Alterations in cardiac hemodynamics following endotoxin are not due to reduced myocardial contractility
© Jianhui et al; licensee BioMed Central Ltd. 2008
Published: 18 November 2008
Impaired cardiac function due to reduced myocardial contractility is a typical manifestation of septic shock, whose mechanisms are poorly defined. Experimentally, the administration of endotoxin (lipopolysaccharide (LPS)) to laboratory animals is classically used to study the mechanisms of septic cardiomyopathy. However, most studies evaluating the effects of LPS on the heart in vivo have relied on indirect, load-dependent, indices of cardiac function, and thus could not precisely determine the real consequences of LPS on cardiac contractility. We therefore evaluated the direct effects of LPS on cardiac contractility in mice, using left ventricular (LV) micro-tip pressure–volume (PV) catheters, which provide load-independent measurements of cardiac function, including end-systolic elastance (Ees) and maximal elastance (Emax).
Male BALB/c mice received an intraperitoneal injection of Escherichia coli LPS (1, 5, 10, or 20 mg/kg). After 2, 6 or 20 hours, selected groups of mice were anesthetized, intubated and mechanically ventilated. A PV catheter was inserted into the left ventricle through the right carotid artery. LV pressure (end systolic (LVSP) and end-diastolic (LVDP)) and volumes (end systolic (ESV) and end-diastolic (EDV)) were recorded, allowing the calculation of the stroke volume, stroke work, cardiac output and ejection fraction. Ees and Emax were computed from the slope of the end-systolic PV relationships of successive PV loops obtained at rapidly reduced preload, by inferior vena cava compression. Mice were sacrificed at the end of the experiments.
EDV decreased with LPS, mostly after 6 hours, whereas ESV did not change. LVSP was slightly decreased only after 6 hours, and LVDP was not significantly influenced by LPS. The stroke volume, stroke work, ejection fraction and dp/dtmax were reduced at all doses of LPS, mostly after 6 hours and slightly recovered after 20 hours. In spite of an increase in heart rate, the cardiac output decreased, especially after 6 hours and at the high doses (10 and 20 mg/kg) of LPS. Most importantly, both Ees and Emax markedly increased after all doses of LPS, mostly after 2 and 6 hours, and returned back to control values after 20 hours.
In striking contrast with the usual belief, LPS does not induce direct negative inotropic effects in the mouse, but instead markedly enhances contractility. The alterations in cardiac function induced by LPS are only, and entirely, due to altered loading conditions, which are mainly observed 6 hours after the injection of LPS.
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