Renal Microvascular Oxygenation Research Articles

Impact of sodium glucose linked cotransporter-2 inhibition on renal microvascular oxygen tension in a rodent model of diabetes mellitus.

BackgroundThe mechanisms whereby inhibitors of sodium‐glucose linked cotransporter‐2 (SGLT2) exert their nephroprotective effects in patients with diabetes are incompletely understood but have been hypothesized to include improved tissue oxygen tension within the renal cortex. The impact of SGLT2 inhibition is likely complex and region specific within the kidney. We hypothesize that SGLT2 inhibitors have differential effects on renal tissue oxygen delivery and consumption in specific regions of the diabetic kidney, including the superficial cortex, containing SGLT2‐rich components of proximal tubules, versus the deeper cortex and outer medulla, containing predominantly SGLT1 receptors.MethodsWe measured glomerular filtration rate (GFR), microvascular kidney oxygen tension (PkO2), erythropoietin (EPO) mRNA, and reticulocyte count in diabetic rats (streptozotocin) treated with the SGLT2 inhibitor, dapagliflozin. Utilizing phosphorescence quenching by oxygen and an intravascular oxygen sensitive probe (Oxyphor PdG4); we explored the effects of SGLT2 inhibition on PkO2 in a region‐specific manner, in vivo, in diabetic and non‐diabetic rats. Superficial renal cortical or deeper cortical and outer medullary PkO2 were measured utilizing excitations with blue and red light wavelengths, respectively.ResultsIn diabetic rats treated with dapagliflozin, measurement within the superficial cortex (blue light) demonstrated no change in PkO2. By contrast, measurements in the deeper cortex and outer medulla (red light) demonstrated a significant reduction in PkO2 in dapagliflozin treated diabetic rats (p = 0.014). Consistent with these findings, GFR was decreased, hypoxia‐responsive EPO mRNA levels were elevated and reticulocyte counts were increased with SGLT2 inhibition in diabetic rats (p < 0.05 for all).ConclusionsThese findings indicate that microvascular kidney oxygen tension is maintained in the superficial cortex but reduced in deeper cortical and outer medullary tissue, possibly due to the regional impact of SGLT‐2 inhibition on tissue metabolism. This reduction in deeper PkO2 had biological impact as demonstrated by increased renal EPO mRNA levels and circulating reticulocyte count.

Renal microvascular oxygen tension during hyperoxia and acute hemodilution assessed by phosphorescence quenching and excitation with blue and red light.

The kidney plays a central physiologic role as an oxygen sensor. Nevertheless, the direct mechanism by which this occurs is incompletely understood. We measured renal microvascular partial pressure of oxygen (PkO2) to determine the impact of clinically relevant conditions that acutely change PkO2 including hyperoxia and hemodilution. We utilized two-wavelength excitation (red and blue spectrum) of the intravascular phosphorescent oxygen sensitive probe Oxyphor PdG4 to measure renal tissue PO2 in anesthetized rats (2% isoflurane, n = 6) under two conditions of altered arterial blood oxygen content (CaO2): 1) hyperoxia (fractional inspired oxygen 21%, 30%, and 50%) and 2) acute hemodilutional anemia (baseline, 25% and 50% acute hemodilution). The mean arterial blood pressure (MAP), rectal temperature, arterial blood gases (ABGs), and chemistry (radiometer) were measured under each condition. Blue and red light enabled measurement of PkO2 in the superficial renal cortex and deeper cortical and medullary tissue, respectively. PkO2 was higher in the superficial renal cortex (~ 60 mmHg, blue light) relative to the deeper renal cortex and outer medulla (~ 45 mmHg, red light). Hyperoxia resulted in a proportional increase in PkO2 values while hemodilution decreased microvascular PkO2 in a linear manner in both superficial and deeper regions of the kidney. In both cases (blue and red light), PkO2 correlated with CaO2 but not with MAP. The observed linear relationship between CaO2 and PkO2 shows the biological function of the kidney as a quantitative sensor of anemic hypoxia and hyperoxia. A better understanding of the impact of changes in PkO2 may inform clinical practices to improve renal oxygen delivery and prevent acute kidney injury.

Mycophenolate mofetil improves renal haemodynamics, microvascular oxygenation, and inflammation in a rat model of supra-renal aortic clamping-mediated renal ischaemia reperfusion injury.

Ischaemia/reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), which is characterized by sterile inflammation and oxidative stress. Immune cell activation can provoke overproduction of inflammatory mediators and reactive oxygen species (ROS), leading to perturbation of the microcirculation and tissue oxygenation associated with local and remote tissue injury. This study investigated whether the clinically employed immunosuppressant mycophenolate mofetil (MMF) was able to reduce I/R-induced renal oxygenation defects and oxidative stress by preventing sterile inflammation. Rats were divided into three groups (n=6/group): (1) a sham-operated control group; (2) a group subjected to renal I/R alone (I/R); and (3) a group subjected to I/R and MMF treatment (20mg/kg prior to I/R) (I/R+MMF). Ischaemia was induced by a vascular occluder placed on the abdominal aorta for 30minutes, followed by 120minutes of reperfusion. Renal I/R deteriorated renal oxygenation (P<.001) and oxygen delivery (P<.01), reduced creatinine clearance (P<.01) and tubular sodium reabsorption (P<.001), and increased iNOS, renal tissue injury markers (P<.001), and IL-6 (P<.001). Oral MMF administration prior to insult restored renal cortical oxygenation (P<.05) and iNOS, renal injury markers, and inflammation parameters (P<.001) to near-baseline levels without affecting renal function. MMF exerted a prophylactic effect on renal microvascular oxygenation and abrogated tissue inflammation and renal injury following lower body I/R-induced AKI. These findings may have clinical implications during major vascular or renal transplant surgery.

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

BackgroundThe effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury.MethodsTwenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured.ResultsFluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups.ConclusionsBlood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1581-1) contains supplementary material, which is available to authorized users.

The role of bicarbonate precursors in balanced fluids during haemorrhagic shock with and without compromised liver function

BackgroundLactate, acetate, and gluconate are anions used in balanced resuscitation fluids, of which lactate and acetate are considered bicarbonate precursors. This study investigated the role of the liver in the ability of balanced and unbalanced solutions to correct acid–base alterations and renal haemodynamics and microvascular oxygenation in a rat model of resuscitated haemorrhagic shock. MethodsRinger’s lactate, Ringer’s acetate, PlasmaLyte, or normal saline were administered following haemorrhagic shock in the presence or absence of a 70% partial liver resection. Renal haemodynamics and microvascular oxygenation (by oxygen-dependent quenching of phosphorescence) were measured as well as concentrations of lactate, gluconate, and acetate in plasma and urine. Kidney wet and dry weight was also assessed. ResultsPartial liver resection resulted in increased liver enzymes compared with control and shock groups (P< 0.01). Haemorrhagic shock decreased systemic and renal perfusion and reduced microvascular kidney oxygenation with lactic acidosis (P< 0.01). Resuscitation with balanced fluids did not fully restore renal oxygenation (P< 0.01). Ringer’s acetate and PlasmaLyte increased bicarbonate content and restored pH better than Ringer’s lactate or saline after partial liver resection (P< 0.01). Liver resection caused an increase in plasma gluconate after PlasmaLyte resuscitation (P< 0.05). ConclusionsAcetate-buffered balanced fluids show superior buffering effects compared with Ringer’s lactate or saline. Gluconate is partially metabolized by the liver, although it does not contribute to acid–base control because of its excretion in urine. Acetate is metabolized regardless of liver function and may be the most efficient bicarbonate precursor. Lactate infusion tends to overwhelm the metabolism capacity of the residual liver.

Fully Balanced Fluids do not Improve Microvascular Oxygenation, Acidosis and Renal Function in a Rat Model of Endotoxemia

The expectation of fluid therapy in patients with septic shock is that it corrects hypovolemia, with the aim of restoring tissue perfusion and oxygenation and organ function. This study investigated whether different types of resuscitation fluids were effective in improving renal microcirculatory oxygenation, acidosis, oxidative stress, and renal function in a rat model of endotoxemic shock. Five groups of rats were used: a sham group, a lipopolysaccharide (LPS) group, and three LPS groups that received 30 mL/kg/h of 0.9% sodium chloride (0.9% NaCl), a new bicarbonate buffered crystalloid solution closely resembling the composition of plasma (FB-Cxt) or a hydroxyethyl starch-ringer acetate solution. Systemic hemodynamic variables, renal blood flow, microvascular oxygenation, oxidative/nitrosative stress, and renal function were measured. LPS-induced shock was only partially resolved by fluid administration. Animals became arterially hypotensive despite adequate central venous pressure. Hydroxyethyl starch-ringer acetate was more effective at improving arterial pressures and renal blood flow than 0.9% NaCl or FB-Cxt. Fluids had marginal effects on pH and HCO3 levels irrespective of the buffer, or on renal μPO2 and dysfunction. Colloids increased the markers of renal oxidative stress (P < 0.001), whereas unbalanced crystalloids increased the markers of nitrosative stress during sepsis (P < 0.01). Endotoxemia-induced acidosis and decreases in renal μPO2 or renal injury were not corrected solely by fluid resuscitation, irrespective of the buffer of the fluid. Our study supported the idea that fluids must be supplemented by other compounds that specifically correct renal inflammation and oxygenation to be effective in resolving septic shock-induced renal failure.

Scavenging reactive oxygen species using tempol in the acute phase of renal ischemia/reperfusion and its effects on kidney oxygenation and nitric oxide levels.

BackgroundRenal ischemia/reperfusion (I/R) injury is commonly seen in kidney transplantation and affects the allograft survival rates. We aimed to test our hypothesis that scavenging reactive oxygen species (ROS) with tempol would protect renal oxygenation and nitric oxide (NO) levels in the acute phase of renal I/R.MethodsRats were randomly divided: (1) no I/R, no tempol; (2) no I/R, but with tempol; (3) I/R without tempol; and (4) I/R with tempol. I/R was induced by 30-min clamping of the renal artery. Tempol (200 μmol/kg/h/i.v) was administered 15 min prior to I/R.ResultsI/R without tempol led to a significant decrease in renal oxygen delivery and microvascular oxygenation. Tempol, however, protected renal oxygenation after I/R. At R90, the creatinine clearance rate was lower in the I/R-subjected group that did not receive tempol compared to that in the other groups. I/R injury without tempol treatment led to a significant increase in tissue malondialdehyde levels and a significant decrease in tissue NO levels. Tempol administration before I/R could prevent oxidative stress and altered tissue NO levels.ConclusionsThis underscores that unbalance between oxygen, NO, and ROS forms an important component of the pathogenesis of I/R-induced AKI and should therefore be taken into account when designing a prevention/treatment strategy for renal I/R injury in transplantation.

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

BackgroundThe 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).MethodsIschemia 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.ResultsThe main findings were that BMOV did not affect the systemic and renal hemodynamic and oxygenation variables and partially protected renal sodium reabsorption.ConclusionsPretreatment with the organic vanadium compound BMOV did not protect the kidney from I/R injury.

Activated protein C ameliorates impaired renal microvascular oxygenation and sodium reabsorption in endotoxemic rats.

IntroductionWe aimed to test whether continuous recombinant human activated protein C (APC) administration would be able to protect renal oxygenation and function during endotoxemia in order to provide more insight into the role of coagulation and inflammation in the development of septic acute kidney injury.MethodsIn anesthetized, mechanically ventilated Wistar rats, endotoxemia was induced by lipopolysaccharide administration (10 mg/kg i.v. over 30 min). One hour later, the rats received fluid resuscitation with 0 (LPS + FR group; n = 8), 10 (APC10 group; n = 8), or 100 (APC100 group; n = 8) μg/kg/h APC for 2 h. Renal microvascular oxygenation in the cortex and medulla were measured using phosphorimetry, and renal creatinine clearance rate and sodium reabsorption were measured as indicators of renal function. Statistical significance of differences between groups was tested using two-way ANOVA with Bonferroni post hoc tests.ResultsAPC did not have notable effects on systemic and renal hemodynamic and oxygenation variables or creatinine clearance. The changes in renal microvascular oxygenation in both the cortex (r = 0.66; p < 0.001) and medulla (r = 0.80; p < 0.001) were correlated to renal sodium reabsorption.ConclusionRenal sodium reabsorption is closely correlated to renal microvascular oxygenation during endotoxemia. In this study, fluid resuscitation and APC supplementation were not significantly effective in protecting renal microvascular oxygenation and renal function. The specific mechanisms responsible for these effects of APC warrant further study.Electronic supplementary materialThe online version of this article (doi:10.1186/2197-425X-1-5) contains supplementary material, which is available to authorized users.

Acute Normovolemic Hemodilution in the Pig Is Associated with Renal Tissue Edema, Impaired Renal Microvascular Oxygenation, and Functional Loss

The authors investigated the impact of acute normovolemic hemodilution (ANH) on intrarenal oxygenation and its functional short-term consequences in pigs. Renal microvascular oxygenation (µPO2) was measured in cortex, outer and inner medulla via three implanted optical fibers by oxygen-dependent quenching of phosphorescence. Besides systemic hemodynamics, renal function, histopathology, and hypoxia-inducible factor-1α expression were determined. ANH was performed in n = 18 pigs with either colloids (hydroxyethyl starch 6% 130/0.4) or crystalloids (full electrolyte solution), in three steps from a hematocrit of 30% at baseline to a hematocrit of 15% (H3). ANH with crystalloids decreased µPO2 in cortex and outer medulla approximately by 65% (P < 0.05) and in inner medulla by 30% (P < 0.05) from baseline to H3. In contrast, µPO2 remained unaltered during ANH with colloids. Furthermore, renal function decreased by approximately 45% from baseline to H3 (P < 0.05) only in the crystalloid group. Three times more volume of crystalloids was administered compared with the colloid group. Alterations in systemic and renal regional hemodynamics, oxygen delivery and oxygen consumption during ANH, gave no obvious explanation for the deterioration of µPO2 in the crystalloid group. However, ANH with crystalloids was associated with the highest formation of renal tissue edema and the highest expression of hypoxia-inducible factor-1α, which was mainly localized in distal convoluted tubules. ANH to a hematocrit of 15% statistically significantly impaired µPO2 and renal function in the crystalloid group. Less tissue edema formation and an unimpaired renal µPO2 in the colloid group might account for a preserved renal function.

The Great Fluid Debate

The Great Fluid Debate

The acute effects of acetate-balanced colloid and crystalloid resuscitation on renal oxygenation in a rat model of hemorrhagic shock

IntroductionFluid resuscitation therapy is the initial step of treatment for hemorrhagic shock. In the present study we aimed to investigate the acute effects of acetate-balanced colloid and crystalloid resuscitation on renal oxygenation in a rat model of hemorrhagic shock. We hypothesized that acetate-balanced solutions would be superior in correcting impaired renal perfusion and oxygenation after severe hemorrhage compared to unbalanced solutions. MethodsIn anesthetized, mechanically ventilated rats, hemorrhagic shock was induced by withdrawing blood from the femoral artery until mean arterial pressure (MAP) was reduced to 30mmHg. One hour later, animals were resuscitated with either hydroxyethyl starch (HES, 130/0.42kDa) dissolved in saline (HES-NaCl; n=6) or a acetate-balanced Ringer's solution (HES-RA; n=6), as well as with acetated Ringer's solution (RA; n=6) or 0.9% NaCl alone (NaCl; n=6) until a target MAP of 80mmHg was reached. Oxygen tension in the renal cortex (CμPO2), outer medulla (MμPO2), and renal vein were measured using phosphorimetry. ResultsHemorrhagic shock (MAP=30mmHg) significantly decreased renal oxygenation and oxygen consumption. Restoring the MAP to 80mmHg required 24.8±1.7ml of NaCl, 21.7±1.4ml of RA, 5.9±0.5ml of HES-NaCl (p<0.05 vs. NaCl and RA), and 6.0±0.4ml of HES-RA (p<0.05 vs. NaCl and RA). NaCl, RA, and HES-NaCl resuscitation led to hyperchloremic acidosis, while HES-RA resuscitation did not. Only HES-RA resuscitation could restore renal blood flow back to ∼85% of baseline level (from 1.9±0.1ml/min during shock to 5.1ml±0.2ml/min 60min after HES-RA resuscitation) which was associated with an improved renal oxygenation (CμPO2 increased from 24±2mmHg during shock to 50±2mmHg 60min after HES-RA resuscitation) albeit not to baseline level. At the end of the protocol, creatinine clearance was decreased in all groups with no differences between the different resuscitation groups. ConclusionWhile resuscitation with the NaCl and RA (crystalloid solutions) and the HES-NaCl (unbalanced colloid solution) led to hyperchloremic acidosis, resuscitation with the HES-RA (acetate-balanced colloid solution) did not. The HES-RA was furthermore the only fluid restoring renal blood flow back to ∼85% of baseline level and most prominently improved renal microvascular oxygenation.

Balanced vs unbalanced crystalloid resuscitation in a near-fatal model of hemorrhagic shock and the effects on renal oxygenation, oxidative stress, and inflammation

BackgroundThe aim of the present study was to test the hypothesis that balanced crystalloid resuscitation would be better for the kidney than unbalanced crystalloid resuscitation in a rat hemorrhagic shock model. MethodsMale Wistar rats were randomly assigned to four groups (n=6/group): (1) time control; (2) hemorrhagic shock control; (3) hemorrhagic shock followed by unbalanced crystalloid resuscitation (0.9% NaCl); and (4) hemorrhagic shock followed by acetate and gluconate-balanced crystalloid resuscitation (Plasma Lyte). We tested the solutions for their effects on renal hemodynamics and microvascular oxygenation, strong-ion difference, systemic and renal markers of inflammation and oxidative stress including glycocalyx degradation as well as their effects on renal function. ResultsThe main findings of our study were that: (1) both the balanced and unbalanced crystalloid solutions successfully restored the blood pressure, but renal blood flow was only recovered by the balanced solution although this did not lead to improved renal microvascular oxygenation; (2) while unbalanced crystalloid resuscitation induced hyperchloremia and worsened metabolic acidosis in hemorrhaged rats, balanced crystalloid resuscitation prevented hyperchloremia, restored the acid–base balance, and preserved the anion gap and strong ion difference in these animals; (3) in addition balanced crystalloid resuscitation significantly improved renal oxygen consumption (increased VO2, decreased EFNa+); and (4) however neither balanced nor unbalanced crystalloid resuscitation could normalize systemic inflammation or oxidative stress. Functional immunohistochemistry biomarkers showed improvement in L-FABP in favor of balanced solutions in comparison to the hemorrhagic group although no such benefit was seen for renal tubular injury (measured by NGAL) by giving either unbalanced or balanced solutions. ConclusionsAlthough balanced crystalloid resuscitation seems superior to balanced crystalloid resuscitation in protecting the kidney after hemorrhagic shock and is certainly better than not applying fluid resuscitation, these solutions were not able to correct systemic inflammation or oxidative stress associated with hemorrhagic shock.

The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

PurposeTo study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats.MethodsRats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney.ResultsLPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group.ConclusionsIn our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-011-2267-4) contains supplementary material, which is available to authorized users.

Fluid Resuscitation Does Not Improve Renal Oxygenation during Hemorrhagic Shock in Rats

The resuscitation strategy for hemorrhagic shock remains controversial, with the kidney being especially prone to hypoxia. The authors used a three-phase hemorrhagic shock model to investigate the effects of fluid resuscitation on renal oxygenation. After a 1-h shock phase, rats were randomized into four groups to receive either normal saline or hypertonic saline targeting a mean arterial pressure (MAP) of either 40 or 80 mmHg. After such resuscitation, rats were transfused with the shed blood. Renal macro- and microcirculation were monitored with cortical and outer-medullary microvascular oxygen pressure, renal oxygen delivery, and renal oxygen consumption measured using oxygen-dependent quenching of phosphorescence. Hemorrhagic shock was characterized by a drop of aortic blood flow, MAP, renal blood flow, renal oxygen delivery, renal oxygen consumption, and renal microvascular PO2. During the fluid resuscitation phase, normal saline targeting a MAP = 80 mmHg was the sole strategy able to restore aortic blood flow, renal blood flow, and renal oxygen consumption, although without improving renal oxygen delivery. However, none of the strategies using either normal saline or hypertonic saline or targeting a high MAP could restore the renal microvascular Po2. Blood transfusion increased microvascular Po2 but was unable to totally restore renal microvascular oxygenation to baseline values. This experimental rat study shows that (1) high MAP-directed fluid resuscitation (80 mmHg) does not lead to higher renal microvascular Po2 compared with fluid resuscitation targeted to MAP (40 mmHg); (2) hypertonic saline is not superior to normal saline regarding renal oxygenation; and (3) decreased renal oxygenation persists after blood transfusion.

Rejuvenation of stored human red blood cells reverses the renal microvascular oxygenation deficit in an isovolemic transfusion model in rats

Storage of red blood cells (RBCs) results in various biochemical changes, including a decrease in cellular adenosine triphosphate and 2,3-diphosphoglycerate acid. Previously it was shown that stored human RBCs show a deficit in the oxygenation of the microcirculation in the gut of anesthetized rats. In this study, the effect of RBCs on rat kidney oxygenation and the effect of rejuvenation of stored RBCs on their ability to deliver oxygen were investigated. Washed RBCs, derived from leukoreduced RBCs stored in saline-adenine-glucose-mannitol, were tested in an isovolemic transfusion model in rats after hemodilution until 30 percent hematocrit (Hct). The cells were derived from RBCs stored for up 3 days or from RBCs stored for 5 to 6 weeks with or without incubation in Rejuvesol to rejuvenate the cells. Renal microvascular oxygen concentrations (microPO(2)) were determined by Pd-porphyrin phosphorescence lifetime measurements. Isovolemic transfusion exchange of 5- to 6-week-stored RBCs resulted in a significantly larger decrease in renal microPO(2) than RBCs stored for up to 3 days: 16.1 +/- 2.3 mmHg versus 7.1 +/- 1.5 mmHg, respectively (n = 5). Rejuvenation of stored RBCs completely prevented this deficit in kidney oxygenation. The differences in oxygen delivery were not due to different recoveries of the human RBCs in the rat circulation. This study shows that the storage-induced deficit of human RBCs to oxygenate the rat kidney microcirculation at reduced Hct is completely reversible. Prevention of metabolic changes during storage is therefore a valid approach to prevent this deficit.

Activated protein C restores kidney function in endotoxin-induced acute renal failure in the rat

Activated protein C (APC) has been shown to have beneficial effects on the inflammatory process and coagulation during sepsis. Inflammation and coagulopathy impair the microvasculature and therefore disturb oxygen transport to the tissue. The hypothesis of our study was that APC treatment improves renal microvascular oxygenation and kidney function in endotoxin-induced acute renal failure in the rat.

Acute decrease in renal microvascular Po2 during acute normovolemic hemodilution

Large differences in the tolerance of organ systems to conditions of decreased O(2) delivery such as hemodilution exist. The kidney receives approximately 25% of the cardiac output and O(2) delivery is in excess of the oxygen demand under normal circumstances. In a rat model of acute normovolemic hemodilution (ANH), we studied the effect of reduced hematocrit on renal regional and microvascular oxygenation. Experiments were performed in 12 anesthetized male Wistar rats. Six animals underwent four steps of ANH (hematocrit 25, 15, 10, and <10%). Six animals served as time-matched controls. Systemic and renal hemodynamic and oxygenation parameters were monitored. Renal cortical (c) and outer medullary (m) microvascular PO(2) (microPO(2)) and the renal venous PO(2) (P(rv)O(2)) were continuously measured by oxygen-dependent quenching of phosphorescence. Despite a significant increase in renal blood flow in the first two steps of ANH, cmicroPO(2) and mmicroPO(2) dropped immediately. From the first step onward oxygen consumption (VO(2(ren))) became dependent on oxygen delivery (DO(2(ren))). With a progressive decrease in hematocrit, a significant correlation between microPO(2) and VO(2(ren)) could be observed, as well as a PO(2) gap between microPO(2) and P(rv)O(2). Furthermore, there was a high correlation between VO(2(ren)) and RBF over a wide range of flows. In conclusion, the oxygen supply to the renal tissue is becoming critical already in an early stage of ANH due to the combination of increased VO(2(ren)), decreased DO(2(ren)), and intrarenal O(2) shunt. This has clinical relevance as recent publications reporting that hemodilution during surgery forms a risk factor for postoperative renal dysfunction.

Peritubular control of proximal tubular fluid reabsorption in the rat kidney.

Peritubular control of proximal tubular fluid reabsorption in the rat kidney.