Relationship Between Redox State of Whole Arterial Blood Glutathione and Left Ventricular Function After Acute Myocardial Infarction

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1 J Cardiol 2004 Oct; 44 4 : Relationship Between Redox State of Whole Arterial Blood Glutathione and Left Ventricular Function After Acute Myocardial Infarction Miyuki Rie Yukihiro Osamu Hiroshi Takeshi Takaaki Kazuyuki OHSAWA, MD TSURU, MD HOJO, MD MIZUNO, MD FUKAZAWA, MD MITSUHASHI, MD KATSUKI, MD SHIMADA, MD, Abstract Objectives. To investigate the role of oxidative stress in left ventricular function after acute myocardial infarction. Methods. We studied 41 patients with acute myocardial infarction 30 men and 11 women, mean age years with Thrombolysis in Myocardial Infarction grade 3 recanalization of occluded coronary arteries within 12 hr after onset. Cardiac catheterization was performed at the time of admission and before discharge. Three markers for oxidative stress were measured : plasma lipid hydroperoxide, plasma creatol and whole arterial blood glutathione at the time of admission. Results. Mean time from onset to recanalization was hr. The patients were divided into two groups according to the changes in left ventricular wall motion LVWM ; patients who showed improvement in LVWM and those without improvement. There were no significant differences in age, sex, coronary risk factors, severity of coronary artery disease, time from onset to recanalization or ejection fraction between two groups. Maximum creatine kinase and C-reactive protein levels in patients without LVWM improvement were significantly higher than in patients with improvement. Plasma levels of lipid hydroperoxide and creatol did not differ significantly between two groups. On the other hand, reduced glutathione/oxidized glutathione ratio in arterial blood in patients without LVWM improvement was significantly lower than in patients with LVWM improvement vs , p Conclusions. Our results suggest that whole arterial blood glutathione is more oxidized in acute myocardial infarction patients without LVWM improvement than in patients with improvement. Redox state of arterial blood can be a predicting factor for left ventricular function after acute myocardial infarction. J Cardiol 2004 Oct; 44 4 : Key Words Myocardial infarction, pathophysiology Infarct size Ischemia Ventricular function : Department of Cardiology, Jichi Medical School, Tochigi Address for correspondence : HOJO Y, MD, Department of Cardiology, Jichi Medical School, Yakushiji , Minamikawachi, Kawachi-gun, Tochigi Manuscript received April 16, 2004; revised July 22, 2004; accepted July 23,

2 142 reactive oxygen species ,9 mm SH oxidized glutathione : GSSG reducted glutathione : GSH GSH/GSSG Fig. 1 1/ Fig. 1 Glutathione system Glutathione, a tripeptide -glutamylcysteinylglycine, is a major cellular antioxidant. Reduced glutathione GSH provides protons for glutathione peroxidase which catalyzes hydrogen peroxide to water. During this process, GSH becomes oxidized glutathione GSSG. GSSG is reduced by glutathione reductase and nicotinamide adenine dinucleotide phosphate NADPH. When cells are exposed to oxidative stress, the ratio of GSH/GSSG decreases as a consequence of GSSG accumulation. Thrombolysis in Myocardial Infarction TIMI 3 12TIMI 3 2 Na-EDTA 7 8,9 GSH/GSSG GSH/GSSG Oxis Research QLV-CMS, MEDIS 3 2 Student t 2 p 0.05 J Cardiol 2004 Oct; 44 4 :

3 143 Table 1 Clinical parameters in patients with acute myocardial infarction Age yr Sex male/female Coronary risk factors Hypertension Diabetes mellitus Hyperlipidemia Smoking Family history of coronary artery disease Infarction site Anterior/inferior/lateral Number of diseased vessels 0/1/2/3 Time until recanalization hr Left ventricular ejection fraction % Maximum creatine kinase IU/l Maximum C-reactive protein mg/dl Improvement group n / /9/4 2/14/4/ , No improvement group n / /5/1 0/5/11/ , Continuous values are mean SEM. : %. p , IU/l % % TIMI TIMI % Table 1 2 2, vs 1, IU/l p 0.05 C vs mg/dl p GSH/GSSG vs p 0.05 Table 2 J Cardiol 2004 Oct; 44 4 :

4 144 Table 2 Markers for oxidative stress in patients with acute myocardial infarction Serum lipid peroxide nmol/l Serum creatol g/dl Total glutathione mol/g protein GSH mol/g protein GSSG mol/g protein GSH/GSSG ratio Values are mean SEM. p Abbreviations as in Fig. 1. Improvement group No improvement group GSH/GSSG 1/1,000 M GSH/GSSG GSH/GSSG C Src 12,13 14 S=S SH N- 15,16 Arstall 17 N- N- mm J Cardiol 2004 Oct; 44 4 :

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