Alteration of the pulsatile load in the high-altitude calf model of pulmonary hypertension

Abstract

We compared main pulmonary arterial elasticity and global pulmonary arterial compliance in control and high-altitude (HA) calves to determine whether 1) changes in pulmonary arterial elasticity are contributing to an increase in the oscillatory load of the right ventricle in this model of pulmonary hypertension and 2) measured changes in stiffness of the HA calves' arterial wall are the result of both an increase in pressure and an alteration of the material properties of the HA calves' arterial wall. Newborn calves were placed at 4,300 m simulated altitude for 14 days, and control calves were kept at 1,500 m. The HA calves were then reacclimatized to 1,500 m for 24 h so that baseline pressures of the two groups were similar. Open-chest main pulmonary arterial and right ventricular micromanometric pressures, ultrasonic main pulmonary arterial diameter, and green dye flow were measured under baseline conditions and then under moderate and severely hypoxic conditions to make measurements at both baseline and increased pulmonary pressures. At elevated pressures, the pressure-diameter relationship was noted to be nonlinear, and a characteristic late systolic peaking of the right ventricular pressure waveform was seen. The Peterson pressure-strain modulus, pulse wave velocity, characteristic impedance, and global compliance (3 element windkessel) were calculated. The calculated variables were all shown to be pressure dependent, and no intrinsic differences in stiffness were seen between the control and HA animals when mean pressure was taken into account. Pulmonary arterial histology demonstrated, however, a characteristic increase in wall thickness in the HA animals. Thus, in this model of pulmonary hypertension, major changes in elasticity and pulsatile load are primarily due to an increase in pulmonary pressure. The structural changes present in the HA calves' arterial wall did not separately produce any measurable changes in arterial distensibility or the oscillatory load.