Mitochondrial oxygen tension within the heart

• Published in: Journal of molecular and cellular cardiology Vol. 46; no. 6; pp. 943 - 951
• Main Authors: Mik, Egbert G, Ince, Can, Eerbeek, Otto, Heinen, Andre, Stap, Jan, Hooibrink, Berend, Schumacher, Cees A, Balestra, Gianmarco M, Johannes, Tanja, Beek, Johan F, Nieuwenhuis, Ab F, van Horssen, Pepijn, Spaan, Jos A, Zuurbier, Coert J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2009
• Subjects: Aminolevulinic Acid - pharmacology; Animals; Cardiovascular; Cells, Cultured; Delayed fluorescence; Flow Cytometry; Heart - drug effects; In vivo; Langendorff; Male; Microscopy, Fluorescence; Mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondrial PO 2; Oxygen Consumption - drug effects; Photosensitizing Agents - pharmacology; Protoporphyrin IX; Protoporphyrins - metabolism; Rats; Rats, Wistar; In vivo; Langendorff; Mitochondria; Delayed fluorescence; Protoporphyrin IX; Mitochondrial PO 2
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2009.02.002

Abstract By using a newly developed optical technique which enables non-invasive measurement of mitochondrial oxygenation (mitoPO2 ) in the intact heart, we addressed three long-standing oxygenation questions in cardiac physiology: 1) what is mitoPO2 within the in vivo heart?, 2) is mitoPO2 heterogeneously distributed?, and 3) how does mitoPO2 of the isolated Langendorff-perfused heart compare with that in the in vivo working heart? Following calibration and validation studies of the optical technique in isolated cardiomyocytes, mitochondria and intact hearts, we show that in the in vivo condition mean mitoPO2 was 35 ± 5 mm Hg. The mitoPO2 was highly heterogeneous, with the largest fraction (26%) of mitochondria having a mitoPO2 between 10 and 20 mm Hg, and 10% between 0 and 10 mm Hg. Hypoxic ventilation (10% oxygen) increased the fraction of mitochondria in the 0–10 mm Hg range to 45%, whereas hyperoxic ventilation (100% oxygen) had no major effect on mitoPO2 . For Langendorff-perfused rat hearts, mean mitoPO2 was 29 ± 5 mm Hg with the largest fraction of mitochondria (30%) having a mitoPO2 between 0 and 10 mm Hg. Only in the maximally vasodilated condition, did the isolated heart compare with the in vivo heart (11% of mitochondria between 0 and 10 mm Hg). These data indicate 1) that the mean oxygen tension at the level of the mitochondria within the heart in vivo is higher than generally considered, 2) that mitoPO2 is considerably heterogeneous, and 3) that mitoPO2 of the classic buffer-perfused Langendorff heart is shifted to lower values as compared to the in vivo heart.