Bis maltolato oxovanadium (BMOV) and ischemia/reperfusion-induced acute kidney injury in rats

The aim of the present study was to test the potential protective effects of the organic vanadium salt bis (maltolato) oxovanadium (BMOV; 15 mg/kg) in the context of renal ischemia/reperfusion (30 min of ischemia) and its effects on renal oxygenation and renal function in the acute phase of reperfusion (up to 90 min post-ischemia). Ischemia was established in anesthetized and mechanically ventilated male Wistar rats by renal artery clamping. Renal microvascular and venous oxygenation were measured using phosphorimetry. Creatinine clearance rate, sodium reabsorption, and renal oxygen handling efficiency were considered markers for renal function. The main findings were that BMOV did not affect the systemic and renal hemodynamic and oxygenation variables and partially protected renal sodium reabsorption. Pretreatment with the organic vanadium compound BMOV did not protect the kidney from I/R injur

Evaluation of multi-exponential curve fitting analysis of oxygen-quenched phosphorescence decay traces for recovering microvascular oxygen tension histograms

Although it is generally accepted that oxygen-quenched phosphorescence decay traces can be analyzed using the exponential series method (ESM), its application until now has been limited to a few (patho)physiological studies, probably because the reliability of the recovered oxygen tension (pO2) histograms has never been extensively evaluated and lacks documentation. The aim of this study was, therefore, to evaluate the use of the ESM to adequately determine pO2 histograms from phosphorescence decay traces. For this purpose we simulated decay traces corresponding to uni- and bimodal pO2 distributions and recovered the pO2 histograms at different signal-to-noise ratios (SNRs). Ultimately, we recovered microvascular pO2 histograms measured in the rat kidney in a model of endotoxemic shock and fluid resuscitation and showed that the mean microvascular oxygen tension, 〈pO2〉, decreased after induction of endotoxemia and that after 2 h of fluid resuscitation, 〈pO2〉 remained low, but the hypoxic peak that had arisen during endotoxemia was reduced. This finding illustrates the importance of recovering pO2 histograms under (patho)physiological conditions. In conclusion, this study has characterized how noise affects the recovery of pO2 histograms using the ESM and documented the reliability of the ESM for recovering both low- and high-pO2 distributions for SNRs typically found in experiments. This study might therefore serve as a frame of reference for investigations focused on oxygen (re)distribution during health and disease and encourage researchers to (re-)analyze data obtained in (earlier) studies possibly revealing new insights into complex disease states and treatment strategies

Therapeutic strategies for the protection of renal oxygenation in experimental models of acute kidney injury

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

The impact of storage on red cell function in blood transfusion

Despite the common use of red-blood-cell transfusions in clinical practice, actual beneficial effects of red blood cells have never been demonstrated. On the contrary, several studies suggest that red-blood-cell transfusions are associated with higher risks of morbidity and mortality. The effects of the duration of storage on the efficacy of red blood cells have therefore been questioned in a number of studies. Recent insights into the physiology of red blood cells such as the role of the hypoxia-induced vasodilator-releasing function of red blood cells--is discussed in relation to the controversy surrounding the use of blood transfusions in clinical practic

Blood transfusions recruit the microcirculation during cardiac surgery

Perioperative red blood cell transfusions are commonly used in patients undergoing cardiac surgery to correct anemia caused by blood loss and hemodilution associated with cardiopulmonary bypass circulation. The aim of this investigation was to test the hypothesis that blood transfusion has beneficial effects on sublingual microcirculatory density, perfusion, and oxygenation. To this end, sidestream dark field (SDF) imaging and spectrophotometry were applied sublingually before and after blood transfusion during cardiac surgery. Twenty-four adult patients undergoing on-pump cardiac surgery, including coronary artery bypass grafting, cardiac-valve surgery, or a combination of these two procedures, were included consecutively in this prospective, observational study. Sublingual microcirculatory density and perfusion were assessed using SDF imaging in 12 patients (Group A). Sublingual reflectance spectrophotometry was applied in 12 patients (Group B) to monitor microcirculatory oxygenation and hemoglobin (Hb) concentration. Blood transfusion caused an increase in systemic Hb concentration (p < 0.01) and hematocrit (p < 0.01). At the microcirculatory level, blood transfusion resulted in increased microcirculatory density (from 10.5 ± 1.2 to 12.9 ± 1.2 mm capillary/mm(2) tissue, p < 0.01) as shown using SDF imaging. In concert with the SDF measurements, spectrophotometry showed that microcirculatory Hb content increased from 61.4 ± 5.9 to 70.0 ± 4.7 AU (p < 0.01) and that microcirculatory Hb oxygen saturation increased from 65.6 ± 8.3% to 68.6 ± 8.4% (p = 0.06). In this study we have shown that blood transfusion: 1) improves the systemic circulation and oxygen-carrying capacity, 2) improves sublingual microcirculatory density but not perfusion velocity, and 3) improves microcirculatory oxygen saturatio

L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats

Legrand M, Almac E, Mik EG, Johannes T, Kandil A, Bezemer R, Payen D, Ince C. L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats. Am J Physiol Renal Physiol 296: F1109-F1117, 2009. First published February 18, 2009; doi:10.1152/ajprenal.90371.2008.-Even though renal hypoxia is believed to play a pivotal role in the development of acute kidney injury, no study has specifically addressed the alterations in renal oxygenation in the early onset of renal ischemia-reperfusion (I/R). Renal oxygenation depends on a balance between oxygen supply and consumption, with the nitric oxide (NO) as a major regulator of microvascular oxygen supply and oxygen consumption. The aim of this study was to investigate whether I/R induces inducible NO synthase (iNOS)-dependent early changes in renal oxygenation and the potential benefit of iNOS inhibitors on such alterations. Anesthetized Sprague-Dawley rats underwent a 30-min suprarenal aortic clamping with or without either the nonselective NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) or the selective iNOS inhibitor L-N-6-(1-iminoethyl) lysine hydrochloride (L-NIL). Cortical (C mu Po-2) and outer medullary (M mu Po-2) microvascular oxygen pressure (mu Po-2), renal oxygen delivery (Do(2ren)), renal oxygen consumption ((V) over doto(2ren)), and renal oxygen extraction (O2ER) were measured by oxygen-dependent quenching phosphorescence techniques throughout 2 h of reperfusion. During reperfusion renal arterial resistance and oxygen shunting increased, whereas renal blood flow, C mu Po-2, and M mu Po-2 (-70, -42, and -42%, respectively, P < 0.05), (V) over dot o(2ren), and Do(2ren) (-70%, P < 0.0001, and -28%, P < 0.05) dropped. Whereas L-NAME further decreased Do(2ren), (V) over dot o(2ren), C mu Po-2, and M mu Po-2 and deteriorated renal function, L-NIL partially prevented the drop of Do(2ren) and mu Po-2, increased O2ER, restored (V) over dot o(2ren) and metabolic efficiency, and prevented deterioration of renal function. Our results demonstrate that renal I/R induces early iNOS-dependent microvascular hypoxia in disrupting the balance between microvascular oxygen supply and (V) over dot o(2ren), whereas endothelial NO synthase activity is compulsory for the maintenance of this balance. L-NIL can prevent ischemic-induced renal microvascular hypoxia

L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats

Legrand M, Almac E, Mik EG, Johannes T, Kandil A, Bezemer R, Payen D, Ince C. L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats. Am J Physiol Renal Physiol 296: F1109-F1117, 2009. First published February 18, 2009; doi:10.1152/ajprenal.90371.2008.-Even though renal hypoxia is believed to play a pivotal role in the development of acute kidney injury, no study has specifically addressed the alterations in renal oxygenation in the early onset of renal ischemia-reperfusion (I/R). Renal oxygenation depends on a balance between oxygen supply and consumption, with the nitric oxide (NO) as a major regulator of microvascular oxygen supply and oxygen consumption. The aim of this study was to investigate whether I/R induces inducible NO synthase (iNOS)-dependent early changes in renal oxygenation and the potential benefit of iNOS inhibitors on such alterations. Anesthetized Sprague-Dawley rats underwent a 30-min suprarenal aortic clamping with or without either the nonselective NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) or the selective iNOS inhibitor L-N-6-(1-iminoethyl) lysine hydrochloride (L-NIL). Cortical (C mu Po-2) and outer medullary (M mu Po-2) microvascular oxygen pressure (mu Po-2), renal oxygen delivery (Do(2ren)), renal oxygen consumption ((V) over doto(2ren)), and renal oxygen extraction (O2ER) were measured by oxygen-dependent quenching phosphorescence techniques throughout 2 h of reperfusion. During reperfusion renal arterial resistance and oxygen shunting increased, whereas renal blood flow, C mu Po-2, and M mu Po-2 (-70, -42, and -42%, respectively, P <0.05), (V) over dot o(2ren), and Do(2ren) (-70%, P <0.0001, and -28%, P <0.05) dropped. Whereas L-NAME further decreased Do(2ren), (V) over dot o(2ren), C mu Po-2, and M mu Po-2 and deteriorated renal function, L-NIL partially prevented the drop of Do(2ren) and mu Po-2, increased O2ER, restored (V) over dot o(2ren) and metabolic efficiency, and prevented deterioration of renal function. Our results demonstrate that renal I/R induces early iNOS-dependent microvascular hypoxia in disrupting the balance between microvascular oxygen supply and (V) over dot o(2ren), whereas endothelial NO synthase activity is compulsory for the maintenance of this balance. L-NIL can prevent ischemic-induced renal microvascular hypoxi