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EXPERIMENTAL STUDIES

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

Sergio Waxman, MD^* , Ricardo Moreno, BA, Katharine A. Rowe, AB^* and Richard L. Verrier, PhD, FACC^*

^* Cardiology Division and Institute for Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA

Manuscript received August 28, 1998; revised manuscript received January 27, 1999, accepted February 25, 1999.

Reprint requests and correspondence: Dr. Sergio Waxman, Beth Israel Deaconess Medical Center, West Campus, Cardiology Division, One Deaconess Road, Boston, Massachusetts 02215
swaxman{at}caregroup.harvard.edu

OBJECTIVES

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 µg) 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.

Abbreviations and Acronyms   bFGF = basic fibroblast growth factor   NO = nitric oxide

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