Potent antifibrillatory effects of intrapericardial nitroglycerin in the ischemic porcine heart.
OBJECTIVE
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 microg 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 microV before drug to 42.22 +/- 13.96 microV 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.
Kumar
Kapil
K
Harvard Medical School, Boston, Massachusetts, USA.
Nguyen
Khanh
K
Waxman
Sergio
S
Nearing
Bruce D
BD
Wellenius
Gregory A
GA
Zhao
Susan X
SX
Verrier
Richard L
RL
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology; D004562:Electrocardiography; D007267:Injections; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D005996:Nitroglycerin / Q000008:administration & dosage*; D010496:Pericardium; D013552:Swine; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D020030:Nitric Oxide Donors; D004280:Dobutamine; D005996:Nitroglycerin