Quantitative electron microscopic study of the hypoxic fetal sheep heart

Abstract

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 Ϸ110 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 Ϯ 0.3%) was significantly lower than in control right ventricle (6.8 Ϯ 0.5%) and both left ventricles (hypoxia, 7.2 Ϯ 0.5; control, 7.8 Ϯ 0.4%). Total mitochondrial volume density was also significantly reduced following hypoxia (15.5 Ϯ 0.7%) compared to controls (16.9 Ϯ 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 Ϯ 1.6; LV 54.3 Ϯ 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.

Field Investigation of Perinatal Mortality in Friesian Cattle Associated with Myocardial Degeneration and Necrosis

“…Other evidence to support this hypothesis comes from the PAS-stained sections where glycogen content was lower than expected. In their study of ovine fetal hypoxia, Lewis et al (1999) found that lowered myocyte glycogen content and mitochondrial volume density was associated with reduction in cardiac output and contractility. The fetal heart is resistant to acute hypoxia, because of an increased reliance on anaerobic gycolysis that enhances utilization of endogenous glycogen.…”

Adaptations to diving hypoxia in the heart, kidneys and splanchnic organs of harbor seals (Phoca vitulina)

“…For the first category of studies, research has shown that there is either no change or a decrease in aerobic indicators of the heart and liver (Kayar and Banchero, 1987;Costa et al, 1988;Lewis et al, 1999;Kennedy et al, 2001). For studies of the second type, CS (Hochachka et al, 1982) and LDH activities of the heart were increased (Vergnes, 1971;Penney, 1974;Barrie and Harris, 1976;Ohtsuka and Gilbert, 1995).…”

Assessing the effects of mitofusin 2 deficiency in the adult heart using 3D electron tomography

“…Investigating the role of the mitochondrial fusion and fission proteins on mitochondrial morphology in the adult heart, in which mitochondria are characteristically arranged in rigid networks aligned with the myofibrils, can be quite challenging using current experimental techniques: 2D electron microscopy (EM) is limited to one single 2D plane and can only provide an approximation of mitochondrial shape and size in one planar axis (Lewis et al. ; Picard et al. ; Neary et al.…”