The Therapeutic Effect Of SOD On Vascular Hyporeactivity In Severe Hemorrhagic Shock

1) To investigate the possible effect of SOD on resting potential (Em) of mesenteric arteriolar smooth muscle cells (ASMCs) from normal and severe hemorrhagic shock ( HS ) rats and on ASMCs Em alterations by nitric oxide in vitro;2) To observe the influence of SOD on tissue oxygen partial pressure of sprinotrapezius muscle in severe HS rats.3) To observe the effect of SOD on vascular hyporeactivity with anti-shock efficacy in severe hemorrhagic shock in vivoPart 1 Effect of SOD on ASMCs EmMethods: HS rat models were reproduced and mesenteric ASMCs wereacutely isolated using enzymatic digestion method. ASMCs were labeledwith a Em-sensitive fluorescent dye, DiBAC4(3) and the real-timefluorescent intensity alterations were monitored through a laser confocalmicroscopy. The possible effect on SOD on Em of ASMCs from normal andHS rats and on the ASMCs Em alteration induced by nitric oxide wasinvestigated.Results: SOD showed little influence on Em of ASMCs from normal rats butcould partially reduce ASMCs hyperpolarziation from HS rats. Also SODcould partially recover the membrane hyperpolarziation of ASMCs by SNAP,a putative NO donor.Part 2. Effect of SOD on tissue oxygen partial pressure of spinotrapeziusmuscles in HS ratsMethods: Twenty four healthy adult Sprague-Dawley (SD) rats weighingbetween 180g and 200g were randomly assigned to 4 groups (n=6), i.e. Shamoperation group (SOG) , shock and saline treated group (SNSG) , shock and SOD treated group (SSODG) , Shock and SOD & alkali treated group (SSAG) . The sprinotrapezius muscle preparation was carefully made according to the Gray's method. The tissue oxygen partial prussure of sprinotrapezius muscle was detected by phosphorous fluorescent probe (20mg/kg) and a PMOD2000 Oxysport ?phosphorimeter. Results1. The normal tissue oxygen partial pressure of sprinotrapezius muscle varied from33.3?.9 mmHg to 35.9?.1mmHg.2. The tissue oxygen partial pressure of sprinotrapezius muscle in shock groups was descended to about 50% of normal value soon after bleeding, then dropped to 20% of normal value 2h after shock. The value was distinct significantly to that in SOG animals (P<0.05).3. After resuscitation, the tissue oxygen partial pressure in the shock groups animals restored closely to normal level transiently.(1) 0.5h after resuscitation, the tissue oxygen partial pressure in saline treated group re-dropped to the level as in the early stage of shock, and 2h after resuscitation, the tissue oxygen partial pressure had remained in lower level.(2) The tissue oxygen partial pressure in SSODG was higher than that in SNSG group, however, the difference showed no statistical significance.(3) The tissue oxygen partial pressure maintained at a stable high level in SSAG group, which was significantly higher than that in SNSG group and wasn't apparently difference from that in SOG group.Part 3. Therapeutic effect of SOD on hemorrhagic shock ratsMethods: 28 Sprague-Dawley rats of either sex were reproduced hemorrhagic shock (HS) and randomly divided into 4 groups: SOD-treated group, NaHCO3 -treated group, SOD+NaHCO3 -treated group and N.S-treated group. The response of arterioles to norepinephrine (NE) ,the effect of dopamine on blood pressure , blood flow velocity in arteriole The mean arterial pressure (MAP) , and the survival time with in 24 hours were measured.Results: 2 h after shock, the arteriolar vasoreactivity was significantly reduced with 24-27fold increase of NE threshold concentration. After treatment with SOD, NaHCO3, SOD+NaHCO3, arteriolar vasoreactivity was restored to some extent, of which the SOD+NaHCO3 group received a most significant effect with NE threshold concentration decreased to 4.7 fold of normal level. In SOD+NaHCO3-treated group, after treatment of SOD+ NaHCO3, injection of dopamine revealed a most significant effect on increasing MAP with 1.9 times more than that in control group, and enhacement of the rat MAP mai...