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.
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Parkstrasse 11, 89073, Ulm, Germany. katja.baumgart@web.de
Katja
K
Baumgart
Vladislava
V
Simkova
Florian
F
Wagner
Sandra
S
Weber
Michael
M
Georgieff
Peter
P
Radermacher
Gerd
G
Albuszies
Eberhard
E
Barth
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