increased left ventricular function as obtained by echocardiography. The control group, which had not received CRT, showed significantly higher BNP levels. CONCLUSIONS: Therefore, we conclude that BNP is a good marker to evaluate CRT in patients undergoing CABG. An extraordinary rise of the BNP level should lead to early therapeutic consequences like CRT. The significantly lower BNP level of the patients with heart failure who received CRT indicates a better prognosis.

Differential downregulation of endoplasmic reticulum-residing chaperones calnexin and calreticulin in human metastatic melanoma.

Characterization of the molecular basis of tumor recognition by T cells has shown that major histocompatibility complex (MHC) class I molecules play a crucial role in presenting antigenic peptide epitopes to cytotoxic T lymphocytes. MHC class Ia downregulation has been repeatedly described on melanoma cells and is thought to be involved in the failure of the immune system to control tumor progression. Proper assembly of MHC class I molecules is dependent on several cofactors, e.g. the chaperones calnexin and calreticulin residing in the endoplasmic reticulum. Alterations in the expression of these chaperones may have important implications for MHC class I assembly, peptide loading, and presentation on the tumor cell surface and thus may contribute to the immune escape phenotype of tumor cells. In the present study, we compared melanoma lesions representing different stages of tumor progression with regard to the expression of calnexin and calreticulin in tumor cells by means of immunohistochemistry. Metastatic melanoma lesions exhibited significant downregulation of calnexin as compared to primary melanoma lesions. In contrast, chaperone calreticulin was expressed in melanoma cells of primary as well as of metastatic lesions. Our data suggest that chaperone-downregulation, particularly calnexin-downregulation, may contribute to the metastatic phenotype of melanoma cells in vivo. Consistently, conserved chaperone expression in metastatic melanoma lesions may be a useful criterion for selection of patients for treatment with T cell-based immunotherapies.