The effects of recruitment of renal functional reserve on renal cortical and medullary oxygenation in non-anesthetized sheep

Aim

Recruitment of renal functional reserve (RFR) with amino acid loading increases renal blood flow and glomerular filtration rate. However, its effects on renal cortical and medullary oxygenation have not been determined. Accordingly, we tested the effects of recruitment of RFR on renal cortical and medullary oxygenation in non-anesthetized sheep.

Methods

Under general anesthesia, we instrumented 10 sheep to enable subsequent continuous measurements of systemic and renal hemodynamics, renal oxygen delivery and consumption, and cortical and medullary tissue oxygen tension (PO₂). We then measured the effects of recruitment of RFR with an intravenous infusion of 500 ml of a clinically used amino acid solution (10% Synthamin® 17) in the non-anesthetized state.

Results

Compared with baseline, Synthamin® 17 infusion significantly increased renal oxygen delivery mean ± SD maximum increase: (from 0.79 ± 0.17 to 1.06 ± 0.16 ml/kg/min, p < 0.001), renal oxygen consumption (from 0.08 ± 0.01 to 0.15 ± 0.02 ml/kg/min, p < 0.001), and glomerular filtration rate (+45.2 ± 2.7%, p < 0.001). Renal cortical tissue PO₂ increased by a maximum of 26.4 ± 1.1% (p = 0.001) and medullary tissue PO₂ increased by a maximum of 23.9 ± 2.8% (p = 0. 001).

Conclusions

In non-anesthetized healthy sheep, recruitment of RFR improved renal cortical and medullary oxygenation. These observations might have implications for the use of recruitment of RFR for diagnostic and therapeutic purposes.     

Phosphate and cyclic AMP excretion decreases during less than 12 hours of hypoxia in conscious rats

Hypocapnia is known to have an antiphosphaturic effect that overcomes the phosphaturic effect of hypoxia. The objective of this study was to examine whether conscious rats exposed to acute hypoxia show a decrease in phosphate excretion due to the concomitant hypocapnia. Wistar rats weighing 200 g were exposed to hypoxia (inspired oxygen fraction=0.10) or normoxia (inspired oxygen fraction=0.21) for 6 h; and rats were alternately exposed to hypoxia or normoxia every 12 h for a total 36 h. Renal clearance and hormone studies were performed. Rats exposed to 6 h of hypoxia (n = 11) showed significant hypophosphaturia and decreases in absolute and fractional excretion of phosphate (0.38±0.10 μg min^-1, mean ±SE, P<0.0001 and 0.59±0.15%, P<0.0001) as compared with normoxic rats (n = 11, 3.91±0.68 μg min-¹ and 5.62±0.85%). In addition, nephrogenous adenosine 3′,5′-cyclic monophosphate level per glomerular filtrate was significantly decreased (-0.87±0.64 nmol dL GF^-1, P<0.05) and plasma parathyroid hormone level was unchanged (45.2±9.5 pg mL-¹) after 6 h of hypoxia as compared with normoxic rats (4.03±1.83 nmol dL GF-¹ and 54.3±10.4 pg mL-¹). A parallel increase in urinary noradrenaline and a decrease in dopamine excretion was observed in rats after 6 h of hypoxia. The decreased phosphate and adenosine 3′,5′-cyclic monophosphate excretion during acute hypoxia were restored to normoxic levels by reoxygenation with 21% oxygen in the study of 12-h intermittent hypoxia. In summary, (1) hypoxia produced by inhalation of 10% oxygen for 12 h or less causes reduced phosphate and adenosine 3′,5′-cyclic monophosphate (cAMP) excretion by spontaneously breathing rats; (2) these effects are reversed by reoxygenation and (3) hypoxia elicits a parallel increase in noradrenaline excretion and a decrease in dopamine excretion. These data suggest that renal adrenergic and dopaminergic systems play important roles in hypophosphaturia during acute hypoxia in conscious rats.     

Acute kidney injury applying pRifle scale in Children of Hospital Universitario del Valle in Cali,Colombia: clinical features,management and evolution

Objective:

To know the epidemiology of Acute Kidney Injury (AKI) in the pediatric population at Hospital Universitario del Valle (HUV), a tertiary University Hospital in Cali, Colombia.

Methods:

We obtained a series of cases through daily surveillance for a seven-month period (June 1 to December 31, 2009) in patients older than 30 days and under 18 years at HUV. We excluded patients with previous diagnosis of chronic renal failure. The new pRIFLE scale was used to define AKI.

Results:

27 patients were detected, with mean age of 36 months. Incidence of AKI was 0.38% from pediatric admissions and 6.2% from the pediatric intensive care unit (pICU) admissions. The pRIFLE scale at study entrance was: Risk: 2 patients, Injury: 8, Failure: 17. Etiology of AKI was: pre-renal in 89%, primary renal disease in 3.7%, and post-renal in 7.4%. There was an association of AKI with sepsis in 66.7% and 48.2% progressed to septic shock. Six patients required renal replacement therapy, all required peritoneal dialysis. The AKI was multi-factorial in 59.3% and associated with systemic multi-organ failure in 59.3%. At study entry, 63% patients were in pICU. The average hospital stay was 21.3 ± 9.2 days. Six children died, 16 resolved AKI, and nine were left with renal sequelae.

Conclusions:

We recommended pRIFLE scale for early diagnosis of AKI in all pediatric services. Education in pRIFLE scale, prevention of AKI, and early management of sepsis and hypovolemia is recommended.     

Lack of contribution of P2X receptors to neurally mediated vasoconstriction in the rabbit kidney in vivo

Aim: The contribution of adenosine triphosphate (ATP) to the neural control of regional renal perfusion in vivo remains unknown. We therefore examined whether P2X receptors mediate renal vascular responses to electrical stimulation of the renal nerves (RNS) in pentobarbitone anaesthetized rabbits. Methods: Responses to RNS were tested before and during renal arterial infusion of α,β‐methylene ATP (α,β‐mATP, 7–56 μg kg⁻¹ min⁻¹) to desensitize P2X₁ receptors. RNS consisted of 3 min trains at graded frequencies and short trains of RNS (4–32 pulses). Results: Three‐minute trains of RNS reduced renal blood flow (RBF), cortical laser Doppler flux (CLDF), and medullary LDF (MLDF) by −90 ± 3%, −89 ± 3% and −31 ± 11%, respectively, at 4 Hz. MLDF was reduced less than CLDF or RBF. During short train RNS, RBF, CLDF and MLDF were reduced by −22 ± 2%, −15 ± 2% and −12 ± 2%, respectively, for 32 s at 1 Hz. CLDF and MLDF were reduced to a similar extent. Infusion of α,β‐mATP induced transient reductions in RBF, CLDF and MLDF, but within 5 min these variables had recovered to control levels. Vascular responses to RNS were not significantly altered by α,β‐mATP treatment. Conclusions: In the rabbit kidney in vivo, α,β‐mATP‐sensitive receptors mediate vasoconstriction and reduce perfusion in both cortical and medullary vascular beds. However, these receptors do not mediate neurally induced reductions in renal perfusion.     

Effects of ATP on rat renal haemodynamics and excretion: role of sodium intake, nitric oxide and cytochrome P450

Aim: Adenosine‐5′‐triphosphate (ATP) affects intrarenal vascular tone and tubular transport via P2 receptors; however, the actual role of the system in regulation of renal perfusion and excretion remains unclear and is the subject of this whole‐kidney study. Methods: Effects of suprarenal aortic ATP infusion, 0.6–1.2 mg kg⁻¹ h⁻¹, were examined in anaesthetised rats maintained on low‐ (LS) or high‐sodium (HS) diet. Renal artery blood flow (RBF, transonic flow probe) and the perfusion (laser‐Doppler flux) of the superficial cortex (CBF) and outer and inner medulla (OM–BF, IM–BF) were measured, together with sodium and water excretion and urine osmolality. Results: Adenosine‐5′‐triphosphate did not change arterial pressure, RBF or CBF while the effects on medullary perfusion depended on sodium intake. In LS rats ATP increased IM–BF 19 ± 6%, the effect was prevented by inhibition of nitric oxide (NO) with N‐nitro‐l ‐arginine methyl ester. In HS rats ATP decreased OM–BF 16 ± 3% and IM–BF (7 ± 4%, not significant); previous inhibition of cytochrome P450 with 1‐aminobenzotriazol blunted the OM–BF decrease and reversed the previous decrease of IM–BF to a 13 ± 8% increase. Inhibition of P2 receptors with pyridoxal derivative (PPADS) abolished medullary vascular responses to ATP. In HS rats pre‐treated with PPADS, ATP increased tubular reabsorption, probably via adenosine formation and stimulation of P1 receptors. Conclusion: The data indicate a potential role of ATP in the selective control of renal medullary perfusion, different in sodium depleted and sodium replete rats. The action of ATP appears to be mediated by the NO system and the cytochrome P450 dependent vasoactive metabolites.     

Thermoregulation of Tuvan pastoralists and Western Europeans during cold exposure

Objectives

This study compared the metabolic and vascular responses, to whole-body and finger cold exposure, of a traditional population lifelong exposed to extreme cold winters with Western Europeans.

Methods

Thirteen cold acclimatized Tuvan pastoralist adults (45 ± 9 years; 24.1 ± 3.2 kg/m²) and 13 matched Western European controls (43 ± 15 years; 22.6 ± 1.4 kg/m²) completed a whole-body cold (10°C) air exposure test and a cold-induced vasodilation (CIVD) test, which involved the immersion of the middle finger into ice-water for 30 min.

Results

During the whole-body cold exposure, the durations until the onset of shivering for three monitored skeletal muscles were similar for both groups. Cold exposure increased the Tuvans' energy expenditure by (mean ± SD) 0.9 ± 0.7 kJ min⁻¹ and the Europeans' by 1.3 ± 1.54 kJ min⁻¹; these changes were not significantly different. The forearm-fingertip skin temperature gradient of the Tuvans was lower, indicating less vasoconstriction, than the Europeans during the cold exposure (0 ± 4.5°C vs. 8.8 ± 2.7°C). A CIVD response occurred in 92% of the Tuvans and 36% of the Europeans. In line, finger temperature during the CIVD test was higher in the Tuvans than the Europeans (13.4 ± 3.4°C vs. 3.9 ± 2.3°C).

Conclusion

Cold-induced thermogenesis and the onset of shivering were similar in both populations. However, vasoconstriction at the extremities was reduced in the Tuvans compared to the Europeans. The enhanced blood flow to the extremities could be beneficial for living in an extreme cold environment by improving dexterity, comfort, and reducing the risk of cold-injuries.     

Renal endothelin system and excretory function in Wistar-Kyoto and Long-Evans rats

Aim: The role of the kidney endothelin system in the renal regulation of fluid and electrolyte excretion was investigated in Wistar–Kyoto (WKY) and Long–Evans (LE) rats in which we found previously marked differences in the renal excretory responses to endothelin A receptor blockade. Methods: The selective endothelin A and B receptor antagonists BQ‐123 (16.4 nmol kg⁻¹ min⁻¹) and BQ‐788 (25 nmol kg⁻¹ min⁻¹) were infused i.v. for 50 min in conscious chronically instrumented WKY and LE rats and their renal function and renal endothelin system were studied. Results: Without effects on glomerular filtration rate or renal blood flow, BQ‐123 and BQ‐788 decreased by more than 50% (P < 0.01) both urine flow rate and electrolyte excretion in WKY rats but only urine flow rate (P < 0.05) in LE rats. Endothelin‐1 content, preproET‐1/GPDH mRNA ratio, B_max and K_d of total endothelin receptors in renal cortex did not differ between the two strains. In contrast, plasma endothelin‐1 concentration (0.58 ± 0.04 vs. 1.05 ± 0.01 femtomol mL⁻¹; P < 0.01), renal papillary ET‐1 concentration (68 ± 5 vs. 478 ± 62 fmol mg⁻¹ protein; P < 0.01) and preproET‐1/GPDH mRNA ratio (0.65 ± 0.09 vs. 0.88 ± 0.05; P < 0.05) as well as total endothelin receptor number in renal papilla (B_max 5.3 ± 0.4 vs. and 9.0 ± 1.2 pmol mg⁻¹ protein; P < 0.05) were markedly lower in LE than in WKY rats. In vitro studies showed that in both strains ET_B receptors on renal cortical membranes amounted between 65% and 67% and on papillary membranes between 85% and 88%. Conclusion: The present data show that the selective ET_A or ET_B receptor blockade differentially affects tubular water and salt handling, which becomes apparent in conditions of low renal papillary endothelin receptor number and tissue endothelin‐1 concentration.     

Retrograde blood flow in the inactive limb is enhanced during constant-load leg cycling in hypoxia

Purpose

This study aimed to elucidate the effects of hypoxia on the pattern of oscillatory blood flow in the inactive limb during constant-load dynamic exercise. We hypothesised that retrograde blood flow in the brachial artery of the inactive limb would increase during constant-load leg cycling under hypoxic conditions.

Methods

Three maximal exercise tests were conducted in eight healthy males on a semi-recumbent cycle ergometer while the subjects breathed a normoxic [inspired oxygen fraction (FIO₂) = 0.209] or two hypoxic gas mixtures (FIO₂ = 0.155 and 0.120). Subjects then performed submaximal exercise at the same relative exercise intensity of 60 % peak oxygen uptake under normoxic or the two hypoxic conditions for 30 min. Brachial artery blood velocity and diameter were recorded simultaneously during submaximal exercise using Doppler ultrasonography.

Results

Antegrade blood flow gradually increased during exercise, with no significant differences among the three trials. Retrograde blood flow showed a biphasic response, with an initial increase followed by a gradual decrease during normoxic exercise. In contrast, retrograde blood flow significantly increased during moderate and severe hypoxic exercise, and remained elevated above normoxic conditions during exercise. At 30 min of exercise, the magnitude of the change in retrograde blood flow during exercise was greater as the level of hypoxia increased (normoxia: ?18.7 ± 23.5 ml min^?1; moderate hypoxia: ?39.3 ± 21.4 ml min^?1; severe hypoxia: ?64.0 ± 36.3 ml min^?1).

Conclusion

These results indicate that moderate and severe hypoxia augment retrograde blood flow in the inactive limb during constant-load dynamic leg exercise.     

Erythropoietin response to acute hypobaric or anaemic hypoxia in gentamicin-administered rats

In an attempt to assess the erythropoietin (Epo) production site(s) in rat kidney, Epo response to hypoxia and renal histopathological changes were studied in rats administered with graded doses of gentamicin. Male Sprague-Dawley rats of 9 to 11 weeks old were used. Following a 14-day subcutaneous administration (67.5 or 33.8 mg kg^-1 day^-1) of gentamicin, a nephrotoxic aminoglycoside, selective proximal tubular lesions were produced. These gentamicin-administered rats were compared with normal rats with respect to Epo response to hypoxia. Two different kinds of hypoxic load, either 0.35 atm hypobaric hypoxia (P_IO2= 46 torr) or acute anaemia (Ht: 29.3 ± 0.2% and [Hb]: 9.7 ± 0.3 g dl^-1) by withdrawing of blood corresponding to 1–2% of body weight was used. During the hypoxic period of up to 48 h, the peak renal venous plasma Epo titres of 3.1 ± 0.6 and 4.3 ± 0.6 U ml^-1 was observed at the 6th h in normal hypobaric hypoxic and anaemic rats, compared with the prehypoxic value of 0.7 ± 0.1 U ml^-1. The Epo titres then declined gradually. In the rats which were administered gentamicin, Epo response pattern was the same as that observed in the normal rats, but the peak value decreased significantly to 0.8 ± 0.3 and 1.1 ± 0.4 U ml^-1 in hypoxic and anaemic rats (P < 0.05). Histological examination revealed the selective damage to renal proximal convoluted tubules. The Epo response was reduced by the tissue damages, and restoration of the gentamicin-induced tissue injury was accompanied with restored Epo response to hypoxia. The results suggest that renal proximal convoluted tubules are involved in Epo production under hypoxia.     

The regulation of blood perfusion in the renal cortex and medulla by reactive oxygen species and nitric oxide in the anaesthetised rat

Aims: The regulation of blood flow through the renal medulla is important in determining blood pressure, and its dysregulation in pathophysiological states, such as oxidative stress, may contribute to the development of hypertension. This investigation examined the hypothesis that reactive oxygen species has both direct and indirect actions, via scavenging NO, to determine the degree of blood perfusion through the renal medulla. Methods: Groups of male Wistar rats received a renal interstitial infusion of either tempol, a superoxide dismutase (SOD) mimetic, or tempol plus catalase (tem + cat), or diethyldithio‐carbamic acid (DETC) a SOD inhibitor, or L‐NAME alone or L‐NAME followed by DETC. Results: Medullary blood perfusion (MBP) increased by 16 ± 1% (P < 0.05) following the renal infusion of tempol and by 35 ± 4%% (P < 0.05) when tem + cat was infused. Cortical blood perfusion (CBP) was unchanged during the administration of tempol and tem + cat. The renal interstitial infusion of DETC reduced CBP by 13 ± 2%, (P < 0.05) and MBP by 22 ± 3% (P < 0.05). Infusion of L‐NAME to block NOS did not change CBP but decreased MBP by 12 ± 4%, which was (P < 0.05) less than the reduction obtained with DETC. Administration of DETC in the presence of L‐NAME reduced CBP and MBP by 17 and 14%, respectively, the latter response being approximately half that obtained when only DETC was infused. Conclusions: These findings demonstrated that both reactive oxygen species and NO determined the level of MBP. The findings support the hypothesis that reactive oxygen species can act both indirectly, via scavenging of NO, and directly via H₂O₂ to modulate blood perfusion in the medulla.     

Opioid μ-receptors in the rostral medullary raphe modulate hypoxia-induced hyperpnea in unanesthetized rats

Aim: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid μ‐receptors have been found in the MR, we studied the putative role of opioid μ‐receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. Methods: We measured pulmonary ventilation () and the body temperatures (Tb) of male Wistar rats before and after the selective opioid μ‐receptor antagonist CTAP (d ‐Phe‐Cys‐Tyr‐d ‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2, cyclic, 0.1 μg per 0.1 μL) was microinjected into the rMR during normoxia or after 60 min of hypoxia. Results: The animals treated with intra‐rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia (430 ± 86 mL kg^?1 min^?1) compared with the control group (790 ± 82 mL kg^?1 min^?1) (P < 0.05). No differences in the Tb were observed between groups during hypoxia. Conclusion: These data suggest that opioids acting on μ‐receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.     

Increased FXYD1 and PGC‐1α mRNA after blood flow‐restricted running is related to fibre type‐specific AMPK signalling and oxidative stress in human muscle

Aim

This study explored the effects of blood flow restriction (BFR) on mRNA responses of PGC‐1α (total, 1α1, and 1α4) and Na⁺,K⁺‐ATPase isoforms (NKA; α_1‐3, β_1‐3, and FXYD1) to an interval running session and determined whether these effects were related to increased oxidative stress, hypoxia, and fibre type‐specific AMPK and CaMKII signalling, in human skeletal muscle.

Methods

In a randomized, crossover fashion, 8 healthy men (26 ± 5 year and 57.4 ± 6.3 mL kg^?1 min^?1) completed 3 exercise sessions: without (CON) or with blood flow restriction (BFR), or in systemic hypoxia (HYP, ~3250 m). A muscle sample was collected before (Pre) and after exercise (+0 hour, +3 hours) to quantify mRNA, indicators of oxidative stress (HSP27 protein in type I and II fibres, and catalase and HSP70 mRNA), metabolites, and α‐AMPK Thr¹⁷²/α‐AMPK, ACC Ser²²¹/ACC, CaMKII Thr²⁸⁷/CaMKII, and PLBSer¹⁶/PLB ratios in type I and II fibres.

Results

Muscle hypoxia (assessed by near‐infrared spectroscopy) was matched between BFR and HYP, which was higher than CON (~90% vs ~70%; P < .05). The mRNA levels of FXYD1 and PGC‐1α isoforms (1α1 and 1α4) increased in BFR only (P < .05) and were associated with increases in indicators of oxidative stress and type I fibre ACC Ser²²¹/ACC ratio, but dissociated from muscle hypoxia, lactate, and CaMKII signalling.

Conclusion

Blood flow restriction augmented exercise‐induced increases in muscle FXYD1 and PGC‐1α mRNA in men. This effect was related to increased oxidative stress and fibre type‐dependent AMPK signalling, but unrelated to the severity of muscle hypoxia, lactate accumulation, and modulation of fibre type‐specific CaMKII signalling.

     

Inhibition of histamine release from human FcεRI+ cells by nimesulide

We have previously demonstrated that pharmacological concentrations of non-steroidal anti-inflammatory drugs (NSAID) such as indomethacin, acetylsalicylic acid, and meclofenamic acid enhance IgE-mediated histamine release (HR) from human basophils. We have now examined the effects of nimesulide (NIM), a new NSAID, on mediator release from human basophils. Preincubation (10 min at 37°C) of basophils with pharmacological concentrations (10⁻⁶−10⁻³ M) of NIM resulted in a concentration-dependent decrease of HR induced by anti-IgE, the Ca²⁺-ionophore A23187 and the formylated tripeptide f-Met-Leu-Phe (FMLP). Maximal inhibition of anti-IgE-induced HR was achieved after preincubation with 10⁻⁴ M NIM and ranged between 14.5% and 44.5% (mean±SEM, 29.7±4.5%). The drug had a marked inhibitory effect on HR from basophils induced by A23187 (80.6±5.5%), FMLP (63.5±10.3%), 12-O-tetradecanoyl-phorbol-13-acetate (57.0±8.7%) and bryostatin 1 (65.7±7.6%). NIM also inhibited the IgE-mediated synthesis of peptide leukotriene C₄ from basophils.

     

Acute kidney injury after trauma: Prevalence, clinical characteristics and RIFLE classification

Background:

Acute kidney injury (AKI) is an uncommon but serious complication after trauma. The objective of this study was to evaluate the prevalence, clinical characteristics and outcome of AKI after trauma.

Patients and Methods:

This was a retrospective study performed from January 2006 to January 2008 in an emergency specialized hospital in Fortaleza city, northeast of Brazil. All patients with AKI admitted in the study period were included. Prevalence of AKI, clinical characteristics and outcome were investigated.

Results:

Of the 129 patients admitted to the intensive care unit (ICU), 52 had AKI. The mean age was 30.1 ± 19.2 years, and 79.8% were males. The main causes of AKI were sepsis in 27 cases (52%) and hypotension in 18 (34%). Oliguria was observed in 33 cases (63%). Dialysis was required for 19 patients (36.5%). Independent risk factors associated with AKI were abdominal trauma [odds ratio (OR) = 3.66, P = 0.027] and use of furosemide (OR = 4.10, P = 0.026). Patients were classified according to RIFLE criteria as Risk in 12 cases (23%), Injury in 13 (25%), Failure in 24 (46%), Loss in 1 (2%) and End-stage in 2 (4%). Overall in-hospital mortality was 95.3%. The main cause of death was sepsis (24%). Mortality was 100% among patients with AKI.

Conclusions:

AKI is a fatal complication after trauma, which presented with a high mortality in the studied population. A better comprehension of factors associated with death in trauma-associated AKI is important, and more effective measures of prevention and treatment of AKI in this population are urgently needed.     

Lung inflammation is induced by renal ischemia and reperfusion injury as part of the systemic inflammatory syndrome

Introduction

Ischemia and reperfusion injury (IRI) are mainly caused by leukocyte activation, endothelial dysfunction and production of reactive oxygen species. Moreover, IRI can lead to a systemic response affecting distant organs, such as the lungs.

Aim

The objective was to study the pulmonary inflammatory systemic response after renal IRI.

Methods

Male C57Bl/6 mice were subjected to 45 min of bilateral renal ischemia, followed by 4, 6, 12, 24 and 48 h of reperfusion. Blood was collected to measure serum creatinine and cytokine concentrations. Bronchoalveolar lavage fluid (BALF) was collected to determine the number of cells and PGE₂ concentration. Expressions of iNOS and COX-2 in lung were determined by Western blot. Gene analyses were quantified by real time PCR.

Results

Serum creatinine increased in the IRI group compared to sham mainly at 24 h after IRI (2.57 ± 0.16 vs. 0.43 ± 0.07, p < 0.01). The total number of cells in BAL fluid was higher in the IRI group in comparison with sham, 12 h (100 × 10⁴ ± 15.63 vs. 18.1×10⁴ ± 10.5, p < 0.05) 24 h (124 × 10⁴ ± 8.94 vs. 23.2×10⁴ ± 3.5, p < 0.05) and 48 h (79 × 10⁴ ± 15.72 vs. 22.2 × 10⁴ ± 4.2, p < 0.05), mainly by mononuclear cells and neutrophils. Pulmonary COX-2 and iNOS were up-regulated in the IRI group. TNF-α, IL-1β, MCP-1, KC and IL-6 mRNA expression were up-regulated in kidney and lungs 24 h after renal IRI. ICAM-1 mRNA was up-regulated in lungs 24 h after renal IRI. Serum TNF-α, IL-1β and MCP-1 and BALF PGE₂ concentrations were increased 24 h after renal IRI.

Conclusion

Renal IRI induces an increase of cellular infiltration, up-regulation of COX-2, iNOS and ICAM-1, enhanced chemokine expression and a Th1 cytokine profile in lung demonstrating that the inflammatory response is indeed systemic, possibly leading to an amplification of renal injury.     

Quantitative BOLD response of the renal medulla to hyperoxic challenge at 1.5 T and 3.0 T

The aim of this study was to gage the magnitude of changes of the apparent renal medullary transverse relaxation time (ΔT₂*) induced by inhalation of pure oxygen (O₂) or carbogen (95% O₂, 5% CO₂) versus baseline breathing of room air. Eight healthy volunteers underwent 2D multi‐gradient echo MR imaging at 1.5 T and 3.0 T. Parametrical T₂* relaxation time maps were computed and average T₂* was measured in regions of interest placed in the renal medulla and cortex. The largest T₂* changes were measured in the renal medulla, with a relative ?T₂* of 33.8 ± 22.0% (right medulla) and 34.7 ± 17.6% (left medulla) as compared to room air for oxygen breathing (p > 0.01), and 53.8 ± 23.9% and 53.5 ± 33.9% (p < 0.01) for carbogen breathing, respectively at 3 T. At 1.5 T, the corresponding values were 13.7 ± 18.5% and 24.1 ± 17.1% (p < 0.01) for oxygen breathing and 23.9 ± 17.2% and 38.9 ± 37.6% (p < 0.01) for carbogen breathing. As a result, we showed that renal medullary T₂* times responded strongly to inhalation of hyperoxic gases, which may be attributed to the hypoxic condition of the medulla and subsequent reduction in deoxyhemoglobin. Copyright © 2012 John Wiley & Sons, Ltd.     

Erythropoietin concentrations during 10 days of normobaric hypoxia under controlled environmental circumstances

Serum erythropoietin levels (s‐[epo]), haemoglobin concentration ([Hb]), haematocrit (hct), and ferritin concentration ([fer]) were measured in seven healthy male volunteers (20–23 years) exposed continuously to hypoxia (PO₂ 14 kPa) for 10 days. Serum erythropoietin concentration increased significantly from 9.5 ± 3.51 to 33.6 ± 11.64 U L^–1 (P < 0.05) after 2 days of hypoxia. Thereafter, s‐[epo] decreased. However, after 10 days s‐[epo] was 18.7 ± 5.83 U L^–1 which was still increased above the pre‐hypoxia level (P < 0.05). Serum haemoglobin concentration and hct increased over the 10 days of hypoxia, [Hb] from 152 ± 8.9 to 168 ± 9.2 gL^–1 (P < 0.001), and hct from 43 ± 2.4 to 49 ± 2.6% (P < 0.001). Ferritin concentration decreased significantly during the hypoxic exposure from 82 ± 46.9 to 44 ± 31.7 mmol L^–1 after 10 days (P < 0.01). In conclusion, the initial increase of s‐[epo] under controlled normobaric hypoxia was marked, 353%, and levelled off after 5–10 days at 62–97% above normoxia level. There was also a significant increase in [Hb] and hct and a decrease in [fer] after 10 days of exposure to normobaric hypoxia.     

The cortical and medullary blood flow at different levels of renal nerve activity

The effect of (1) renal denervation and (2) stimulation of the renal nerve on the regional renal blood flow were determined by the Rb uptake method. Under control conditions the total renal blood flow was 3.64±0.09 ml·min^-1·g^-1 tissue increasing significantly (p<0.02) to 4.39±0.28 ml·min^-1·g^-1 after denervation. Upon stimulation of the peripheral portions of the sectioned renal nerves the blood flow decreased almost linearly with the frequency of stimulation reaching 0.99±0.24 ml·min^-1·g^-1 at 10 Hz. Utilizing the relation between blood flow and stimulation frequency the control blood flow correspond to a spontaneous activity of 1.5 Hz. As expected the cortical blood flow responded in the same way as for the total renal blood flow. In the renal medulla denervation gave a much more pronounced response where e.g. the inner medullary flow increased from 0.88±0.09 to 1.30±0.16 ml·min^-1·g^-1, i.e. a 50% increase (p<0.05). Stimulation with 2 Hz produced a steep fall in the blood flow, whereafter it decreased linearly with the stimulation frequency reaching 0.11 ml·min^-1·g^-1 at 10 Hz stimulation. This demonstrates again that the renal medulla is sensitive to renal nerve activity primarily in the low level range. It should be remarked, however, that the 86-Rb uptake method reflects the effective blood flow, which might differ from the blood flow in absolute terms. It is concluded that the renal nerve activity influences the blood flow of all regions of the kidney within the entire range 0–10 Hz. The renal medullary blood flow is affected presumably to a greater extent in the low level range around the basal tone. The sympathetic nerves might then also be important with respect to the urine concentration mechanism.     

Phosphate excretion during 24 h of hypoxia in conscious rats

The objective of this study was to investigate renal phosphate excretion during 24 h of hypoxia in conscious rats fed by total parenteral nutrition. Wistar rats weighing 190 g were exposed to hypoxia (inspired oxygen fraction = 0.10) or normoxia (inspired oxygen fraction = 0.21) for 24 h in a normobaric chamber. Renal clearance and hormonal studies were performed. The results showed a greater fractional excretion of phosphate (5.37 pL 0.07%, P < 0.05) and hypophosphataemia (7.40 pL 0.12 mg dL^-1, P < 0.01) in hypoxic rats (n = 10) than in normoxic rats (n = 13; 3.50 pL 0.37% and 8.02 pL 0.16 mg dL^-1, respectively). In addition, during hypoxia there was a significant decrease in the excretion of urinary adenosine 3′,5′-cyclic monophosphate per glomerular filtrate (2.97 pL 1.27 nmol dL^-1, P < 0.005), a parameter of the renal action of parathyroid hormone, and a stable level of serum parathyroid hormone (10.2 pL 2.6 ng mL^-1) (cf. normoxia: 8.57 pL 0.70 nmol dL^-1 and 8.0 pL 1.7 ng mL^-1, respectively). However, creatinine clearance and the renal adenosine triphosphate level, both of which affect adenosine 3′,5′-cyclic monophosphate excretion, were not different between the two groups. These data suggest that exposure of conscious rats to 24 h of hypoxia causes renal hyporesponsiveness to physiological levels of parathyroid hormone, which is manifested as a decrease in adenosine 3′,5′-cyclic monophosphate excretion. Phosphaturia is not a direct net effect of hypoxia and secondary hypocapnia on renal phosphate transport, which is known to be regulated by parathyroid hormone through adenosine 3′,5′-cyclic monophosphate.