4.6 Article

Endotoxemia decreases matching of regional blood flow and O2 delivery to O2 uptake in the porcine left ventricle

Journal

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00287.2010

Keywords

myocardial depression of sepsis; heterogeneous coronary blood flow; regional oxygen uptake; coronary vasoregulation; isotope labeling; tricarboxylic acid cycle

Funding

  1. Netherlands Heart Foundation [96.127]
  2. Besluit subsidies investeringen kennisinfrastructuur through the Netherlands Genomics Initiative (NGI)
  3. Dutch Government via the NGI [SP 2.2.1]

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Alders DJ, Groeneveld AB, Binsl TW, de Kanter FJ, van Beek JH. Endotoxemia decreases matching of regional blood flow and O-2 delivery to O-2 uptake in the porcine left ventricle. Am J Physiol Heart Circ Physiol 300: H1459-H1466, 2011. First published February 4, 2011; doi:10.1152/ajpheart.00287.2010.-Heterogeneity of regional coronary blood flow is caused in part by heterogeneity in O-2 demand in the normal heart. We investigated whether myocardial O-2 supply/demand mismatching is associated with the myocardial depression of sepsis. Regional blood flow (microspheres) and O-2 uptake ([C-13] acetate infusion and analysis of resultant NMR spectra) were measured in about nine contiguous tissue samples from the left ventricle (LV) in each heart. Endotoxemic pigs (n = 9) showed hypotension at unchanged cardiac output with a fall in LV stroke work and first derivative of LV pressure relative to controls (n = 4). Global coronary blood flow and O-2 delivery were maintained. Lactate accumulated in arterial blood, but net lactate extraction across the coronary bed was unchanged during endotoxemia. When LV O-2 uptake based on blood gas versus NMR data were compared, the correlation was 0.73 (P = 0.007). While stable over time in controls, regional blood flows were strongly redistributed during endotoxin shock, with overall flow heterogeneity unchanged. A stronger redistribution of blood flow with endotoxin was associated with a larger fall in LV function parameters. Moreover, the correlation of regional O-2 delivery to uptake fell from r = 0.73 (P < 0.001) in control to r = 0.18 (P = 0.25, P = 0.009 vs. control) in endotoxemic hearts. The results suggest a redistribution of LV regional coronary blood flow during endotoxin shock in pigs, with regional O-2 delivery mismatched to O-2 demand. Mismatching may underlie, at least in part, the myocardial depression of sepsis.

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