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


METHODS
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.


RESULTS
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% degrees 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% degrees 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.


CONCLUSIONS
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.
Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California, USA. f.lotgering@obgyn.umcn.nl
Fred K
FK
Lotgering
John M
JM
Bishai
Piet C
PC
Struijk
Arlin B
AB
Blood
Christian J
CJ
Hunter
Kerby C
KC
Oberg
Gordon G
GG
Power
Lawrence D
LD
Longo
D000818:Animals; D001158:Arteries; D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply; D002245:Carbon Dioxide / Q000097:blood; D003250:Constriction; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005865:Gestational Age; D006340:Heart Rate, Fetal; D019194:Ischemic Preconditioning / Q000379:methods*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011247:Pregnancy; D012756:Sheep; D013997:Time Factors; D014470:Umbilical Cord
D002245:Carbon Dioxide; D010100:Oxygen