Demonstration of free radical generation in the "stunned" myocardium in the conscious dog and identification of major differences between conscious and open-chest dogs.

Abstract

IntroductionConscious dogs undergoing a 15-min coronary occlusion were given a-phenyl N-tert-butyl nitrone (PBN) and the local coronary venous plasma was analyzed by electron paramagnetic resonance spectroscopy. A prolonged myocardial release of PBN radical adducts was observed, which exhibited a burst in the initial minutes of reflow (peaking at 3 min) and then abated but continued for 1-3 h after reperfusion. Recent studies using spin trapping techniques ( 1-7) support the hypothesis that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial "stunning" [8]). These studies have shown that free radicals are generated in various animal models ofstunned myocardium ( 1, 2, 7), and that the generation ofthe radicals is inhibited by the same antioxidants that attenuate postischemic dysfunction (3-7).

Attenuation of ischemic preconditioning in pigs by scavenging of free oxyradicals with ascorbic acid

“…In anesthetized dogs (31) and in the present study, the ascorbyl radical was detectable already under baseline conditions, which suggests a basal free radical production that might be favored by the open-chest preparation (16). Additionally, due to a rate constant for ascorbic acid to scavenge free oxyradicals that is some magnitudes higher than the rate constant for the dismutation of the ascorbyl radical (8), an accumulation of the ascorbyl radical may occur, and the concentration of free oxyradicals at baseline may be overestimated.…”

Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning

“…33,38,39 At the time of this writing, at least 22 full-length articles have been published that have examined the effect of antioxidants on myocardial stunning after a 15-minute coronary occlusion; all of these articles (except those that used superoxide dismutase alone [40][41][42] or catalase alone 40 ) have reported a protective effect of antioxidants against stunning. 37 Furthermore, generation of ROS in stunned myocardium has been demonstrated directly by both spin trapping 9,39,[43][44][45][46][47] and aromatic hydroxylation 48 techniques, and attenuation of ROS generation has repeatedly been shown to result in attenuation of contractile dysfunction. 9,39,43,45,46 A role of ROS in the genesis of myocardial stunning can now be regarded as a proven hypothesis.…”

Generation of Free Radicals and the Damage Done to the Sarcoplasmic Reticulum During Reperfusion Injury Following Brief Ischemia in the Canine Heart

“…28 On these grounds, we considered that our carbon-centered radicals were endogenous radicals. Li et al detected 2 carbon-centered radicals in the stunned myocardium in a conscious canine model (aH = 0.60 mT, aN = 1.52 mT; aH = 0.30 mT, aN = 1.46 mT), 29 and the hyperfine coupling constants of one of them was similar, but not identical, to our simulated signal A. Dissimilarities in animal models, experimental protocol, and PBN adduct extraction procedures (Blight-Dyer method in the present study) may explain these differences. Because the full chemical nature of the trapped radicals was not reported in the previous study, we could not identify our observed free radicals, and because these adducts were soluble in nonaqueous solvents, they may have been secondary radicals derived from the membrane lipids of the myocardium or endothelium.…”