The Na(+)/Ca(2+) exchanger (NCX) may influence cardiac function depending on its predominant mode of action, forward mode or reverse mode, during the contraction-relaxation cycle. The intracellular Na(+) concentration ([Na(+)](i)) and the duration of the action potential as well as the level of NCX protein expression regulate the mode of action of NCX. [Na(+)](i) and NCX expression have been reported to be increased in human heart failure. Nevertheless, the consequences of altered NCX expression in heart failure are still a matter of discussion. We aimed to characterize the influence of NCX expression on intracellular Ca(2+) transport in rat cardiomyocytes by adenoviral-mediated gene transfer. A five- to ninefold (dose dependent) overexpression of NCX protein was achieved after 48 h by somatic gene transfer (Ad.NCX.GFP) versus control (Ad.GFP). NCX activity, determined by Na(+) gradient-dependent (45)Ca(2+)-uptake, was significantly increased. The protein expressions of sarco(endo)plasmic reticulum Ca(2+)-ATPase, phospholamban, and calsequestrin were unaffected by NCX overexpression. Fractional shortening (FS) of isolated cardiomyocytes was significantly increased at low stimulation rates in Ad.NCX.GFP. After a step-wise enhancing frequency of stimulation to 3.0 Hz, FS remained unaffected in Ad.GFP cells but declined in Ad.NCX.GFP cells. The positive inotropic effect of the cardiac glycoside ouabain was less effective in Ad.NCX.GFP cells, whereas the positive inotropic effect of beta-adrenergic stimulation remained unchanged. In conclusion, NCX overexpression results in a reduced cell shortening at higher stimulation frequencies as well as after inhibition of sarcolemmal Na(+)-K(+)-ATPase, i.e., in conditions with enhanced [Na(+)](i). At low stimulation rates, increased NCX expression enhances both intracellular systolic Ca(2+) and contraction amplitude.

Cardiac glycosides like ouabain are used in the therapy of heart failure and atrial fibrillation. They exert a positive inotropic effect on cardiomyocytes by inhibiting the plasma membrane sodium pump (Na,K-ATPase), decreasing the Ca-extrusion by the sarcolemmal cardiac sodium/calcium exchanger (NCX) and increasing the intracellular Ca-concentration and Ca-release during subsequent contraction cycles.The longer term effects of ouabain treatment on the expression of proteins important for Ca- and Na-homeostasis are not well known and were investigated in this study. Isolated adult rat cardiomyocytes were cultured in the presence or absence of ouabain (30 microM). In these cells, the expression of the Na,K-ATPase, Na,Ca-exchanger (NCX), the sarcoplasmic reticulum Ca-ATPase (SERCA 2a) and phospholamban (PLB) were studied by Western blot. In addition, the contractile function of these cells was studied after electrical stimulation. After 2 days of ouabain treatment immunoreactivity of the NCX was increased significantly relative to control which was set 1 (1.78 +/- 0.16 vs. 1 +/- 0.13; n = 8; P = 0.003) and at day 4 (1.96 +/- 0.35 vs. 1 +/- 0.20; n = 6; P = 0.02). All other proteins (SERCA 2a, PLB and Na,K-ATPase a1 and b1) remained unchanged (n>/= 4). Ouabain treatment increased the fractional shortening of isolated cardiomyocytes at day 0 (1 Hz: 9.64 +/- 0.73 %, n = 24, vs. 7.18 +/- 0.60 %; n = 21; P = 0.01), whereas at day 2 the contractility was unchanged (1 Hz: 7.23 +/- 1.08 %, n = 9 vs. 7.70 +/- 0.63 %; n = 10, P = 0.71). The inhibition of SERCA 2a (10 microM cyclopiazonic acid (CPA)) decreased contractility in both the ouabain treated group and in controls, at day 0 and at day 2. These results show that chronic ouabain treatment increases the protein expression of the NCX. The positive inotropic effect of ouabain can no longer be observed after a chronic treatment for 2 days. Thus, both protein expression and contractile function of the cells are specifically altered by longer term cardiac glycoside exposure. Whether such regulation can be found in human cardiomyocytes and the resulting consequences in the clinical setting remain to be determined.

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Adenocarcinoids are rare tumors with histological features of both carcinoid tumor and adenocarcinoma. They show a more aggressive biological behaviour than conventional carcinoids. We report a case of a 64-years-old female patient with a diffuse infiltration of the appendicular wall by an adenocarcinoid. Due to the positive surgical margin and the tumor expansion a hemicolectomy was performed. There are no precise criteria to direct the operative choice between appendectomy and hemicolectomy. It is thought that appendectomy is sufficient in case of small tumors in the tip of the appendix. Patients with diffuse appendicular involvement require a more aggressive surgical therapy.