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Paradoxical arteriole constriction compromises cytosolic and mitochondrial oxygen delivery in the isolated saline-perfused heart.
Am J Physiol Heart Circ Physiol 2018; 315(6):H1791-H1804AJ

Abstract

The isolated saline-perfused heart is used extensively to study cardiac physiology. Previous isolated heart studies have demonstrated lower tissue oxygenation compared with in vivo hearts based on myoglobin oxygenation and the mitochondrial redox state. These data, consistent with small anoxic regions, suggest that the homeostatic balance between work and oxygen delivery is impaired. We hypothesized that these anoxic regions are caused by inadequate local perfusion due to a paradoxical arteriole constriction generated by a disrupted vasoregulatory network. We tested this hypothesis by applying two exogenous vasodilatory agents, adenosine and cromakalim, to relax vascular tone in an isolated, saline-perfused, working rabbit heart. Oxygenation was monitored using differential optical transmission spectroscopy and full spectral fitting. Increases in coronary flow over control with adenosine (27 ± 4 ml/min) or cromakalim (44 ± 4 ml/min) were associated with proportional spectral changes indicative of myoglobin oxygenation and cytochrome oxidase (COX) oxidation, consistent with a decrease in tissue anoxia. Quantitatively, adenosine decreased deoxymyoglobin optical density (OD) across the wall by 0.053 ± 0.008 OD, whereas the reduced form of COX was decreased by 0.039 ± 0.005 OD. Cromakalim was more potent, decreasing deoxymyoglobin and reducing the level of COX by 0.070 ± 0.019 OD and 0.062 ± 0.019 OD, respectively. These effects were not species specific, as Langendorff-perfused mouse hearts treated with adenosine demonstrated similar changes. These data are consistent with paradoxical arteriole constriction as a major source of regional anoxia during saline heart perfusion. We suggest that the vasoregulatory network is disrupted by the washout of interstitial vasoactive metabolites in vitro. NEW & NOTEWORTHY Regional tissue anoxia is a common finding in the ubiquitous saline-perfused heart but is not found in vivo. Noninvasive optical techniques confirmed the presence of regional anoxia under control conditions and demonstrated that anoxia is diminished using exogenous vasodilators. These data are consistent with active arteriole constriction, occurring despite regional anoxia, generated by a disrupted vasoregulatory network. Washout of interstitial vasoactive metabolites may contribute to the disruption of normal vasoregulatory processes in vitro.

Authors+Show Affiliations

Laboratory of Cardiac Energetics, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland.Laboratory of Cardiac Physiology, Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland.Laboratory of Cardiac Energetics, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland.Department of Kinesiology, School of Public Health, University of Maryland , College Park, Maryland.Division of Veterinary Resources, National Institutes of Health , Bethesda, Maryland.Laboratory of Cardiac Energetics, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland.Laboratory of Cardiac Physiology, Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland.Laboratory of Cardiac Energetics, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30311498

Citation

Giles, Abigail V., et al. "Paradoxical Arteriole Constriction Compromises Cytosolic and Mitochondrial Oxygen Delivery in the Isolated Saline-perfused Heart." American Journal of Physiology. Heart and Circulatory Physiology, vol. 315, no. 6, 2018, pp. H1791-H1804.
Giles AV, Sun J, Femnou AN, et al. Paradoxical arteriole constriction compromises cytosolic and mitochondrial oxygen delivery in the isolated saline-perfused heart. Am J Physiol Heart Circ Physiol. 2018;315(6):H1791-H1804.
Giles, A. V., Sun, J., Femnou, A. N., Kuzmiak-Glancy, S., Taylor, J. L., Covian, R., ... Balaban, R. S. (2018). Paradoxical arteriole constriction compromises cytosolic and mitochondrial oxygen delivery in the isolated saline-perfused heart. American Journal of Physiology. Heart and Circulatory Physiology, 315(6), pp. H1791-H1804. doi:10.1152/ajpheart.00493.2018.
Giles AV, et al. Paradoxical Arteriole Constriction Compromises Cytosolic and Mitochondrial Oxygen Delivery in the Isolated Saline-perfused Heart. Am J Physiol Heart Circ Physiol. 2018 12 1;315(6):H1791-H1804. PubMed PMID: 30311498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paradoxical arteriole constriction compromises cytosolic and mitochondrial oxygen delivery in the isolated saline-perfused heart. AU - Giles,Abigail V, AU - Sun,Junhui, AU - Femnou,Armel N, AU - Kuzmiak-Glancy,Sarah, AU - Taylor,Joni L, AU - Covian,Raul, AU - Murphy,Elizabeth, AU - Balaban,Robert S, Y1 - 2018/10/12/ PY - 2018/10/13/pubmed PY - 2019/9/10/medline PY - 2018/10/13/entrez KW - coronary blood flow KW - cytochrome oxidase KW - myoglobin KW - spectral analysis KW - transmission optical spectroscopy SP - H1791 EP - H1804 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 315 IS - 6 N2 - The isolated saline-perfused heart is used extensively to study cardiac physiology. Previous isolated heart studies have demonstrated lower tissue oxygenation compared with in vivo hearts based on myoglobin oxygenation and the mitochondrial redox state. These data, consistent with small anoxic regions, suggest that the homeostatic balance between work and oxygen delivery is impaired. We hypothesized that these anoxic regions are caused by inadequate local perfusion due to a paradoxical arteriole constriction generated by a disrupted vasoregulatory network. We tested this hypothesis by applying two exogenous vasodilatory agents, adenosine and cromakalim, to relax vascular tone in an isolated, saline-perfused, working rabbit heart. Oxygenation was monitored using differential optical transmission spectroscopy and full spectral fitting. Increases in coronary flow over control with adenosine (27 ± 4 ml/min) or cromakalim (44 ± 4 ml/min) were associated with proportional spectral changes indicative of myoglobin oxygenation and cytochrome oxidase (COX) oxidation, consistent with a decrease in tissue anoxia. Quantitatively, adenosine decreased deoxymyoglobin optical density (OD) across the wall by 0.053 ± 0.008 OD, whereas the reduced form of COX was decreased by 0.039 ± 0.005 OD. Cromakalim was more potent, decreasing deoxymyoglobin and reducing the level of COX by 0.070 ± 0.019 OD and 0.062 ± 0.019 OD, respectively. These effects were not species specific, as Langendorff-perfused mouse hearts treated with adenosine demonstrated similar changes. These data are consistent with paradoxical arteriole constriction as a major source of regional anoxia during saline heart perfusion. We suggest that the vasoregulatory network is disrupted by the washout of interstitial vasoactive metabolites in vitro. NEW & NOTEWORTHY Regional tissue anoxia is a common finding in the ubiquitous saline-perfused heart but is not found in vivo. Noninvasive optical techniques confirmed the presence of regional anoxia under control conditions and demonstrated that anoxia is diminished using exogenous vasodilators. These data are consistent with active arteriole constriction, occurring despite regional anoxia, generated by a disrupted vasoregulatory network. Washout of interstitial vasoactive metabolites may contribute to the disruption of normal vasoregulatory processes in vitro. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/30311498/Paradoxical_arteriole_constriction_compromises_cytosolic_and_mitochondrial_oxygen_delivery_in_the_isolated_saline_perfused_heart_ L2 - http://www.physiology.org/doi/full/10.1152/ajpheart.00493.2018?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -