METHIONINE IN PROTECTION OF HEMORRHAGIC-SHOCK - ROLE OF OXYGEN FREE-RADICALS AND HYPOCHLOROUS ACID

Various mechanisms may exist for activation of polymorphonuclear (PMN) leukocytes during hemorrhagic shock and reinfusion. During activation of PMN leukocytes, hypochlorous acid (HOCl) is produced in addition t o oxygen free radicals. We studied the effects of hemorrhagic shock an d reinfusion on cardiac function and contractility, oxygen free radica l producing activity of PMN leukocytes (PMN chemiluminescence), and se rum and cardiac tissue malondialdehyde (MDA), a lipid peroxidation pro duct, with and without methionine (quencher of hypochlorous acid) in a nesthetized dogs, in order to assess the role of hypochlorous acid in depression of cardiac function and contractility in hemorrhagic shock. The dogs were divided into two groups: group I, hemorrhagic shock (2 hr) followed by reinfusion (2 hr); and group II, hemorrhagic shock and reinfusion similar to group I but methionine (30 mg/kg i.v.) was admi nistered before bleeding, before reinfusion, and after 1 hr of reinfus ion in this group. Mean arterial pressure (mAo), mean pulmonary arteri al pressure (mPAP), index of myocardial contractility (dp/dt(max)), an d cardiac function (stroke volume index [SVI], left-ventricular work i ndex [LVWI]) decreased significantly during shock and the decreases we re similar in both groups. The indices of myocardial contractility whi ch are independent of pre- and/or afterload ([dp/dt]/IIP and [dp/dt]/I IP/CPIP) were affected to a lesser degree than the other indices of my ocardial contractility (dp/dt(max)) during shock and reinfusion. Howev er, the systemic and pulmonary vascular resistance increased significa ntly in both groups. Postinfusion recovery of cardiac function and con tractility in group II was greater than in group I. Cardiac function a nd contractility after reinfusion returned to preshock levels initiall y followed by a decrease below the preshock values in group I. However , these parameters remained at or above preshock levels after reinfusi on in group II. Cardiac tissue MDA levels were higher in group I, as c ompared to those in control dogs. The tissue levels of MDA in group II were lower than in group I but similar to those of control. The serum MDA did not change significantly during shock and reinfusion in eithe r group. Although there were increases in the serum MDA after reinfusi on in group I, they were not significant. While the chemiluminescent a ctivity of PMN leukocyte increased significantly in group I, this acti vity decreased significantly in group II during shock and reinfusion. Methionine in in vitro studies did not affect the oxygen free radical producing activity of PMN leukocyte. These results suggest that hypoch lorous acid is produced during shock and reinfusion. The decrease in t he cardiac function and contractility after reinfusion may be due to h ypochlorous acid.