The endotoxin-induced contractile dysfunction in the guinea pig heart is
not mediated by nitric oxide..
Decking, Ulrich K. M., Christian W. Flesche, Axel Gvdecke, and Jurgen
Schrader.
Institut f|r Herz- und Kreislaufphysiologie, Institut f|r Klinische
Anaesthesiologie, Heinrich-Heine-Universitdt D|sseldorf, D-40225 D|sseldorf,
Germany
APStracts 2:0008H, 1995.
The decreased contraction amplitude of isolated cardiac myocytes from guinea
pigs exposed to lipopolysaccharide (LPS) was reported to be partially
reversed by L-NAME, an inhibitor of nitric oxide (NO) synthase (Am.J.Physiol.
263: H1963, 1992). We have tested the potential involvement of NO-formation
in LPS-induced cardiac depression in the intact heart. Isolated hearts of
LPS-treated (4mg/kg i.p., 4h prior to organ removal) and control guinea pigs
were perfused either in the constant volume or constant pressure mode. Left
ventricular pressure (LVP) of LPS-hearts (n=6) was greatly decreased in
comparison to untreated controls (n=6) (48111 vs. 93118 mmHg), while heart
rate (213127 vs. 228131 min-1) and coronary flow (5.511 vs. 6.712.1 ml*min-1)
were not significantly different. Perfusion of LPS-hearts with L-NMMA or L
-NAME (100 5M each) at constant flow (9 ml/min) did not increase LVP (50114
and 44111 mmHg, respectively, vs. 52114 mmHg). However, coronary resistance
increased significantly. Similar results were obtained in the untreated
control group. There was no difference between LPS- and control hearts in
venous adenosine release (104158 vs.133186 pmol*min-1*g-1). Measurement of
the activities of the induced (iNOS) and constitutive form of NO-synthase
(citrulline assay) revealed that there was no difference in total NOS
-activity between LPS- and control hearts (237182 vs. 181197 fmol*min-1*(mg
protein)-1). There was no measurable induction of iNOS in the LPS-hearts
excised 4 hours after LPS treatment either. Finally, cardiac energy status
was studied by 31P NMR spectroscopy (n=4 in each group). There was no
difference between LPS- and control hearts in myocardial ATP (5.210.6 vs.
5.611.2 mM), PCr (11.111.3 vs. 12.112.4 mM), pH and calculated free ADP
(59120 vs. 50127 5M). It is concluded that the LPS-induced depression of
contractile force in guinea pig hearts is neither due to an increased NO
formation nor to an impaired cardiac energy metabolism.
Received 1 August 1994; accepted in final form 11 January, 1995.
APS Manuscript Number H678-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.