Transatrial access to the normal pericardial space for local cardiac therapy: preclinical safety testing with aspirin and pulmonary artery hypertension.

The reliability, rapidity, and safety of nonsurgical, transatrial pericardial access for local cardiac therapy have been demonstrated in healthy animals. Since many patients take aspirin or have increased right-sided pressures, we evaluated the procedure's safety under these conditions. Transatrial pericardial access was performed in anesthetized pigs following aspirin administration (162 mg p.o., n = 6) or during experimental pulmonary artery hypertension (n = 4 different animals) and required only 3 minutes following guide catheter positioning. Platelet aggregability testing with arachidonic acid confirmed aspirin effectiveness. Mean pericardial fluid hematocrit was 0.1 +/- 0.1% after 2 days of aspirin therapy and 1.9 +/- 1.1% at sacrifice 24 hours later (NS). Mean pericardial fluid hematocrit was 1.0 +/- 0.5% after 45 minutes of pulmonary artery hypertension and 4.3 +/- 0.8% at sacrifice 30 minutes later (NS). Histologic analysis in both groups revealed a small thrombus and localized inflammation at the site of puncture. Neither aspirin use nor pulmonary artery hypertension causes significant bleeding into the pericardial space following transatrial access and thus does not preclude this route for local cardiac drug delivery.

Preclinical safety testing of percutaneous transatrial access to the normal pericardial space for local cardiac drug delivery and diagnostic sampling.

The safety of a percutaneous method and streamlined catheter system to access the normal pericardial space via the right atrial appendage for drug delivery and diagnostic sampling was demonstrated in 20 anesthetized pigs. Access was successfully accomplished in all animals within 3 min of guide catheter positioning and was documented by fluoroscopic imaging and pericardial fluid sampling. The animals were sacrificed at 24 hr (n = 10) and 2 weeks (n = 10) for histopathologic analysis. Mean pericardial hematocrit was 1.1% +/- 0.3% at initial sampling, 4.3% +/- 1.4% at 24 hr (P = 0.005 vs. baseline), and 0.4% +/- 0.2% at 2 weeks (P = 0.13 vs. baseline). At 24 hr, there was local inflammatory reaction in the atrial wall and a small thrombus at the site of puncture. At 2 weeks, no significant inflammatory changes or pericarditis were evident. The technique is well tolerated with no apparent adverse complications. Advances in intrapericardial therapeutics and diagnostics will direct the clinical application of this novel approach in human subjects.