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 to oxygen free radicals. We studied the effects of hemorrhagic shock and reinfusion on cardiac function and contractility, oxygen free radical producing activity of PMN leukocytes (PMN chemiluminescence), and serum and cardiac tissue malondialdehyde (MDA), a lipid peroxidation product, with and without methionine (quencher of hypochlorous acid) in anesthetized 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 administered before bleeding, before reinfusion, and after 1 hr of reinfusion in this group. Mean arterial pressure (mAo), mean pulmonary arterial pressure (mPAP), index of myocardial contractility (dp/dtmax), and cardiac function (stroke volume index [SVI], left-ventricular work index [LVWI]) decreased significantly during shock and the decreases were similar in both groups. The indices of myocardial contractility which are independent of pre- and/or afterload ([dp/dt]/IIP and [dp/dt]/IIP/CPIP) were affected to a lesser degree than the other indices of myocardial contractility (dp/dtmax) during shock and reinfusion. However, the systemic and pulmonary vascular resistance increased significantly in both groups. Postinfusion recovery of cardiac function and contractility in group II was greater than in group I. Cardiac function and contractility after reinfusion returned to preshock levels initially followed by a decrease below the preshock values in group I. However, these parameters remained at or above preshock levels after reinfusion in group II. Cardiac tissue MDA levels were higher in group I, as compared 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 either group. Although there were increases in the serum MDA after reinfusion in group I, they were not significant. While the chemiluminescent activity of PMN leukocyte increased significantly in group I, this activity 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 hypochlorous acid is produced during shock and reinfusion. The decrease in the cardiac function and contractility after reinfusion may be due to hypochlorous acid.
Prasad
K
K
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Kapoor
R
R
Kalra
J
J
D000818:Animals; D004285:Dogs; D005609:Free Radicals; D006439:Hemodynamics; D006997:Hypochlorous Acid / Q000378:metabolism*; D007958:Leukocyte Count; D008315:Malondialdehyde / Q000378:metabolism*; D008715:Methionine / Q000494:pharmacology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000378:metabolism*
D005609:Free Radicals; D008315:Malondialdehyde; D006997:Hypochlorous Acid; D008715:Methionine; D010100:Oxygen