Role of Reactive Oxygen Species in the Sensitivity of Rat Hypertrophied Myocardium to Ischemia

E. I. Kalenikova^1*, E. A. Gorodetskaya¹, A. N. Murashev², E. K. Ruuge³, and O. S. Medvedev¹

¹Faculty of Medicine, Lomonosov Moscow State University, Lomonosovsky pr. 31/5, Moscow 117192, Russia; fax: (7-095) 939-2423; E-mail: eikaleni@fbm.msu.ru

²Branch of Shemyakin and Ovchinnikov Institute of Organic Chemistry, ul. Institutskaya 6, Pushchino 142290, Moscow Region, Russia; fax: (0967) 79-0527; E-mail: murashev@fibkh.serpukhov.su

³Institute of Experimental Cardiology, Cardiology Research Center, 3-ya Cherepkovskaya ul. 15a, Moscow 121552, Russia; fax: (7-095) 414-6699; E-mail: ruuge@bior.phys.msu.su

^* To whom correspondence should be addressed.

Received May 15, 2003; Revision received June 24, 2003

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The relationship between hydroxyl radical (OH^·) generation in the zone of ischemia/reperfusion and the size of infarction formed was investigated in 18-22-week-old anaesthetized male SHRSP and Wistar rats using a myocardial microdialysis technique. The marker of OH^· generation, 2,3-dihydroxybenzoic acid (2,3-DHBA), was analyzed in dialyzates by high performance liquid chromatography with electrochemical detection. Myocardial ischemia was induced by ligation of the descending branch of the left main coronary artery for 30 min. The mean value of basal 2,3-DHBA level in the dialyzate samples from SHRSP (243 ± 21 pg for 30 min) was significantly higher than that from Wistar rats (91 ± 4 pg for 30 min, p < 0.0002); it positively correlated with left ventricular hypertrophy (r = 0.806; p < 0.05). During reperfusion total 2,3-DHBA output was 1.8-fold higher in SHRSP than in Wistar rats (659 ± 60 pg versus 364 ± 66 pg for 60 min, respectively, p < 0.0002). At the same time, 2,3-DHBA increase above the basal level was the same in Wistar and SHRSP rats (181 ± 25 and 172 ± 36 pg for 60 min, respectively). The infarct size in SHRSP (45.4 ± 4.3%) was significantly higher (p < 0.05) than in Wistar rats (32.8 ± 3.3%). There was a significant positive correlation between basal level of 2,3-DHBA and total reperfusion 2,3-DHBA content in SHRSP (r = 0.752; p < 0.05). Thus, data obtained clearly indicate that the hypertrophied myocardium of SHRSP was less tolerant to ischemia/reperfusion than that of Wistar rats due to chronically increased OH^· production and enhanced total OH^· output during reperfusion. Greater myocardial damage in SHRSP than in Wistar rats following the equal increase in OH^· production above the basal level suggests the existence of deficit of the antioxidant defense in the hypertrophied myocardium.

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KEY WORDS: oxidative stress, hydroxyl radical, myocardial hypertrophy, myocardial ischemia, microdialysis, high-performance liquid chromatography, salicylate

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