Human, Bovine and Porcine Systematic Vascular Input Impedances Are Not Equivalent: Implications for Device Testing and Xenotransplantation in Heart Failure

Background Advanced therapies for heart failure (HF), such as mechanical circulatory support (MCS) devices and xenotransplantation, are usually tested in bovine and porcine models. This approach assumes a priori that animal (patho)physiology will closely match that of humans. Systemic aortic input impedance (Z ART ) is an important physiologic determinant of left ventricular (LV) performance. We tested the hypothesis that Z ART is lower in bovine and porcine than in humans with normal or failing hearts. Methods High-fidelity aortic pressure and flow waveforms were recorded intra-operatively at native and paced heart rates of 100 beats per minute (bpm) in adult human patients with normal LV function ( n = 13) or end-stage HF ( n = 15), and normal calves ( n = 10) and pigs ( n = 18). Fast Fourier transformation was used to calculate Z ART , and arterial resistance and compliance were estimated using a 4-element Windkessel model. Results Humans with HF had greater Z ART than those with normal LV function, characterized by higher resistance (1.16 ± 0.12 vs 1.00 ± 0.10 mm Hg · s/ml, p p p Conclusions Z ART is significantly lower in calves and pigs than in humans with or without HF. This finding has important implications for the pre-clinical testing of MCS devices and xenotransplants, which are usually examined in bovine and porcine models, respectively. Specifically, these therapies may respond differently in humans than animals due to non-equivalence of systemic after-load.