Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes.

The objective of this study was to compare the ratio of renal oxygen availability (RO2) to glomerular filtration rate (GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO2 was estimated by blood oxygen level-dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and p-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and M/I was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%). The RO2:GFR (ms/mL/min) was calculated as RO2 (T2*, ms) divided by GFR (mL/min). Whole-kidney RO2:GFR was 25% lower in adolescents with T1D versus control patients (P < 0.0001). In adolescents with T1D, lower whole-kidney RO2:GFR was associated with higher UACR (r = -0.31, P = 0.03), RPF (r = -0.52, P = 0.0009), and fat mass (r = -0.33, P = 0.02). Lower medullary RO2:GFR was associated with lower M/I (r = 0.31, P = 0.03). In conclusion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.

Use of electrical stimulation to monitor lumbosacral epidural and intrathecal needle placement in rabbits.

OBJECTIVE: To determine the minimal electric threshold of neurostimulation dorsally and ventrally to the interarcuate ligament in the lumbosacral area necessary to cause muscle contraction of the hind limb or tail and determine whether a continuous electrical stimulation applied to an insulated needle during lumbosacral epidural needle placement could be used to distinguish the epidural from the intrathecal space in rabbits. ANIMALS: 24 New Zealand white rabbits. PROCEDURES: Rabbits received iohexol (0.2 mL/kg) either dorsally (group 1) or ventrally to the interarcuate ligament in the lumbosacral area (groups 2 and 3). Correct placement of the needle was determined by use of the loss of resistance to injection technique (group 2) or a continuous electrical stimulation (group 3) and confirmed by examination of the iohexol distribution pattern on radiographs. RESULTS: In all rabbits of group 1, iohexol was injected in the lumbosacral area, outside the epidural space. In groups 2 and 3, iohexol was injected intrathecally. No pure iohexol epidural migration of iohexol was observed. Mean ± SD minimal electric threshold to elicit a motor response was 1.2 ± 0.3 mA, 0.3 ± 0.1 mA, and 0.3 ± 0.1 mA in groups 1, 2, and 3, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Neurostimulation was a useful technique to determine correct intrathecal needle placement in rabbits but failed to detect the lumbosacral epidural space when the common technique, used in dogs and cats for the lumbosacral epidural approach, was used.

Evaluation of the effects of noniodinized and iodinized ionic contrast media and gadoteric acid in acute necrotizing pancreatitis: experimental study in rabbits.

OBJECTIVE: To evaluate the effects of iodine contrast media and gadoteric acid in acute necrotizing pancreatitis. METHODS: Fifty rabbits were distributed in 5 groups: 10 rabbits were assigned in the control group (group 5) and 40 rabbits were assigned in the pancreatitis group, wherein acute necrotizing pancreatitis was induced through retrograde injection of 5% sodium taurocholate (1 mL/kg weight) in the main pancreatic duct. After 3 hours, they were randomized to receive endovenous iodinized nonionic contrast medium (group 1), iodinized ionic contrast medium (group 2), gadoteric acid (group 3), and physiological serum at 0.9% (group 4). Six hours after induction of pancreatitis, these animals were reoperated. During surgery, pancreatic tissue flow through laser Doppler, hematometric values, biochemistry, and histopathology analysis by hematoxylin and eosin were done. Statistical analysis using Kruskal-Wallis, Fisher-Freeman-Halton, and parametric t tests was performed. RESULTS: There was statistical significance when comparing tissue flow before and after induction of pancreatitis (P < 0.0001). Ionic and nonionic contrast media and gadoteric acid did not increase the grade of pancreatic necrosis (P > 0.05). CONCLUSIONS: Ionic and nonionic contrast media and gadoteric acid did not produce adverse effects in the present model of acute necrotizing pancreatitis.

Evaluation of the nitric oxide production in rat renal artery smooth muscle cells culture exposed to radiocontrast agents.

BACKGROUND: Radiocontrast agents (RC), substances largely used in diagnostic procedures, present the nephrotoxicity as one of its major side effects, which could be due to an altered synthesis of vasodilators. The aim of the present study was to evaluate the nitric oxide (NO) production in rat renal artery smooth muscle cells primary culture (rVSMC) exposed to RC. METHODS: The cells were treated for 72 hours with mannitol at 10% (MT10; 600 mOsm/kg H2O) or 35% (MT35; 2100 mOsm/kg H2O), with the nonionic iobitridol (IBT), the low-osmolality ioxaglate (IXG), the high-osmolality ioxitalamate (IXT), the nonionic, iso-osmolar iodixanol (IDX), and with lipopolysaccharide (LPS). We determined the NO and osmolality in the cell culture media and the cellular viability. RESULTS: By the Griess and chemiluminescence methods, the NO was not different in MT10 and IDX, but decreased in MT35, IBT, IXG, and IXT when compared with the control; it was increased in LPS and also decreased in all RC+LPS when compared with LPS. MT35, IXT, and IXT+LPS decreased the cellular viability, and the media osmolality was increased in MT35 and IXT compared with the control. CONCLUSION: The RC (except IDX) significantly reduced NO in rVSMC, which was more pronounced after IXT treatment (57.3%). This was not related to the reduced cell viability (15.8%) or to its high osmolality, because in MT35, with similar osmolality as IXT, NO decreased only 11.0% relatively to the control. Neither the media osmolality nor the cell viability was altered by IXG or IBT. The decreased NO could explain the vasoconstriction and, therefore, the acute renal failure by RC.