17β-Estradiol effect on critical cardiac output with reduction of cardiac output in oophorectomized sheep

Abstract

Acute administration of 17β-estradiol (E2β) leads to increases in cardiac output, oxygen delivery, and oxygen consumption and increases the critical cardiac output in the nonpregnant sheep. We sought to determine whether the lack of a critical cardiac output or flow-dependent oxygen consumption during states of low cardiac output in late gestation can be reproduced in nonpregnant sheep treated with estrogen. We studied five nonpregnant oophorectomized sheep in a randomized crossover design by placing catheters in the pulmonary artery, the right atrium, and the descending aorta. Three experiments were randomly performed on each sheep 3 to 5 days apart: 1) without estrogen or vehicle, 2) 2–3 h after intravenous administration of vehicle, and 3) 2–3 h after intravenous E2β (3 μg/kg). Cardiac output was gradually reduced while hemodynamic, cardiorespiratory, acid-base, and metabolic variables were simultaneously evaluated. There was a 70% increase in cardiac output in animals given E2β compared with that in the same animals given either vehicle or nothing (194.0 ± 13.0, 120.0 ± 14.5, and 114.0 ± 16.2 ml ⋅ min−1 ⋅ kg−1, respectively; P < 0.05). Oxygen consumption was twofold higher in the E2β series compared with that in the no-treatment and vehicle series (10.01 ± 1.3, 6.04 ± 0.77, and 4.52 ± 0.42 ml O2 ⋅ min−1 ⋅ kg−1, respectively; P < 0.05). Tissue oxygen extraction was unaltered by estrogen. However, tissue oxygen extraction at the critical cardiac output was lower in the estradiol group. In relation to oxygen consumption, all three groups demonstrated a critical cardiac output when cardiac output was gradually reduced. However, the level of critical cardiac output was significantly higher in the E2β group (68.4 ± 2.4, 42.8 ± 2.6, and 46.2 ± 2.6 ml ⋅ min−1 ⋅ kg−1, respectively; P < 0.05). We conclude that E2β exhibits increases in systemic tissue blood flow and oxygen consumption. Animals given E2β show increases in critical cardiac output and impairment of tissue oxygen extraction at critical cardiac output, which leads to development of flow-dependent oxygen consumption at higher cardiac outputs than in the control animals.