Effect of aminophylline on the pulmonary and systemic hemodynamic response to group B beta-hemolytic Streptococcus and leukotriene D4 in newborn lambs.

Aminophylline, a methyl xanthine, has been used for many years in the treatment of apnea of prematurity and bronchospasm. Aminophylline relaxes smooth muscle through several proposed mechanisms. We hypothesized that aminophylline might be effective in relaxing preconstricted pulmonary vascular smooth muscle and would be ideally suited for clinical trial in babies with pulmonary hypertension. To test this hypothesis, the haemodynamic response of chronically instrumented newborn lambs to injections of heat-killed Group B beta-hemolytic Streptococcus (GBS) and leukotriene (LT) D4, potent pulmonary vasoconstrictors was compared before and after pretreatment with a clinically therapeutic dose of intravenous aminophylline. GBS (10(9)cfu) significantly increased pulmonary arterial pressure 130%. LTD4 (1.0 microgram/kg) significantly increased pulmonary arterial pressure 142% and systemic arterial pressure 23% and decreased cardiac output 47%. Aminophylline did not significantly affect the baseline variables or alter the pulmonary or systemic haemodynamic response to either stimuli. Therefore, it is unlikely that aminophylline will be clinically useful in the treatment of babies with persistent pulmonary hypertension whose etiology is infectious or leukotriene-mediated.