title: Persistent primary coronary dilation induced by transatrial delivery of nitroglycerin into the pericardial space: a novel approach for local cardiac drug delivery.
abstract: OBJECTIVE
  We compared the effects of intrapericardial and intracoronary nitroglycerin on coronary cross-sectional area as assessed by intravascular ultrasound and demonstrated the feasibility of local cardiac drug delivery by a newly developed method to access the normal pericardial space through the right atrial appendage.
  
  
  BACKGROUND
  Studies of nitric oxide (NO) donors have suggested that their antiarrhythmic and antiproliferative properties are more effective when administered by the intrapericardial rather than intravascular route. We postulated that NO donors delivered intrapericardially would also cause sustained coronary vasodilation without significant systemic hypotension.
  
  
  METHODS
  Intrapericardial nitroglycerin (200 microg) was administered in five Yorkshire pigs. Coronary cross-sectional luminal area was measured with intravascular ultrasound at various time intervals. The effects of intracoronary nitroglycerin on coronary luminal area were used for comparison.
  
  
  RESULTS
  Transatrial pericardial access required 1 to 3 min in all animals. Intrapericardial nitroglycerin was associated with a mean 31.7% increase in luminal area at 5 min (p < 0.001). Vasodilation peaked between 5 and 10 min and persisted for 15 min. In contrast, intracoronary nitroglycerin was associated with a smaller mean increase in luminal area (20.3% at 5 min, p < 0.01) that disappeared by 10 min. Significant systemic hypotension was observed at 3 min with intracoronary but not with intrapericardial nitroglycerin.
  
  
  CONCLUSIONS
  Sustained coronary vasodilation can be achieved with intrapericardial delivery of nitroglycerin without systemic hypotension. Nitric oxide donors with longer half-lives could prove beneficial in the treatment of myocardial ischemic syndromes when administered through this route. Transatrial pericardial access offers a novel route for local cardiac drug delivery.
authors.affiliation: Cardiology Division and Institute for Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA. swaxman@caregroup.harvard.edu
authors.forename: S
authors.initials: S
authors.lastname: Waxman
authors.forename: R
authors.initials: R
authors.lastname: Moreno
authors.forename: K A
authors.initials: KA
authors.lastname: Rowe
authors.forename: R L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage*; D010496:Pericardium; D013552:Swine; D018084:Ultrasonography, Interventional; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents; D005996:Nitroglycerin