Figure 1.

Hemodynamic signatures and diuretic impacts of apelin-13 (APLN-13) and Elabela (ELA) are distinctive and differential in healthy sheep. (A) Study Design: Sheep were maintained under general anesthesia and mechanical ventilation. Following instrumentation and clinical stabilization, displayed data were recorded at baseline (bsl) and following infusion of 20 min-incremental doses of APLN-13 or ELA (d1: 0.025; d2: 0.25; d3: 2.5; d4: 6.25; and d5: 12.5 nmol/kg/h) vs. normal saline (NS). Basal fluid delivery: Ringer Lactate (RL, 3 mL/kg/h) and 5% D-glucose (2 mL/kg/h). See “Methods” section for details. (B–I) Heart rate, global end-diastolic volume, mean arterial pressure; end-systolic pressure; systemic vascular resistance; cardiac output, dP/dt max and dP/dt min were assessed by PiCCO-Volef thermodilution or left ventricular catheterization. Above or from 2.5 nmol/kg/h, APLN-13 enhanced cardiac output and dP/dt max whereas ELA decreased mean arterial pressure and end-systolic pressure. (J) Urinary output was measured by percutaneous bladder catheterization. APLN-13 increased urine output at 2.5 nmol/kg/h. All results are expressed as the mean ± SEM (n = 6/group). Statistical analyses for quantitative variables were performed with a paired Student’s t-test (normally distributed variables) or a Mann Whitney U test (nonnormally distributed variables). Dose–response and time-course analyses were performed with repeated measures two-way ANOVA followed by Tukey’s multiple comparison test. *p < 0.05, **p < 0.01 vs. normal saline (NS)-infused sheep.