- Myocardial microcirculation and mitochondrial energetics in the isolated rat heart
- Award date
- 4 November 2015
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Jesse Ashruf describes how the anatomy of the myocardial microcirculation determines the distribution pattern of oxygen to tissue and mitochondria, as evaluated with NADH- and Pd-porphyrin-videofluori-/phosphorimetry. In normal hearts this pattern reveals so-called weak microcirculatory units, originating at the capillary level, which are the first areas to become ischemic during episodes metabolic or circulatory stress. In hypertrophic Langendorff perfused hearts these weak areas are much larger indicating a disturbance at the arteriolar/arterial level.
Cardiac work causes a decrease in mitochondrial NADH, in contrast to the view that increased mitochondrial respiration is driven by an increase in mitochondrial NADH. An explanation for the observation in some studies that increased work is associated with increased mitochondrial NADH is that increased work in the isolated perfused heart induces local ischemia, because the Langendorff perfused heart is borderline aerobic.
NADH- and Pd-porphyrin-videofluori-/phosphorimetry can also be used to evaluate the mitochondrial redox state and microcirculatory oxygenation in vivo.
Sepsis deteriorates myocardial mitochondrial oxidation, an effect that can be evaluated using NADH-videofluorimetry, making this a promising instrument to study the complex effect of sepsis on (micro-)circulation and mitochondrial function. Further advances in the understanding and treatment of shock must include a component on the (patho-)physiology of the microcirculation since in this functional anatomical compartment the most relevant mechanisms occur that cannot be understood by further advances in macrocirculatory knowledge.
- Research conducted at: Universiteit van Amsterdam
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