Quantitative electron microscopic study of the hypoxic fetal sheep heart.
In order to determine the effects of chronic, high-altitude hypoxia on the ovine fetal heart, we exposed pregnant ewes to 3,820 m beginning at 30 days gestation. We previously showed that following approximately 110 days of hypoxia the fetal heart showed significant reduction in cardiac output (76% of control) and contractility, and elevated levels of citrate synthase and lactate dehydrogenase. To investigate ultrastructural influences on these observed physiologic changes at altitude, we hypothesized that the volume densities of myofibrils and mitochondria, and glycogen content would be reduced in the ovine fetal heart and that this may contribute to contraction and cardiac output deficits in hypoxia. Mitochondria and myofibril volume density were determined by standard point-counting techniques and glycogen content was determined by biochemical analysis. The glycogen content from the hypoxic right ventricle (4.8 +/- 0.3%) was significantly lower than in control right ventricle (6.8 +/- 0.5%) and both left ventricles (hypoxia, 7.2 +/- 0.5; control, 7.8 +/- 0. 4%). Total mitochondrial volume density was also significantly reduced following hypoxia (15.5 +/- 0.7%) compared to controls (16.9 +/- 0.4%). As is common in the ovine fetal heart, the myofibril volume density of the right ventricle from both groups was significantly higher than the left ventricle (RV, 58.6 +/- 1.6; LV 54.3 +/- 0.9%). However, it was not different between control and high altitude. In support of our hypothesis, we may speculate that deficits in the quantity of myocyte glycogen and mitochondria contribute to the observed reduction in cardiac output and contractility, despite the upregulation of citrate synthase and lactate dehydrogenase. In contrast, myofibril volume density was unchanged.
Lewis
A M
AM
Center for Perinatal Biology, Loma Linda Medical School, Loma Linda, California 92350, USA. dmlewis@budgetblinds.com
Mathieu-Costello
O
O
McMillan
P J
PJ
Gilbert
R D
RD
D000531:Altitude; D000818:Animals; D005260:Female; D005318:Fetal Heart / Q000648:ultrastructure*; D006003:Glycogen / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism / Q000648:ultrastructure; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D009210:Myofibrils / Q000648:ultrastructure; D011247:Pregnancy; D012756:Sheep
D006003:Glycogen