Matthias Behrends1, Jürgen Peters. 1. Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. matthias.behrends@uni-essen.de
Abstract
OBJECTIVE: Sepsis-evoked myocardial dysfunction is possibly due to decreased myofilament calcium sensitivity, and a calcium sensitizer may thus specifically improve contractility in sepsis by enhancing myofilament calcium sensitivity. We examined whether the calcium sensitizer levosimendan mitigates myocardial dysfunction and improves contractility in hearts isolated from endotoxin-treated guinea pigs. DESIGN AND SETTING: Prospective, controlled, randomized animal study in a university research laboratory. SUBJECTS: Guinea pig hearts isolated 4 h (n=10) or 18 h (n=8) following E. coli LPS (4 mg/kg i.p.) and hearts from sham-treated controls (n=11 and n=6). INTERVENTIONS: Isolated hearts were perfused at constant aortic pressure [Krebs-Henseleit buffer, heart rate: 300/min, left ventricular (LV) diastolic pressure: 6-8 mmHg], and LV developed pressure (LVd P) and LVd P/d t were continuously assessed. Levosimendan was added to the perfusate in incremental concentrations (0.03, 0.1, 0.3 microM). MEASUREMENTS AND RESULTS: Endotoxin resulted in a significant decrease in LVd P by 20+/-6% and 43+/-8%, in +LVd P/d t by 16+/-5% and 44+/-7%, and in -LVd P/d t by 27+/-8% and 47+/-8% after 4 and 18 h, respectively. In septic hearts levosimendan increased LV function concentration-dependently by 32+/-4% (LVd P), 33+/-5% (+LVd P/d t), and 37+/-7% (-LVd P/d t) 4 h and by 31+/-6% (LVd P), 33+/-6% (+LVd P/d t), and 32+/-7% (-LVd P/d t) 18 h after LPS. However, levosimendan increased myocardial function similarly in control hearts. CONCLUSIONS: While the calcium sensitizer levosimendan markedly improved LV contractility in hearts from both endotoxic and sham animals, it failed to specifically abolish endotoxin-evoked myocardial dysfunction. Thus, decreased calcium sensitivity either does not play a major role in endotoxin-evoked cardiomyopathy or the location of its pathomechanism differs from levosimendan's site of action.
OBJECTIVE:Sepsis-evoked myocardial dysfunction is possibly due to decreased myofilament calcium sensitivity, and a calcium sensitizer may thus specifically improve contractility in sepsis by enhancing myofilament calcium sensitivity. We examined whether the calcium sensitizer levosimendan mitigates myocardial dysfunction and improves contractility in hearts isolated from endotoxin-treated guinea pigs. DESIGN AND SETTING: Prospective, controlled, randomized animal study in a university research laboratory. SUBJECTS:Guinea pig hearts isolated 4 h (n=10) or 18 h (n=8) following E. coli LPS (4 mg/kg i.p.) and hearts from sham-treated controls (n=11 and n=6). INTERVENTIONS: Isolated hearts were perfused at constant aortic pressure [Krebs-Henseleit buffer, heart rate: 300/min, left ventricular (LV) diastolic pressure: 6-8 mmHg], and LV developed pressure (LVd P) and LVd P/d t were continuously assessed. Levosimendan was added to the perfusate in incremental concentrations (0.03, 0.1, 0.3 microM). MEASUREMENTS AND RESULTS: Endotoxin resulted in a significant decrease in LVd P by 20+/-6% and 43+/-8%, in +LVd P/d t by 16+/-5% and 44+/-7%, and in -LVd P/d t by 27+/-8% and 47+/-8% after 4 and 18 h, respectively. In septic hearts levosimendan increased LV function concentration-dependently by 32+/-4% (LVd P), 33+/-5% (+LVd P/d t), and 37+/-7% (-LVd P/d t) 4 h and by 31+/-6% (LVd P), 33+/-6% (+LVd P/d t), and 32+/-7% (-LVd P/d t) 18 h after LPS. However, levosimendan increased myocardial function similarly in control hearts. CONCLUSIONS: While the calcium sensitizer levosimendan markedly improved LV contractility in hearts from both endotoxic and sham animals, it failed to specifically abolish endotoxin-evoked myocardial dysfunction. Thus, decreased calcium sensitivity either does not play a major role in endotoxin-evoked cardiomyopathy or the location of its pathomechanism differs from levosimendan's site of action.
Authors: Edward Abraham; Peter Andrews; Massimo Antonelli; Laurent Brochard; Christian Brun-Buisson; Geoffrey Dobb; Jean-Yves Fagon; Johan Groeneveld; Jordi Mancebo; Philipp Metnitz; Stefano Nava; Michael Pinsky; Peter Radermacher; Marco Ranieri; Christian Richard; Robert Tasker; Benoit Vallet Journal: Intensive Care Med Date: 2004-06-26 Impact factor: 17.440
Authors: Mads D Vildbrad; Asger Andersen; Sarah Holmboe; Steffen Ringgaard; Jan M Nielsen; Jens Erik Nielsen-Kudsk Journal: Pulm Circ Date: 2014-09 Impact factor: 3.017
Authors: Patrick Scheiermann; Devan Ahluwalia; Sandra Hoegl; Andrea Dolfen; Marc Revermann; Bernhard Zwissler; Heiko Muhl; Kim A Boost; Christian Hofstetter Journal: Intensive Care Med Date: 2009-04-15 Impact factor: 17.440