Absence of robust ischemic preconditioning by five 1-minute total umbilical cord occlusions in fetal sheep

Abstract

To determine to what extent a series of five 1-minute total umbilical cord occlusions, intended to induce ischemic preconditioning (IP), affects the physiologic responses to a 10-minute total umbilical cord occlusion (damaging insult [DI]) 1 hour later and provides cardio- and neuroprotection. In 14 chronically catheterized late gestation fetal sheep (127-131 days' gestation), we performed a 10-minute total umbilical cord occlusion (DI), preceded by a series of five 1-minute total cord occlusions with 2-minute intervals (5CO, n = 7) or sham occlusions (n = 7) 1 hour prior to DI. The 5CO induced a reduction in the arterial partial pressure of oxygen (Po 2) from 21 ±1 to 14 ±3 Torr, arterial O 2 content from 6.9 ± 0.4 to 3.1 ± 0.7 vol%, and increases in the partial pressure of carbon dioxide (Pco 2) from 46 ± 2 to 58 ± 3 Torr, and [H +] from 43 ± 1 to 54 ± 2 nM. 5CO reduced fetal heart rate from 178 ± 6 to 151 ± 6 beats per minute (bpm), and increased arterial pressure from 45 ± 1 to 57 ± 2 mmHg, cerebral blood flow (CBF) from 100 ± 3 to 129 ± 10%, and cerebral heat production (H brain) from 25 ± 2 to 29 ± 1%°C. The responses to DI were not significantly different between the groups without and with 5CO; values for Po 2 were 5.6 ± 1.5 and 5.8 ± 1.9 Torr, O 2 content 0.6 ± 0.1 and 0.8 ± 0.1 vol%, lactate 10.7 ± 0.7 and 10.8 ± 0.7 mM, fetal heart rate 97 ± 5 and 87 ± 8 bpm, mean arterial pressure 22 ± 3 and 21 ± 2 mmHg, CBF 50 ± 10 and 36 ± 5%, and H brain 7.0 ± 1.4 and 5.9 ± 1.1%°C, respectively, except for Pco 2 (126 ± 4 and 112 ± 2 Torr) and [H +] (126 ± 3 and 114 ± 3 nM). Histologic proof of cardio- or neuroprotection by 5CO could not be obtained because five fetuses died before they were to be killed at day 3 after the experiment; two fetuses in the 5CO group demonstrated major histologic damage of myocardium and brain. In the late gestation fetal sheep, a series of five 1-minute total umbilical cord occlusions did not result in major changes in physiologic responses to a hypoxic-ischemic DI 1 hour later. In addition, the procedure did not result in robust cardio- and neuroprotection, in contrast to IP reported in adults. Copyright © 2004 by the Society for Gynecologic Investigation.