Differential levels of tissue hypoxia in the developing chicken heart

Wikenheiser, Jamie C.; Doughman, Yong Qiu; Fisher, Steven A.; Watanabe, Michiko

doi:10.1002/dvdy.20499

Cited by 54 publications

(63 citation statements)

References 63 publications

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“…9) at ED5 (30% apex-to-base in hypoxic, N 5 10) or ED6 (20%, N 5 5) but apex-to-base activation was present in all 8 hypoxic hearts examined at ED7 (stage 31; P 5 0.008, Chi-square test). Likewise, no differences were spotted in the location of atrial pacemaker (Sedmera et al, 2006), which was shown previously to colocalize with region of increased tissue hypoxia in the vicinity of sinoatrial nodal artery (Wikenheiser et al, 2006). Immunohistochemical examination of the hearts did not reveal any remarkable differences between normoxic and hypoxic hearts; HNK1, marker for neural crest that stains the proximal part of the ventricular conduction system showed normal expression, whereas the PSA-NCAM antibody did not react with quail tissue using protocol with paraffin sections, but stained identically processed chick tissue that served as a positive control (data not shown).…”

Section: Effect Of Hypoxia On Conduction System Maturationmentioning

confidence: 50%

“…The interventricular septum is also site of conduction system formation, correlating with hypoxic regions (Wikenheiser et al, 2006). The functionality of conduction system can be inferred from optical mapping of epicardial activation patterns Sedmera et al, 2006).…”

Section: Effect Of Hypoxia On Conduction System Maturationmentioning

confidence: 99%

“…Effects of hypoxia on cardiac development were studied for some time (Jaffee, 1978;Rouwet et al, 2002;Sharma et al, 2006). Recently, regional differences in myocardial tissue oxygenation during development were described (Wikenheiser et al, 2006), and regions with the lowest oxygen availability in the myocardium of the atria and interventricular septum were correlated with known sites of formation of coronary vessel and pacemaking and conduction system.…”

Section: Introductionmentioning

confidence: 99%

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Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Naňka

Krizova

Fikrle

et al. 2008

The Anatomical Record

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Oxygen availability is one of the necessary prerequisites for normal embryonic development. In our previous study we found that quail embryos incubated under hypoxic conditions (16% O 2 ) die at embryonic day (ED) 9 with signs of heart failure. By ED4 and ED6 we found thinner ventricular wall and increased capillary density. We thus hypothesized that the cause of death would lie in severe myocardial and coronary maldevelopment. ED6 and 7 hypoxic hearts had thinner ventricular wall, especially left. There was a simultaneous increase in capillary density, most pronounced in the interventricular septum. This site corresponds to an area of tissue hypoxia and ensuing increased angiogenesis, and also formation of ventricular conduction system. Hypoxia had a positive effect on normal sequence of maturation of the conduction system evaluated by optical mapping at ED7. In sections from ED9 hypoxic hearts we found, in addition to thinner ventricular walls, irregularities in development of coronary tree (missing coronary ostia, absence of one coronary artery, and irregular arterial wall). This deficiency was due to decreased myocyte proliferation rather than to increased apoptosis. By Indian ink injection through the left ventricle we found in normoxic hearts regular coronary branching pattern, while in the hypoxic ones there was often only an irregular plexus. Embryonic hypoxia thus leads to increased capillarity and trabeculation to minimize diffusion distance. In the subsequent period there is a failure in organization of vascular plexus into normal vasculature, resulting in thin compact myocardium that likely leads to heart failure and embryonic death.

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Section: Effect Of Hypoxia On Conduction System Maturationmentioning

confidence: 50%

Section: Effect Of Hypoxia On Conduction System Maturationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Naňka

Krizova

Fikrle

et al. 2008

The Anatomical Record

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“…It has been proposed that a gradient of hypoxia across the ventricular wall corresponds with the HIF-1-responsive VEGF gene expression both in transcript and protein levels and endothelial tube formation (Tomanek et al, 1999) and that the perturbation of hypoxia can lead to abnormal coronary vascular development (IvnitskiSteele et al, 2004). Our most recent findings for EF5 and HIF-1␣ staining in the chicken embryo heart (Wikenheiser et al, 2006) suggest that other regions in addition to the OFT myocardium are hypoxic and correlate with regions that have been shown to exhibit apoptosis in chicken and mouse embryos such as the IVS (Cheng et al, 2002;Sharma et al, 2004). Furthermore, ambient hypoxia enhances the expression of the HIF-1-regulated gene VEGF in avian systems (Tomanek et al, 2003).…”

Section: Apoptosis and Hypoxic Tissuesmentioning

confidence: 55%

Apoptosis in the developing mouse heart

Barbosky

Lawrence

Karunamuni

et al. 2006

Developmental Dynamics

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Apoptosis occurs at high frequency in the myocardium of the developing avian cardiac outflow tract (OFT). Upor down-regulating apoptosis results in defects resembling human conotruncal heart anomalies. This finding suggested that regulated levels of apoptosis are critical for normal morphogenesis of the four-chambered heart. Recent evidence supports an important role for hypoxia of the OFT myocardium in regulating cell death and vasculogenesis. The purpose of this study was to determine whether apoptosis in the outflow tract myocardium occurs in the mouse heart during developmental stages comparable to the avian heart and to determine whether differential hypoxia is also present at this site in the murine heart. Apoptosis was detected using a fluorescent vital dye, Lysotracker Red (LTR), in the OFT myocardium of the mouse starting at embryonic day (E) 12.5, peaking at E13.5-14.5, and declining thereafter to low or background levels by E18.5. In addition, high levels of apoptosis were detected in other cardiac regions, including the apices of the ventricles and along the interventricular sulcus. Apoptosis in the myocardium was detected by double-labeling with LTR and cardiomyocyte markers. Terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick endlabeling (TUNEL) and immunostaining for cleaved Caspase-3 were used to confirm the LTR results. At the peak of OFT apoptosis in the mouse, the OFT myocardium was relatively hypoxic, as indicated by specific and intense EF5 staining and HIF1␣ nuclear localization, and was surrounded by the developing vasculature as in the chicken embryo. These findings suggest that cardiomyocyte apoptosis is an evolutionarily conserved mechanism for normal morphogenesis of the outflow tract myocardium in avian and mammalian species.

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“…The last step, involving differentiation and patterning of the arterial and venous parts of the coronary system, occurs after the connection to circulation and is probably in part controlled by the hemodynamic signals from the lumen. Differential hypoxia of the myocardium and subsequent activation of hypoxia-inducible factors such as HIF-1 may play a role in organizing the large vessels of the coronaries at the atrioventricular and interventricular sulci (Wikenheiser et al, 2006). Much of our knowledge about the coronary development comes from studies in the avian systems, in particular the Japanese quail (Coturnix coturnix japonica).…”

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confidence: 99%