Impairment of myocardial function induced by particulate contamination of cardioplegic solutions.
The U.S. Pharmacopoeia defines acceptable limits of particle contamination for intravenous solutions. Used conventionally, these solutions are filtered by the lungs, and there are few reports of particle-induced tissue injury to the systemic circulation. We have used an isolated rat heart model to assess whether unfiltered direct intraarterial administration of cardioplegic solutions, as in open-heart surgery, can be damaging to the myocardium. An intravenous solution of U.S. commercial manufacture was selected for evaluation. Particle-counting revealed this solution to be well within the U.S.P. limits. Direct intracoronary infusion of this solution at 20 degrees C and at constant pressure led to an approximate 75% reduction in coronary flow over 20 min. Filtration through a membrane of 0.8-micron porosity largely prevented this reduction of coronary flow. In studies with multidose cardioplegia (3-min infusions every 30 min), hearts given filtered solution recovered almost 90% of their preischemic functional capacity after 3 hr of hypothermic (20 degrees C) ischemic arrest. Hearts given an identical unfiltered solution essentially failed to recover despite the particle counts having conformed to the U.S.P. limit. This functional result was supported by measurement of creatine kinase leakage, which was significantly higher in the unfiltered group. These studies provide an argument for revision of U.S.P. particle limits when applied to intraarterially administered solutions; in particular, we believe that equipment for cardioplegic infusion into coronary arteries should incorporate a 0.8-micron in-line filter.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003402:Creatine Kinase / Q000097:blood; D004340:Drug Contamination; D005374:Filtration; D006324:Heart Arrest, Induced; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D003402:Creatine Kinase