The potential hazard of particulate contamination of cardioplegic solutions

The potential hazard of particulate debris in unfiltered cardioplegic solutions was assessed using the isolated rat heart preparation. Five intravenous solutions were evaluated: These were manufactured by three pharmaceutical firms (two United States and one British) and are commonly used as bases for preparing clinical cardioplegic solutions. Particles were counted in each solution, and each fell well within the limits for particle contamination defined by both the United States and the British Pharmacopoeias. Intracoronary continuous infusion of each solution over 20 minutes at constant temperature and pressure (20 degrees C, 60 cm H2O) resulted in a progressive reduction in coronary flow (mean reduction 55.7% +/- 6.6%) due to a rise in coronary vascular resistance; filtration of these same solutions through a 0.8 micron filter just prior to their entry into the heart largely prevented these coronary vascular changes. The filter was examined by scanning electron microscopy and showed amorphous and crystalline debris. Nifedipine (0.1 mumol/L) added to the cardioplegic solution reduced by almost 50% the impairment in coronary flow seen in the unfiltered group. In more clinically relevant studies of 180 minutes of hypothermic (20 degrees C) ischemia using multidose cardioplegia (3 minutes every 30 minutes), hearts infused with filtered solution recovered almost 90% of their preischemic functional capacity. Hearts receiving identical but unfiltered solution, however, essentially failed to recover (p less than 0.001) and had significantly higher levels of creatine kinase leakage. These results suggest that commercially produced solutions conforming to limits of particulate contamination acceptable for intravenous administration may prove harmful if given unfiltered directly into coronary arteries, with the likely mechanism of action being particle-induced coronary vasoconstriction.