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 < 0.05) and lower compliance (1.53 ± 0.21 vs 1.88 ± 0.33 ml · mm Hg, p < 0.05). Healthy calves and pigs had significantly lower resistance (calf: 0.63 ± 0.07 mm Hg · s/ml; pig: 0.90 ± 0.07 mm Hg · s/ml) and higher compliance (calf: 2.79 ± 0.37 ml · mm Hg; pig: 2.80 ± 0.64 ml · mm Hg) when compared to humans (p < 0.05) with normal or failing hearts. 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.