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BASIC SCIENCE

Potent antifibrillatory effects of intrapericardial nitroglycerin in the ischemic porcine heart

Kapil Kumar, MD^*, Khanh Nguyen, BA, Sergio Waxman, MD^*, Bruce D. Nearing, PhD^*, Gregory A. Wellenius, MSc, Susan X. Zhao, MS^* and Richard L. Verrier, PhD, FACC^*,*

^* Harvard Medical School, Boston, Massachusetts, USA
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Harvard School of Public Health, Boston, Massachusetts, USA

Manuscript received August 23, 2002; revised manuscript received December 19, 2002, accepted January 16, 2003.

^* Reprint requests and correspondence: Dr. Richard L. Verrier, Beth Israel Deaconess Medical Center, One Autumn Street, Kennedy Building, 5th Floor, Boston, Massachusetts 02215, USA.
rverrier{at}bidmc.harvard.edu

OBJECTIVES: We investigated the antiarrhythmic effects of intrapericardial nitroglycerin (NTG) during acute myocardial ischemia in the porcine heart.

BACKGROUND: Nitroglycerin is a nitric oxide donor that exerts potent effects on the cardiovascular system. Intrapericardial administration allows investigation of pharmacologic actions on cardiac tissue in an in vivo system while minimizing the confounding influences of systemic effects.

METHODS: In 29 closed-chest pigs, myocardial ischemia was induced by intraluminal balloon occlusion of the left anterior descending coronary artery. Arrhythmia incidence was monitored during 5-min balloon inflations performed without drug and at 15, 45, 75, and 105 min after NTG (4,000 µg bolus) administered by percutaneous transatrial access into the pericardial space. Electrocardiograms were monitored for ischemia-induced T-wave alternans (TWA), a marker of electrical instability. The antiadrenergic potential of NTG was investigated by examining the drug’s suppression of dobutamine-induced increase in myocardial contractility.

RESULTS: Control coronary artery occlusion provoked ventricular fibrillation (VF) in all animals. Intrapericardial NTG suppressed VF at 45 min in all six pigs (p < 0.05) and reduced TWA across a parallel time course (from 459.1 ± 144.4 µV before drug to 42.22 ± 13.96 µV at 45 min, p = 0.047). The antifibrillatory effect occurred as early as 15 min and persisted for up to 75 min. Augmentation of maximum of the first time derivative of left ventricular pressure by dobutamine was blunted by intrapericardial NTG (from 3,999 ± 196 mm Hg/s before NTG to 3,543 ± 220 mm Hg/s at 15 min, p = 0.012).

CONCLUSIONS: Intrapericardial NTG exerts a robust antifibrillatory action. Potential mechanisms include reduction in electrical instability and blunting of adrenergic effects.

Abbreviations and Acronyms   cGMP   cyclic guanine monophosphate   ECG   electrocardiogram   HR   heart rate   LAD   left anterior descending coronary artery   LV   left ventricle/ventricular   LV dP/dt max   maximum of the first time derivative of left ventricular pressure   NO   nitric oxide   NTG   nitroglycerin   SBP   systolic blood pressure   TWA   T-wave alternans   VF   ventricular fibrillation   VPB   ventricular premature beat

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