Abstract 183 Poster Session II, Sundays, 5/2 (poster 249)

Introduction: Dexamethasone is used to treat bronchopulmonary dysplasia in premature infants. Previous studies indicate this drug may produce ventricular dysfunction and cardiomyopathy during a 6 week course of therapy ( Bensky et al., Pediatrics 97;1996). We studied the incidence, characteristics, and potential mechanisms for cardiac dysfunction in infants receiving dexamethasone (JCMC IRB#95-13). We also studied the effects of dexamethasone on contractions in human cardiac myocyte clusters (ETSU IRB#97-076e). Methods: Patients were hospitalized in the NICU at Johnson City Medical Center between April 1995 and February 1998 (n=37). Gestational age was 26±2.5 weeks (mean±SD), and birthweight was 842±318 grams. We initially administered dexamethasone at 0.5mg/kg/day, and tapered over 23.6±11.7 days. Changes in ventricular function, dimensions, and wall thickness were measured with echocardiography. Systemic blood pressures were measured by cuff, or using arterial lines when available. Glucose intolerance was based on elevated serum glucose levels. For studies on myocyte clusters, ventricular myocardium from 7-11 weeks gestation human fetuses were minced, digested, and plated in enriched medium. Spontaneously contracting clusters were selected for study, and cell shortening was measured with a video edge detector at a paced rate of 0.25 Hz. Results: Cardiomyopathy developed in 24 of 37 patients receiving dexamethasone (64.9%), and was observed in patients receiving ≥14 days of therapy. The incidence of systemic hypertension and glucose intolerance was similar in patients with and without cardiomyopathy. When the myocyte clusters (n=5, from 3 hearts), were exposed acutely to dexamethasone, contractions were unchanged after 1 and 10 mM concentrations, decreased after 20 and 45 mM concentrations, and returned to baseline after perfusing the clusters with dexamethasone-free Tyrodes solution. When cultured chronically in 10 mM dexamethasone, contraction amplitude in the myocyte clusters decreased 50% after 1 week in culture, and 64% after 2 weeks in culture (P<0.025). Time to peak contraction and relaxation half-time were unchanged. Myocyte clusters from the same hearts cultured the same length of time without dexamethasone, had no change in contraction amplitude, time to peak contraction or relaxation half-time. Conclusion: There is a high incidence of cardiomyopathy in premature infants treated for bronchopulmonary dysplasia with ≥14 days of dexamethasone. The incidence of cardiomyopathy is not related to hypertension of hyperglycemia. Contractions in myocyte clusters from fetal hearts are decreased after acute and chronic exposure to dexamethasone. The mechanism for decreased contractions and cardiomyopathy is undetermined.