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Energy metabolism in the failing right ventricle: Limitations of oxygen delivery and the creatine kinase system

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Energy metabolism in the failing right ventricle : Limitations of oxygen delivery and the creatine kinase system. / Fowler, Ewan D.; Hauton, David; Boyle, John; Egginton, Stuart; Steele, Derek S.; White, Ed.

In: International Journal of Molecular Sciences, Vol. 20, No. 8, 1805, 12.04.2019.

Research output: Contribution to journalArticle

Harvard

Fowler, ED, Hauton, D, Boyle, J, Egginton, S, Steele, DS & White, E 2019, 'Energy metabolism in the failing right ventricle: Limitations of oxygen delivery and the creatine kinase system', International Journal of Molecular Sciences, vol. 20, no. 8, 1805. https://doi.org/10.3390/ijms20081805

APA

Fowler, E. D., Hauton, D., Boyle, J., Egginton, S., Steele, D. S., & White, E. (2019). Energy metabolism in the failing right ventricle: Limitations of oxygen delivery and the creatine kinase system. International Journal of Molecular Sciences, 20(8), [1805]. https://doi.org/10.3390/ijms20081805

Vancouver

Fowler ED, Hauton D, Boyle J, Egginton S, Steele DS, White E. Energy metabolism in the failing right ventricle: Limitations of oxygen delivery and the creatine kinase system. International Journal of Molecular Sciences. 2019 Apr 12;20(8). 1805. https://doi.org/10.3390/ijms20081805

Author

Fowler, Ewan D. ; Hauton, David ; Boyle, John ; Egginton, Stuart ; Steele, Derek S. ; White, Ed. / Energy metabolism in the failing right ventricle : Limitations of oxygen delivery and the creatine kinase system. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 8.

Bibtex

@article{7c1024dd68274dbfb5e032606e143cf1,
title = "Energy metabolism in the failing right ventricle: Limitations of oxygen delivery and the creatine kinase system",
abstract = "Pulmonary arterial hypertension (PAH) results in hypertrophic remodeling of the right ventricle (RV) to overcome increased pulmonary pressure. This increases the O 2 consumption of the myocardium, and without a concomitant increase in energy generation, a mismatch with demand may occur. Eventually, RV function can no longer be sustained, and RV failure occurs. Beta-adrenergic blockers (BB) are thought to improve survival in left heart failure, in part by reducing energy expenditure and hypertrophy, however they are not currently a therapy for PAH. The monocrotaline (MCT) rat model of PAH was used to investigate the consequence of RV failure on myocardial oxygenation and mitochondrial function. A second group of MCT rats was treated daily with the beta-1 blocker metoprolol (MCT + BB). Histology confirmed reduced capillary density and increased capillary supply area without indications of capillary rarefaction in MCT rats. A computer model of O 2 flux was applied to the experimentally recorded capillary locations and predicted a reduction in mean tissue P O2 in MCT rats. The fraction of hypoxic tissue (defined as P O2 < 0.5 mmHg) was reduced following beta-1 blocker (BB) treatment. The functionality of the creatine kinase (CK) energy shuttle was measured in permeabilized RV myocytes by sequential ADP titrations in the presence and absence of creatine. Creatine significantly decreased the K mADP in cells from saline-injected control (CON) rats, but not MCT rats. The difference in K mADP with or without creatine was not different in MCT + BB cells compared to CON or MCT cells. Improved myocardial energetics could contribute to improved survival of PAH with chronic BB treatment.",
keywords = "Beta blocker, Creatine kinase, Heart failure, Monocrotaline, Myocardial hypoxia, Pulmonary artery hypertension, Right ventricle failure",
author = "Fowler, {Ewan D.} and David Hauton and John Boyle and Stuart Egginton and Steele, {Derek S.} and Ed White",
year = "2019",
month = "4",
day = "12",
doi = "10.3390/ijms20081805",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "8",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Energy metabolism in the failing right ventricle

T2 - Limitations of oxygen delivery and the creatine kinase system

AU - Fowler, Ewan D.

AU - Hauton, David

AU - Boyle, John

AU - Egginton, Stuart

AU - Steele, Derek S.

AU - White, Ed

PY - 2019/4/12

Y1 - 2019/4/12

N2 - Pulmonary arterial hypertension (PAH) results in hypertrophic remodeling of the right ventricle (RV) to overcome increased pulmonary pressure. This increases the O 2 consumption of the myocardium, and without a concomitant increase in energy generation, a mismatch with demand may occur. Eventually, RV function can no longer be sustained, and RV failure occurs. Beta-adrenergic blockers (BB) are thought to improve survival in left heart failure, in part by reducing energy expenditure and hypertrophy, however they are not currently a therapy for PAH. The monocrotaline (MCT) rat model of PAH was used to investigate the consequence of RV failure on myocardial oxygenation and mitochondrial function. A second group of MCT rats was treated daily with the beta-1 blocker metoprolol (MCT + BB). Histology confirmed reduced capillary density and increased capillary supply area without indications of capillary rarefaction in MCT rats. A computer model of O 2 flux was applied to the experimentally recorded capillary locations and predicted a reduction in mean tissue P O2 in MCT rats. The fraction of hypoxic tissue (defined as P O2 < 0.5 mmHg) was reduced following beta-1 blocker (BB) treatment. The functionality of the creatine kinase (CK) energy shuttle was measured in permeabilized RV myocytes by sequential ADP titrations in the presence and absence of creatine. Creatine significantly decreased the K mADP in cells from saline-injected control (CON) rats, but not MCT rats. The difference in K mADP with or without creatine was not different in MCT + BB cells compared to CON or MCT cells. Improved myocardial energetics could contribute to improved survival of PAH with chronic BB treatment.

AB - Pulmonary arterial hypertension (PAH) results in hypertrophic remodeling of the right ventricle (RV) to overcome increased pulmonary pressure. This increases the O 2 consumption of the myocardium, and without a concomitant increase in energy generation, a mismatch with demand may occur. Eventually, RV function can no longer be sustained, and RV failure occurs. Beta-adrenergic blockers (BB) are thought to improve survival in left heart failure, in part by reducing energy expenditure and hypertrophy, however they are not currently a therapy for PAH. The monocrotaline (MCT) rat model of PAH was used to investigate the consequence of RV failure on myocardial oxygenation and mitochondrial function. A second group of MCT rats was treated daily with the beta-1 blocker metoprolol (MCT + BB). Histology confirmed reduced capillary density and increased capillary supply area without indications of capillary rarefaction in MCT rats. A computer model of O 2 flux was applied to the experimentally recorded capillary locations and predicted a reduction in mean tissue P O2 in MCT rats. The fraction of hypoxic tissue (defined as P O2 < 0.5 mmHg) was reduced following beta-1 blocker (BB) treatment. The functionality of the creatine kinase (CK) energy shuttle was measured in permeabilized RV myocytes by sequential ADP titrations in the presence and absence of creatine. Creatine significantly decreased the K mADP in cells from saline-injected control (CON) rats, but not MCT rats. The difference in K mADP with or without creatine was not different in MCT + BB cells compared to CON or MCT cells. Improved myocardial energetics could contribute to improved survival of PAH with chronic BB treatment.

KW - Beta blocker

KW - Creatine kinase

KW - Heart failure

KW - Monocrotaline

KW - Myocardial hypoxia

KW - Pulmonary artery hypertension

KW - Right ventricle failure

UR - http://www.scopus.com/inward/record.url?scp=85065294767&partnerID=8YFLogxK

U2 - 10.3390/ijms20081805

DO - 10.3390/ijms20081805

M3 - Article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 8

M1 - 1805

ER -