Persistent primary coronary dilation induced by transatrial delivery of nitroglycerin into the pericardial space: A novel approach for local cardiac drug delivery

OBJECTIVES We compared the effects of intrapericardial and intracoronary ni troglycerin on coronary cross-sectional area as assessed by intravascular u ltrasound and demonstrated the feasibility of local cardiac drug delivery b y a newly developed method to access the normal pericardial space through t he right atrial appendage. BACKGROUND Studies of nitric oxide (NO) donors have suggested that their an tiarrhythmic and antiproliferative properties are more effective when admin istered by the intrapericardial rather than intravascular route. We postula ted that NO donors delivered intrapericardially would also cause sustained coronary vasodilation without significant systemic hypotension. METHODS Intrapericardial nitroglycerin (200 mu g) was administered in live Yorkshire pigs. Coronary cross-sectional luminal area was measured with int ravascular ultrasound at various time intervals. The effects of intracorona ry nitroglycerin on coronary luminal area were used for comparison. RESUTLS 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 mi n and persisted for 15 min. In contrast, intracoronary nitroglycerin was as sociated 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 obse rved at 3 min with intracoronary but not with intrapericardial nitroglyceri n. CONCLUSIONS Sustained coronary vasodilation can be achieved with intraperic ardial delivery of nitroglycerin without systemic hypotension. Nitric oxide donors with longer half-lives could prove beneficial in the treatment of m yocardial ischemic syndromes when administered through this route. Transatr ial pericardial access offers a novel route for local cardiac drug delivery . (C) 1999 by the American College of Cardiology.