587 - Recombinant human insulin-like growth factor 1 and binding protein 3 does not alter heart weight or function in mechanically ventilated preterm lambs
Assistant Professor University of Utah Salt lake City, Utah, United States
Background: Exogenous insulin-like growth factor 1 (IGF-1) augments heart growth and function in some animal models. IGF-1 increases heart weight in late gestation fetal sheep but not in term newborn sheep postnatally. However, the impact of physiological replacement of IGF-1 on the postnatal preterm heart is not known. Objective: To determine if physiological replacement of recombinant human (rh) IGF-1 bound to rh binding protein 3 (rhIGF-1 complex) alters heart weight or function. Design/Methods: Preterm lambs at 128d gestation were exposed to antenatal steroids and treated with perinatal surfactant and postnatal caffeine, and resuscitated and supported by invasive mechanical ventilation for 7d. The control group received vehicle (IGF-1 diluent in saline; continuous IV infusion; n=8; 5F 3M). The treated group received rhIGF-1 complex (optimized dose of 1.5 mg/kg/d IV; n=9; 4F 5M). Echocardiography was used to measure cardiac morphometry, ventricular pressure relationships, and function in a subset of lambs (Vehicle: n=4; 3F 1M; rhIGF-1 complex: n=5; 1F 4M). Hearts were weighed, dissected, and right and left heart components weighed individually. Results: No statistically significant differences were detected for birth weight, body weight after 7d, or weights of whole heart, right ventricle (RV), combined left ventricle (LV) + intraventricular septum (IVS), or ratio of RV to LV+IVS (index of RV hypertrophy) between groups (Fig 1) or by sex. Also, no statistically significant differences were detected in hemodynamics at time of echocardiogram or echocardiographic measurements of morphometry, ventricular pressure relationships, or function between groups (Table 1). Sex differences in echocardiographic measures were not assessed because sex distribution was unequal.
Conclusion(s): We conclude that postnatal continuous infusion of rhIGF-1 complex did not alter heart growth or function in preterm lambs that were mechanically ventilated for 7d. Current analyses are quantifying capillary growth in the myocardium. This work was supported by a research grant to the University of Utah (K. H. Albertine) from OHB Neonatology Ltd and Division of Neonatology at University of Utah.
