Loss of Endothelial Glycocalyx During Normothermic Machine Perfusion of Porcine Kidneys Irrespective of Pressure and Hematocrit

BACKGROUND: Normothermic machine perfusion (NMP) is a promising modality for marginal donor kidneys. However, little is known about the effects of NMP on causing endothelial glycocalyx (eGC) injury. This study aims to evaluate the effects of NMP on eGC injury in marginal donor kidneys and whether this is affected by perfusion pressures and hematocrits.METHODS: Porcine slaughterhouse kidneys (n = 6/group) underwent 35 min of warm ischemia. Thereafter, the kidneys were preserved with oxygenated hypothermic machine perfusion for 3 h. Subsequently, 4 h of NMP was applied using pressure-controlled perfusion with an autologous blood-based solution containing either 12%, 24%, or 36% hematocrit. Pressures of 55, 75, and 95 mm Hg were applied in the 24% group. Perfusate, urine, and biopsy samples were collected to determine both injury and functional parameters.RESULTS: During NMP, hyaluronan levels in the perfusate increased significantly ( P &lt; 0.0001). In addition, the positivity of glyco-stained glycocalyx decreased significantly over time, both in the glomeruli ( P = 0.024) and peritubular capillaries ( P = 0.003). The number of endothelial cells did not change during NMP ( P = 0.157), whereas glomerular endothelial expression of vascular endothelial growth factor receptor-2 decreased significantly ( P &lt; 0.001). Microthrombi formation was significantly increased after NMP. The use of different pressures and hematocrits did not affect functional parameters during perfusion. CONCLUSIONS: NMP is accompanied with eGC and vascular endothelial growth factor receptor-2 loss, without significant loss of endothelial cells. eGC loss was not affected by the different pressures and hematocrits used. It remains unclear whether endothelial injury during NMP has harmful consequences for the transplanted kidney.</p

The Quantity Theory of Money in Historical Perspective

The paper reconstructs the origins of the quantity theory of money and its applications. Against the background of the history of money, it is shown that the theory was flexible enough to adapt to institutional change and thus succeeded in maintaining its relevance. To this day, it is useful as an analytical framework. Although, due to Goodhart's Law, it now has only limited potential to guide monetary policy and was consequently abandoned by most central banks, an empirical analysis drawing on a panel data set covering more than hundred countries from 1991 to the present confirms that the theory still holds: a positive correlation between the excess growth rate of the stock of money and the rate of inflation cannot be rejected. Yet, while the correlation holds for the whole sample, proportionality is driven by a small number of influential observations with very high inflation