Myocardial perfusion and performance after indomethacin administration in newborn lambs

Indomethacin is a drug widely used to achieve pharmacologic closure of a patent ductus arteriosus in the premature infant. In several vascular beds (brain, kidney, intestine), indomethacin has been shown to cause vasoconstriction. Possible negative effects on myocardial blood flow and performance could be deleterious in premature infants with limited cardiac reserve. Before, during, and 30 and 60 min after administration of 1 mg.kg-1 of indomethacin in nine newborn lambs, we measured coronary blood flow velocity (Doppler flow probe around the left circumflex coronary artery), left ventricular (LV) pressure (by tip manometer) and volume (by conductance catheter technique), cardiac output, arterial pressure, arterial and venous saturations and calculated systemic and coronary vascular resistance, LV systolic function by the end-systolic pressure-volume relationship, and myocardial oxygen extraction. To investigate the effect of indomethacin on the flow regulation of the coronary vascular bed, we measured coronary flow and LV function under different levels of myocardial demand, achieved by stepwise occluding of the descending aorta. During indomethacin infusion, coronary and systemic vascular resistance increased significantly (by 43 and 76%, respectively), resulting in an increase in arterial pressure from 10.2 to 16.9 kPa, whereas neither coronary flow nor LV systolic function changed despite the increase in afterload. Thirty and 60 min after indomethacin, coronary and systemic vascular resistance had returned to baseline levels and LV systolic function remained unchanged. The relationship between coronary flow and cardiac demand was not different before or after indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)