- Therapeutic strategies for the protection of renal oxygenation in experimental models of acute kidney injury
M. van Iterson
- Award date
- 13 November 2014
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
In this thesis, which covers a wide range of pathophysiological models and therapeutic strategies, we have investigated the effects of blood transfusion, fluid resuscitation, and adjuvant drug therapies to protect the kidney from hypoxia and injury. We have first shown that storage of red blood cells (RBCs) leads to an increased rate of hypoxia-induced nitrite reduction to NO and this is associated with increased methemoglobin formation. The increased methemoglobin formation and consequent decrease in oxygen delivery capacity might contribute to the storage-related impairment of aged RBCs to oxygenate the microcirculation. Fluid resuscitation, on the other hand, also has its disadvantages. We have shown that resuscitation with crystalloid solutions and unbalanced colloid solutions leads to hyperchloremic acidosis. However, resuscitation with an acetate-balanced colloid solution did not. This solution could restore renal blood flow back to 85% of baseline level and most prominently improved renal microvascular oxygenation. Furthermore, we have shown that adjuvant therapies, such as inducible NO synthase (iNOS) inhibitors (L-NIL), and to a lesser extend organic vanadium salt BMOV supplementation and activated protein C (APC), may partially protect renal oxygenation and function during endotoxemia, and ischemia/reperfusion (I/R) injury.
- Research conducted at: Universiteit van Amsterdam
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