TY - JOUR
T1 - Use of spin traps in intact animals undergoing myocardial ischemia/reperfusion
T2 - A new approach to assessing the role of oxygen radicals in myocardial "stunning"
AU - Bolli, Roberto
AU - Mccay, Paul B.
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid 88R-171 from the American Heart Association, Texas Affiliate, NIH Grant GM365 12. Biomedical Research Support Grant 2507RR05538-25, NHLBI Grants HL36277 and HL43151. and by the SCOR in Heart Failure Grant HL42267 from NIH. R.B. was a recipient of the Physician-Scientist Award of the American College of Chest Physicians.
PY - 1990
Y1 - 1990
N2 - Numerous studies have indirectly, suggested that oxygen-derived free radicals play an important path-ogenetic role in the prolonged depression of contractile function observed in myocardium reperfused after reversible ischemia (myocardial "stunning" In order to provide direct evidence for the oxy-radical hypothesis of stunning, we administered the spin trap, αphenyl N-tert-butyl nitrone (PBN), to open-chest dogs undergoing a 15-min coronary artery occlusion followed by reperfusion. Plasma of local coronary venous blood was analyzed by electron paramagnetic resonance (EPR) spectroscopy. EPR signals characteristic of radical adducts of PBN appeared during ischemia and increased dramatically in the first few minutes after reperfusion. After this initial burst, the production of adducts abated but did not cease, persisting up to 3 h after reflow. The production of PBN adducts after reperfusion was inversely related to collateral flow during ischemia. PBN itself enhanced recovery of contractile function. indicating that the radicals trapped may play a pathogenetic role in myocardial stunning. Superoxide dismutase plus catalase attenuated PBN adduct production and, at the same time, improved recovery of contractile function. Antioxidant therapy given 1 min before reperfusion suppressed PBN adduct production and improved contractile recovery; however, the same therapy given 1 min after reperfusion did not suppress early radical production and did not attenuate contractile dysfunction. After i.v. administration, the elimination half-life of PBN was estimated to be approximately 4-5 h. The results demonstrate that 1) free radicals are produced in the stunned myocardium in intact animals; 2) inhibition of free radical production results in improved contractile recovery; and 3) the free radicals important in causing dysfunction are produced in the first few minutes of reperfusion. Taken together, these studies provide cogent evidence supporting the oxy-radical hypothesis of stunning in open-chest dogs. It is now critical to determine whether these results can be reproduced in conscious animal preparations.
AB - Numerous studies have indirectly, suggested that oxygen-derived free radicals play an important path-ogenetic role in the prolonged depression of contractile function observed in myocardium reperfused after reversible ischemia (myocardial "stunning" In order to provide direct evidence for the oxy-radical hypothesis of stunning, we administered the spin trap, αphenyl N-tert-butyl nitrone (PBN), to open-chest dogs undergoing a 15-min coronary artery occlusion followed by reperfusion. Plasma of local coronary venous blood was analyzed by electron paramagnetic resonance (EPR) spectroscopy. EPR signals characteristic of radical adducts of PBN appeared during ischemia and increased dramatically in the first few minutes after reperfusion. After this initial burst, the production of adducts abated but did not cease, persisting up to 3 h after reflow. The production of PBN adducts after reperfusion was inversely related to collateral flow during ischemia. PBN itself enhanced recovery of contractile function. indicating that the radicals trapped may play a pathogenetic role in myocardial stunning. Superoxide dismutase plus catalase attenuated PBN adduct production and, at the same time, improved recovery of contractile function. Antioxidant therapy given 1 min before reperfusion suppressed PBN adduct production and improved contractile recovery; however, the same therapy given 1 min after reperfusion did not suppress early radical production and did not attenuate contractile dysfunction. After i.v. administration, the elimination half-life of PBN was estimated to be approximately 4-5 h. The results demonstrate that 1) free radicals are produced in the stunned myocardium in intact animals; 2) inhibition of free radical production results in improved contractile recovery; and 3) the free radicals important in causing dysfunction are produced in the first few minutes of reperfusion. Taken together, these studies provide cogent evidence supporting the oxy-radical hypothesis of stunning in open-chest dogs. It is now critical to determine whether these results can be reproduced in conscious animal preparations.
KW - Coronary artery reperfusion
KW - Electron paramagnetic resonance spectroscopy
KW - Free oxygen radicals
KW - Myocardial dysfunction
KW - Spin traps
KW - αphenyl N-tert-butyl nitrone
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U2 - 10.3109/10715769009145674
DO - 10.3109/10715769009145674
M3 - Article
C2 - 2167254
AN - SCOPUS:0025053056
SN - 1071-5762
VL - 9
SP - 169
EP - 180
JO - Free Radical Research
JF - Free Radical Research
IS - 3-6
ER -