Reactive oxygen species contribute to contractile dysfunction following rapid ventricular pacing in dogs.
BACKGROUND
Ventricular tachyarrhythmias may produce subsequent myocardial dysfunction through the formation of oxygen-derived free radicals. We tested the hypothesis that the antioxidant N-acetylcysteine enhances recovery of contractile function after rapid ventricular pacing.


METHODS
Barbiturate-anesthetized dogs were instrumented for measurement of systemic and coronary hemodynamics and subendocardial segment shortening (%SS). All dogs were subjected to 3 h of rapid ventricular pacing (230 beats/min) followed by a 2 h recovery period. In three groups (n=8 each), dogs received intravenous 0.9% saline or N-acetylcysteine (50 or 150 mg/kg over 60 min) in a random manner before pacing.


RESULTS
N-acetylcysteine did not affect systemic and coronary hemodynamics or alter regional myocardial contractility. Rapid ventricular pacing significantly (P<0.05) increased rate-pressure product and left ventricular end-diastolic pressure and decreased +dP/dt(max). Rapid ventricular pacing produced equivalent degrees of contractile dysfunction in dogs receiving saline or N-acetylcysteine (e.g. %SS of 14.7+/-1.8 to -3.8+/-2.7% before and during pacing in saline-pretreated dogs). Dogs receiving the 150 mg/kg dose of N-acetylcysteine demonstrated greater recovery of contractile function than those pretreated with saline or the 50 mg/kg dose (e.g. %SS of 12.3+/-1.7% compared to 7.0+/-2.0% 2 h after pacing in dogs receiving saline). No differences in systemic and coronary hemodynamics were observed between groups during recovery from pacing.


CONCLUSIONS
The results indicate that the N-acetylcysteine enhances recovery of contractile function after rapid ventricular pacing independent of alterations in systemic and coronary hemodynamics and imply that reactive oxygen species are an important component of the contractile dysfunction following rapid pacing in vivo.
Gare
Meir
M
Department of Medicine (Division of Cardiovascular Diseases), the Medical College of Wisconsin and the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53226, USA.
Mraovic
Boris
B
Kehl
Franz
F
Kersten
Judy R
JR
Warltier
David C
DC
Pagel
Paul S
PS
D000111:Acetylcysteine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D017682:Myocardial Stunning / Q000503:physiopathology; D011336:Probability; D011897:Random Allocation; D017382:Reactive Oxygen Species; D012016:Reference Values; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000111:Acetylcysteine