preterm and full-term newborn lambs

We studied left ventricular performance and contractility after volume loading in lambs at 122 days (group I, n = 9) and 139 days gestational age (group IL, n = 9) and in 8-day-old full-term lambs (group III, n = 7). All were mechanically ventilated; each preterm lamb was treated with surfactant to stabilize pulmonary function and the ductus arteriosus was occluded with an inflated catheter balloon. Cineangiograms, left ventricular and vascular pressures, and the isovolumetric index of contractility, first derivative of left ventricular pressure (dP/dt), were recorded before and after three successive whole blood volume infusions of 10 ml/kg (total 30 ml/kg). The left ventricular enddiastolic volume per kilogram and stroke volume per kilogram increased significantly in all groups after volume infusion; these measurements and heart rate and systemic vascular resistance did not differ significantly between the groups either before or after the infusions. The left ventricular peak dP/dt did not change significantly within the groups during the volume infusions. The left ventricular stroke work was greatest in full-term animals and increased significantly in all groups after volume infusion. Thus, the left ventricles of the preterm and full-term lambs had quantitatively similar Frank-Starling responses and there was no increase in contractility during the infusions of whole blood. However, the left ventricle of the full-term lamb is capable of generating greater stroke work than that of the preterm lamb. These findings may contribute to the understanding of developmental aspects of postnatal circulatory adaptation. Circulation 73, No. 5, 1042-1049, 1986. IT HAS BEEN suggested that the left ventricle of the premature infant may be less capable than the mature left ventricle of adjusting to transitional circulatory changes required postnatally, such as increasing volume and resistance work.' 2 These conclusions followed from ultrastructural observations and from developmental studies of myocardial contraction in isolated muscle preparations, and from comparative studies of left ventricular performance in the intact fetus and full-term newborn lamb.'-' Until recently developmental studies of postnatal left ventricular performance were not possible in newly born preterm animals, because prematurity was associated with a From the University of California, Los Angeles, School of Medicine, and Harbor-UCLA Medical Center, Department of Pediatrics, Torrance, CA. Supported by grants 590 GLO3 and 676 IG from the American Heart Association, Greater Los Angeles Affiliate, NIH grant HD 12714, and a grant from the Upjohn Corporation, Kalamazoo, MI. Address for correspondence: Barry G. Baylen, M.D., Division of Pediatric Cardiology, Harbor-UCLA Medical Center, 1000 West Carson St., Torrance, CA 90509. Received July 9, 1985; revision accepted Feb. 13, 1986. 1042 rapid deterioration of pulmonary function and metabolic status.9 10 Now, however, acceptable pulmonary function can be maintained with the combined use of surfactant treatment and mechanical ventilation. 10 The purpose of this study was to characterize developmental aspects of left ventricle pump performance and contractility in surfactant-treated preterm lambs and in full-term lambs under conditions simulating those encountered in the neonatal intensive care setting. Material and methods We studied the hemodynamic responses to volume infusions in three groups ofpreterm and full-term lambs. Group I lambs (n 9) were 122 ± 2 (SD) days gestational age, group II lambs (n = 9) were 139 + 2 days gestational age, and group III (n = 7) consisted of 8 + 3 day old spontaneously delivered full-term lambs. The preterm lambs were delivered by cesarean section of date-bred Western mixed-breed ewes. The ewes (groups I and II) were premedicated with intramuscular injections of ketamine (800 mg) and atropine sulfate (3 mg), and surgery was performed under spinal anesthesia. The head and neck of each lamb were exposed through an anterior midline abdominal incision, and an appropriately sized endotracheal tube was secured in the CIRCULATION by gest on N ovem er 7, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-VENTRICULAR PERFORMANCE trachea by tracheotomy under local anesthesia. Preterm lambs at 122 days gestational age cannot be successfully ventilated without surfactant treatment, whereas preterm lambs at 139 days gestational age do not require surfactant treatment for adequate ventilation. Therefore, before delivery and initiation of breathing, the group 1 lambs (122 days gest age) were treated by tracheal instillation with 15 ml of 0.45M NaCl containing natural sheep surfactant in suspension (50 mg lipid per kg). The surfactant was isolated from lung lavage from adult ewes.10 Each preterm lamb was then delivered and cord blood was drawn for measurements of pH and arterial blood gases. The cord was clamped and cut, and each lamb was then ventilated with a pressure-limited infant ventilator (Sechrist Industries) at initial settings of 30 breaths/min, a positive end-expiratory pressure of 2 cm H20, a peak inspiratory pressure of 28 cm H20, and an inspiratory time of 1 sec. A No. 5F catheter was passed via an umbilical artery to the distal thoracic aorta, and each lamb was paralyzed with intravenous pancuronium bromide (0.1 mg/kg). Rectal temperature was maintained at 38° to 390 C with a heating pad and heat lamps. Blood losses were replaced with equivalent volumes of freshly collected anticoagulated and filtered maternal blood. Peak inspiratory pressures, rates, and inspired oxygen concentrations were changed to maintain arterial blood gas values in the range Po2 50 to 80 mm Hg, Pco2 30 to 45 mm Hg, and pH 7.35 to 7.45. Arterial blood gases and pH were measured at 20 to 30 min intervals with a Radiometer blood gas analyzer. Group III lambs were brought to the laboratory where they were premedicated with intravenous atropine, 0.01 mg/kg, and ketamine, 0.5 mg/kg. Each lamb was intubated with a 5.5 mm endotracheal tube by direct laryngoscopy. The lambs were paralyzed with pancuronium bromide (0.1 mg/kg) and ventilatory settings were adjusted to maintain blood gases and pH within similar and acceptable ranges for study of cardiovascular performance. Catheter placement. The lambs were catheterized under local anesthesia through small external cutdowns while fluoroscopy and pressure monitoring1 were performed (figure 1 ). The tracheotomy incision was extended laterally; two fluid-filled catheters were passed via the right external jugular vein into the right atrium (No. SF argyl catheter) and into the main pulmonary artery (No. 5 flow-directed balloon angiography catheter). A No. SF transducer-tipped catheter (Millar Instruments, Inc.) was advanced retrogradely from the right carotid artery to the left ventricle. A No. 4F flow-directed balloon angiographic catheter was passed via the umbilical vein (femoral vein in group IIl) through the foramen ovale and advanced to the left ventricle. A No. 5F polyvinyl catheter was advanced from the umbilical artery (femoral artery in group I1I) to the descending thoracic aorta. In group I and Il lambs the catheter in the pulmonary artery was advanced into the ductal lumen and the balloon was then inflated to occlude the ductus arteriosus. The catheter was secured and occlusion during the duration of the protocol was confirmed by pressure monitoring and fluoroscopy. The ductus arteriosus was occluded in preterm lambs to eliminate the variable influence of left-to-right ductal shunting on ventricular performance. Using this method, we have occluded the ductus arteriosus for several hours in preterm lambs. 12 Measurements and calculations. The cardiovascular pressures were continuously monitored and recorded with a multichannel photographic recorder (Hewlett-Packard). Transducers were calibrated with a mercury manometer and referred to zero position at the midthoracic level (lateral decubitus position) before each series of measurements. The transducer-tipped catheter (left ventricular) was similarly calibrated and was periFIGURE 1. Image obtained at catheterization (left) and single-frame of cine left ventriculogram (right) from the closed-chest preterm and full-term lamb preparation. Venous catheters are advanced to the right atrium (RA) and to the pulmonary artery. A contrast-filled inflated catheter balloon (arrow) occludes the lumen of the ductus arteriosus (upper left). A flexible No. 4F balloon angiography catheter (angio cath; Edwards, Santa Ana, CA) and transducer-tipped catheter (dP/dt) have been introduced into the left ventricle (LV). Vol. 73, No. 5, May 1986 1043 by gest on N ovem er 7, 2017 http://ciajournals.org/ D ow nladed from