Impaired Myocardial Mitochondrial Function in an Experimental Model of Anaphylactic Shock

Figures

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  Figure 1. Hemodynamic parameters. Time-course of hemodynamic parameters in control (CON, n = 42) and anaphylactic shock (AS, n = 42) groups: (A) abdominal aortic blood flow (ABF), (B) systemic mean arterial pressure (MAP). T0: time of ovalbumin injection. Values are means ± SEM. * The difference in ABF was significantly different between the CON and AS groups at each measurement time (p < 0.01). ** The difference in MAP was significantly different between the CON and AS groups at each measurement time (p < 0.01).

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  Figure 2. Oxidative capacity and activity of respiratory chain complexes in cardiac muscle in CON compared with AS group. CON: control group; AS: anaphylactic shock group; CI: mitochondrial complex I; CI + II: mitochondrial complexes I and II; OXPHOS: mitochondria ADP-activated state of oxidative phosphorylation, CII: mitochondrial complex II. Values are means ± SEM, * p < 0.05.

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  Figure 3. Representative respirometry trace from permeabilized cardiac muscle fibers in the Oxygraph-2 K chambers. Oxygen consumption flux are shown from each chamber. Blue curve indicates oxygen flux in chamber A (control group, CON), and red curve indicates oxygen flux in chamber B (shocked group, AS). Both chambers operated simultaneously. Substrates and inhibitors were sequentially added to each chamber (arrows) to evaluate activity of mitochondrial complexes. Representative areas of each oxygen flux were separated to indicate mitochondroal respiration state (below the figure). CI: complex I; CI + II: complexes I and II; CII: complex II; OXPHOS: oxidative phosphorylation; ROX state: residual oxygen consumption state.

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  Figure 4. Oxidative stress and damage after AS. Myocardial mitochondrial oxidative stress 15 min after AS onset with ROS production (A) was not significantly increased (p = 0.62), and RNS production (B) tended to increase (p = 0.07) in AS group. SODs activity (C) was significantly increased in AS group, which might explain the low rate of ROS in AS group. TBARs concentration (D) was significantly increased in AS group probably due to RNS-pathway with peroxynitrite. Results were expressed as mean ± SEM. * p < 0.05 compared to CON group. CON: control group, AS: shock group, ROS: reactive oxygen species, RNS: reactive nitrogen species, SODs: superoxide dismutases.

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  Figure 5. Representative TEM images of cardiomyocytes (×20k magnification) in CON and AS groups. No obvious changes were observed between groups in mitochondrial shapes (M), mitochondrial membrane (MM), and cristae (C).

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  Figure 6. Illustration of anaphylaxis–suspected pathophysiological mechanisms involving myocardial mitochondrial dysfunction leading at least in part of cardiac dysfunction described in AS. In this study, AS leads to mitochondrial respiration impairment at T15 min in non-phosphorylating respiration with complex II and in maximum OXPHOS activity, which might alter cardiac function. AS-induced oxidative stress leads to oxidative damage with an increase in lipid peroxidation that might similarly impair cardiac function probably through NO-pathway, and its nitrative species as peroxynitrite, and less through ROS because of scavenging by the increase in SODs activity. Complete arrows: relationship based on results of this study. Dotted arrows: relationships based on the literature.