Effect of fetal anaemia on myocardial ischaemia-reperfusion injury and coronary vasoreactivity in adult sheep.
OBJECTIVE
We investigated whether chronic fetal anaemia affects myocardial infarct in adulthood and elicits functional modifications in adult coronary vasoreactivity.


METHODS
Seven-month-old sheep that were made anaemic in utero and transfused to normal haematocrit before birth were studied. Infarct size was determined by tetrazolium after 1-h ischaemia (occlusion of the mid of left anterior descending artery) and 2-h reperfusion. The dose-response to vasoconstrictors and vasodilators was assessed in small resistance coronary arteries.


RESULTS
There were no significant differences between the animals previously subjected to in utero anaemia and the control animals regarding the percentage infarct size and the area-at-risk to the left ventricle. The ventricular function (dP/dt) was preserved. The percentage infarct size of the area-at-risk (70.7 +/- 3.5%) was larger than that in the controls (49.8 +/- 4.5%) (P = 0.006). The vascular responses were not altered. Endothelium-dependent relaxation to bradykinin (96.0 +/- 2.6% vs. 98.8 +/- 1.0%) was not affected by PGI(2) inhibitor (94.6 +/- 2.6% vs. 98.5 +/- 1.0%) but significantly reduced by the inhibition of nitric oxide (NO) in both anaemic (P < 0.05) and control (P < 0.001) groups with a significant right shift of EC(50) (P < 0.01). The non-NO-non-PGI(2)-mediated relaxation was slightly potentiated in anaemic animals.


CONCLUSIONS
Exposing fetal sheep to in utero anaemia in late gestation for 3 weeks may increase the susceptibility of adult hearts to ischaemia-reperfusion injury without major alterations in coronary vasomotor responsiveness. The impact of in utero anaemia at earlier period of pregnancy and on the earlier or later life of the adult is yet to be further investigated.
Yang
Q
Q
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA. qyang@surgery.cuhk.edu.hk
Hohimer
A R
AR
Giraud
G D
GD
Van Winkle
D M
DM
Underwood
M J
MJ
He
G-W
GW
Davis
L E
LE
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000740:Anemia / Q000196:embryology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D002908:Chronic Disease; D007213:Indomethacin / Q000494:pharmacology; D009203:Myocardial Infarction / Q000453:epidemiology*; D015428:Myocardial Reperfusion Injury / Q000196:embryology*; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002317:Cardiovascular Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007213:Indomethacin