Divergent Effects of Hypertonic Fluid Resuscitation on Renal Pathophysiological and Structural Parameters in Rat Model of Lower Body Ischemia/Reperfusion-Induced Sterile Inflammation

Abstract

The pathogenesis of acute kidney injury (AKI) is characterized by the deterioration of tissue perfusion and oxygenation and enhanced inflammation. The purpose of this study was to investigate whether or not the hemodynamic and inflammatory effects of hypertonic saline (HS) protect the kidney by promoting renal microcirculatory oxygenation and possible deleterious effects of HS due to its high sodium content on renal functional and structural injury following ischemia/reperfusion. Mechanically ventilated and anesthetized rats were randomly divided into four groups (n = 6 per group): a sham-operated control group; a group subjected to renal ischemia for 45 min by supra-aortic occlusion followed by 2 h of reperfusion (I/R); and I/R group treated with a continuous i.v. infusion (5 mL/kg/h) of either % 0.9 NaCl (IR+NS) or %10 NaCl (I/R+HS) after releasing the clamp. Systemic and renal hemodynamic, renal cortical (CμPO2), and medullar microcirculatory pO2 (MμPO2) are measured by the oxygen-dependent quenching of the phosphorescence lifetime technique. Renal functional, inflammatory, and tissues damage parameters were also assessed. HS, but not NS, treatment restored I/R-induced reduced mean arterial pressure, CμPO2, renal oxygen deliver (DO2ren), and consumption (VO2ren). HS caused a decrease in tubular sodium reabsorption (TNa) that correlated with an elevation of fractional sodium excretion (EFNa) and urine output. HS had an anti-inflammatory effect by reducing the levels TNF-α, IL-6, and hyaluronic acid in the renal tissue samples as compared with the I/R and I/R+NS groups (P < 0.05). HS treatment was also associated with mild acidosis and an increased renal tubular damage. Despite HS resuscitation improving the systemic hemodynamics, microcirculatory oxygenation, and renal oxygen consumption as well as inflammation, it should be limited or strictly controlled for long-term use because of provoking widespread renal structural damage.

Mdivi-1 attenuates oxidative stress and exerts vascular protection in ischemic/hypoxic injury by a mechanism independent of Drp1 GTPase activity

“…Ischemia or hemorrhage refers to a sudden decrease in blood volume and pressure caused by rupture of blood vessels, which may induce anoxic necrosis of multiple organs or even death [ 1 ]. Although treatment of ischemic patients has recently improved owing to fluid resuscitation and correction of acidosis and coagulopathy [ 2 ], vascular dysfunctions such as vascular hyporeactivity following ischemia are still a major cause of death in these subjects [ 3 ]. Vascular hyporeactivity is a severe vascular dysfunction characterized by reduced vascular response to vasoconstrictors, such as norepinephrine (NE), in the treatment of ischemic/hypoxic injury.…”

Furosemide exacerbated the impairment of renal function, oxygenation and medullary damage in a rat model of renal ischemia/reperfusion induced AKI

“…Malondialdehyde (MDA) was quantified using a Quattro Premier XE tandem mass spectrometer (MS/MS, Waters, Milford, Mass) with an Acquity sample manager and an Acquity binary solvent manager [ 16 ]. Nitric oxide levels were measured with chemiluminescence method by the Sievers NO analyzer [ 17 ]. The level of cytokines, MDA, NO and hyaluronan was expressed as per gram of protein (Bradford assay).…”

Kidney Microcirculation as a Target for Innovative Therapies in AKI

“…However, none of the studies related to these compounds focused on promoting renal oxygenation and perfusion to prevent the loss of renal function or damage during I/R-induced AKI. Therefore, in addition to inflammation and oxidative stress, we found that I/R-induced AKI in rats is associated with a low RBF, high renal vascular resistance, and diminished renal oxygenation following a supra-aortic occlusion and two hours of reperfusion [ 95 , 96 , 97 , 107 , 108 ]. Since renal oxygenation depends on a balance between oxygen supply and consumption, for which NO is a major regulator.…”

“…However, both anti-oxidants failed to improve renal oxygen delivery due to low MAP and RBF. In another study, we tested the effect of 10% hypertonic saline resuscitation on renal microcirculation and function and found that it improved MAP, RBF, microcirculatory oxygenation, renal oxygen consumption, glycocalyx integrity, and inflammation but it caused additional tubular damage in I/R-induced AKI [ 107 ].…”