Effect of SOD-1 over-expression on myocardial function during resuscitated murine septic shock.
OBJECTIVE
To test the hypothesis whether genetic over-expression of the Cu/Zn-superoxide dismutase (SOD-1) prevents the sepsis-related impairment of myocardial function and norepinephrine responsiveness in a resuscitated murine model of septic shock.


METHODS
Fifteen hours after cecal ligation and puncture or sham-operation wild type, heterozygous and homozygous SOD-1 over-expressing mice were anesthetized, ventilated and instrumented with central venous and left ventricular pressure-conductance catheters, to assess heart function at 18, 21, and 24 h after CLP or sham-operation. Hydroxyethylstarch and noradrenaline (in the CLP-mice only) were infused to maintain normotensive hemodynamics.


RESULTS
Fluid resuscitation and noradrenaline requirements did not differ between the mouse strains. While total myocardial SOD activity was five- and ninefold higher in the heterozygous and homozygous over-expressing animals, respectively, tissue catalase activity was not different. Anesthesia and fluid resuscitation alone caused left ventricular dilatation and a progressive fall in left ventricular end-systolic pressure and maximal systolic contraction (dp/dt (max)), while stroke volume and cardiac output increased. Due to the noradrenaline infusion heart rate, end-systolic pressure as well as dp/dt (max) and dp/dt (max) were significantly higher and relaxation time significantly lower in the CLP-mice, again without difference between the genetic strains.


CONCLUSIONS
We conclude that neither hetero- nor homozygous SOD-1 over-expression caused a sustained improvement of the sepsis-related impairment of myocardial norepinephrine responsiveness, possibly due to the lacking increase of the tissue catalase and the mitochondrial SOD activity as well as the ongoing i.v. noradrenaline.
Baumgart
Katja
K
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Parkstrasse 11, 89073, Ulm, Germany. katja.baumgart@web.de
Simkova
Vladislava
V
Wagner
Florian
F
Weber
Sandra
S
Georgieff
Michael
M
Radermacher
Peter
P
Albuszies
Gerd
G
Barth
Eberhard
E
D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology; D010084:Oxidation-Reduction; D012772:Shock, Septic / Q000503:physiopathology / Q000628:therapy*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D009638:Norepinephrine