This Article Abstract Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Flesch, M. Articles by Böhm, M. Search for Related Content PubMed PubMed Citation Articles by Flesch, M. Articles by Böhm, M.

Effects of endotoxin on human myocardial contractility involvement of nitric oxide and peroxynitrite

Markus Flesch, MD^a, Heiko Kilter, MD^a, Bodo Cremers, MS^a, Ulrich Laufs, MD^a, Michael Südkamp, MD^*, Monika Ortmann, MD, Frank U. Müller, MD and Michael Böhm, MD^a

^a Klinik III für Innere Medizin, der Westfälischen Wilhelms-Universität, Münster, Germany
^* Klinik für Herz- und Thoraxchirurgie, der Westfälischen Wilhelms-Universität, Münster, Germany
Pathologisches Institut, der Universität zu Köln, der Westfälischen Wilhelms-Universität, Münster, Germany
Institut für Pharmakologie und Toxikologie, der Westfälischen Wilhelms-Universität, Münster, Germany

View larger version (30K): [in a new window]   Figure 1 Effect of treatment of isolated human left ventricular myocardial preparations from terminally failing hearts with lipopolysaccharides (Endo, 1 µg/ml) on the concentration-dependent inotropic response to isoprenaline. Upper panel shows the effect of 6 h and lower panel the effect of 12 h of incubation. Also, the effects of co-incubation of isolated myocardial preparations with either L-NMMA (100 µmol/liter) or hemoglobin (Hb, 2 µg/ml) are demonstrated. Ordinate gives force of contraction in mN, abscissa concentration of isoprenaline in µmol/liter. Data are given as mean ± SEM.

View larger version (18K): [in a new window]   Figure 2 Comparison of the effect of lipopolysaccharide treatment for 12 h on the concentration-dependent inotropic response of failing and nonfailing left ventricular myocardial preparations to isoprenaline. (A) This shows the inotropic response to isoprenaline after incubation of myocardial preparations in normal tyrode (control); (B) shows the inotropic response to isoprenaline after incubation in tyrode supplemented with lipopolysaccharides (Endo, 1 µg/ml). Data are given as mean ± SEM.

View larger version (47K): [in a new window]   Figure 3 Result of iNOS mRNA detection by RT-PCR in left ventricular myocardial preparations from two nonfailing hearts incubated for 12 h either in normal tyrode solution (control) or in tyrode plus lipopolysaccharides (1 µg/ml). Amplification products of iNOS-PCR were loaded on the left side, those of GAPDH-PCR on the right side of the gel. Notice that only in two of six nonfailing hearts shown in this figure, iNOS mRNA was not already detectable in control samples, and that iNOS mRNA was detectable in all samples from failing hearts (n = 6).

View larger version (131K): [in a new window]   Figure 4 Result of iNOS mRNA detection in human myocardial preparations by in situ hybridization. Hybridized slides is shown from endotoxin-treated myocardium. Notice that the specific iNOS hybridization signal can mainly be depicted from cardiac myocytes.

View larger version (22K): [in a new window]   Figure 5 Bar graph demonstrating the effect of endotoxin treatment (Endo, 1 µg/ml, 6 and 12 h) of human ventricular myocardial preparations in the absence or presence of L-NMMA (100 µmol/liter) on myocardial cGMP content. Acute treatment of atrial trabecula with sodium nitroprusside (SNP, 100 µmol/liter) was performed as a control. Six hours of incubation: n = 6 per condition; 12 h of incubation: n = 10 per condition, atrial preparations: n = 10 per condition. Ordinate: cGMP concentration in fmol/mg wet weight. Data are given as mean ± SEM.

View larger version (31K): [in a new window]   Figure 6 Effect of co-incubation of human left ventricular myocardial preparations for 6 h either with lipopolysaccharides (1 µg/ml, n = 5), with lipopolysaccharides and the radical-scavenger Tiron (10 mmol/liter, n = 5), with Tiron (10 mmol/liter, n = 5) alone or in normal Tyrode (control, n = 5). Upper panel shows the concentration-dependent positive inotropic effect of isoprenaline. Ordinate gives force of contraction in mN, abscissa gives isoprenaline concentrations in µmol/liter. Bar graph in the lower panel summarizes the maximum isoprenaline effects on isometric force of contraction in the different groups.