RESUMEN
Oxygen consumption beyond the proximal tubule is mainly determined by active solute reabsorption, especially in the thick ascending limb of the Loop of Henle. Furosemide-induced suppression of oxygen consumption (FSOC) involves inhibition of sodium transport in this segment, which is normally accompanied by a marked decrease in the intrarenal deoxyhemoglobin detectable by blood oxygen level-dependent (BOLD)-magnetic resonance imaging (MRI). This study tested the hypothesis that the magnitude of BOLD-MRI signal change after furosemide is related to impaired renal function in renovascular hypertension. In 16 pigs with unilateral renal artery stenosis, renal hemodynamics, function, and tubular function (FSOC and fluid concentration capacity) were evaluated in both kidneys using MR and multidetector computerized tomography (MDCT) imaging. Animals with adequate FSOC (23.6 +/- 2.2%, P > 0.05 vs. baseline) exhibited a mean arterial pressure (MAP) of 113 +/- 7 mmHg, and relatively preserved glomerular filtration rate (GFR) of 60 +/- 4.5 ml/min, comparable to their contralateral kidney (66 +/- 4 ml/min, P > 0.05). In contrast, animals with low FSOC (3.1 +/- 2.1%, P = NS vs. baseline) had MAP of 124 +/- 9 mmHg and GFR (22 +/- 6 ml/min) significantly lower than the contralateral kidneys (66 +/- 4 ml/min, P < 0.05). The group with preserved GFR and FSOC showed an increase in intratubular fluid concentration as assessed by MDCT that was greater than that observed in the low GFR group, suggesting better preservation of tubular function in the former group. These results suggest that changes in BOLD-MRI after furosemide can differentiate between underperfused kidneys with preserved tubular function and those with tubular dysfunction. This approach may allow more detailed physiologic evaluation of poststenotic kidneys in renovascular hypertension than previously possible.
Asunto(s)
Hipertensión Renovascular/fisiopatología , Hipoxia/fisiopatología , Médula Renal/fisiopatología , Consumo de Oxígeno , Animales , Diuréticos , Femenino , Furosemida , Tasa de Filtración Glomerular , Hipertensión Renovascular/metabolismo , Hipoxia/metabolismo , Médula Renal/metabolismo , Túbulos Renales/metabolismo , Túbulos Renales/fisiopatología , Imagen por Resonancia Magnética , Oxígeno/sangre , Circulación Renal , PorcinosRESUMEN
Ischemic nephropathy describes progressive renal failure, defined by significantly reduced glomerular filtration rate, and may be due to renal artery stenosis (RAS), a narrowing of the renal artery. It is unclear whether ischemia is present during RAS since a decrease in renal blood flow (RBF), O(2) delivery, and O(2) consumption occurs. The present study tests the hypothesis that despite proportional changes in whole kidney O(2) delivery and consumption, acute progressive RAS leads to decreases in regional renal tissue O(2). Unilateral acute RAS was induced in eight pigs with an extravascular cuff. RBF was measured with an ultrasound flow probe. Cortical and medullary tissue oxygen (P(t(O(2)))) of the stenotic kidney was measured continuously with sensors during baseline, three sequentially graded decreases in RBF, and recovery. O(2) consumption decreased proportionally to O(2) delivery during the graded stenosis (19 +/- 10.8, 48.2 +/- 9.1, 58.9 +/- 4.7 vs. 15.1 +/- 5, 35.4 +/- 3.5, 57 +/- 2.3%, respectively) while arterial venous O(2) differences were unchanged. Acute RAS produced a sharp reduction in O(2) efficiency for sodium reabsorption (P < 0.01). Cortical (P(t(O(2)))) decreases are exceeded by medullary decreases during stenosis (34.8 +/- 1.3%). Decreases in tissue oxygenation, more pronounced in the medulla than the cortex, occur despite proportional reductions in O(2) delivery and consumption. This demonstrates for the first time that hypoxia is present in the early stages of RAS and suggests a role for hypoxia in the pathophysiology of this disease. Furthermore, the notion that arteriovenous shunting and increased stoichiometric energy requirements are potential contributors toward ensuing hypoxia with graded and progressive acute RAS cannot be excluded.
Asunto(s)
Hipoxia/etiología , Isquemia/etiología , Corteza Renal/irrigación sanguínea , Médula Renal/irrigación sanguínea , Consumo de Oxígeno , Oxígeno/metabolismo , Obstrucción de la Arteria Renal/fisiopatología , Circulación Renal , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Metabolismo Energético , Tasa de Filtración Glomerular , Hipoxia/metabolismo , Hipoxia/fisiopatología , Electrodos de Iones Selectos , Isquemia/metabolismo , Isquemia/fisiopatología , Corteza Renal/metabolismo , Médula Renal/metabolismo , Oxígeno/sangre , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/metabolismo , Sodio/metabolismo , Sus scrofaRESUMEN
PURPOSE: To prospectively compare in pigs three mathematic models for assessment of glomerular filtration rate (GFR) on electron-beam (EB) computed tomographic (CT) images, with concurrent inulin clearance serving as the reference standard. MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. Inulin clearance was measured in nine pigs (18 kidneys) and compared with single-kidney GFR assessed from renal time-attenuation curves (TACs) obtained with EB CT before and after infusion of the vasodilator acetylcholine. CT-derived GFR was calculated with the original and modified Patlak methods and with previously validated extended gamma variate modeling of first-pass cortical TACs. Statistical analysis was performed to assess correlation between CT methods and inulin clearance for estimation of GFR with least-squares regression analysis and Bland-Altman graphical representation. Comparisons within groups were performed with a paired t test. RESULTS: GFR assessed with the original Patlak method indicated poor correlation with inulin clearance, whereas GFR assessed with the modified Patlak method (P < .001, r = 0.75) and with gamma variate modeling (P < .001, r = 0.79) correlated significantly with inulin clearance and indicated an increase in response to acetylcholine. CONCLUSION: CT-derived estimates of GFR can be significantly improved by modifications in image analysis methods (eg, use of a cortical region of interest).
Asunto(s)
Tasa de Filtración Glomerular/fisiología , Riñón/fisiología , Modelos Biológicos , Tomografía Computarizada por Rayos X/métodos , Acetilcolina/farmacología , Animales , Medios de Contraste , Procesamiento de Imagen Asistido por Computador/métodos , Inulina/farmacocinética , Yopamidol , Riñón/diagnóstico por imagen , Corteza Renal/diagnóstico por imagen , Corteza Renal/fisiología , Pruebas de Función Renal , Médula Renal/diagnóstico por imagen , Médula Renal/fisiología , Túbulos Renales/diagnóstico por imagen , Túbulos Renales/fisiología , Tasa de Depuración Metabólica , Técnica de Sustracción , Porcinos , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: Ischemic nephropathy is a common cause of end-stage renal disease. Exploration of the mechanisms of deterioration of renal function is limited due to lack of noninvasive techniques available to study the single kidney. The Blood Oxygen Level-Dependent (BOLD) MRI method can measure deoxyhemoglobin and therefore indirectly estimates renal oxygen content, but has never been evaluated in renal artery stenosis (RAS). This study was therefore designed to test if BOLD can detect the characteristic of renal hypoxia induced by RAS. METHODS: RAS was induced in 8 pigs using an occluder placed around the right renal artery. Renal blood flow (RBF) was measured continuously with an ultrasound probe. BOLD signal was measured bilaterally in the cortex and medulla (as the slope of the logarithm of MR signal) at baseline and at the lower limit of RBF autoregulation. The measurements were then repeated during six sequential graded decreases in RBF (80 to 0% of baseline) and during recovery. RESULTS: During the control period, BOLD signals were not significantly different between the right and the left kidneys. In the occluded kidney, BOLD signal of the cortex (19.3 +/- 1.9/s) and the medulla (17.3 +/- 2.0/s) increased during occlusion gradually and significantly (P < 0.0001) to a maximum (at total occlusion) of 33.8 +/- 2.0/s (+79%) and 29.8 +/- 2.3/s (+78%), respectively, and returned to baseline values during recovery. CONCLUSION: This study shows that the BOLD technique can noninvasively detect change in intra-renal oxygenation during an acute reduction of RBF. This study provides a strong rationale for developing the BOLD method for the detection and evaluation of renal hypoxia induced by RAS, which may be potentially applicable in humans.
Asunto(s)
Isquemia/sangre , Isquemia/diagnóstico , Imagen por Resonancia Magnética/métodos , Oxígeno/sangre , Obstrucción de la Arteria Renal/sangre , Obstrucción de la Arteria Renal/diagnóstico , Enfermedad Aguda , Animales , Tasa de Filtración Glomerular , Inulina/sangre , Inulina/orina , Isquemia/fisiopatología , Corteza Renal/irrigación sanguínea , Corteza Renal/fisiopatología , Médula Renal/irrigación sanguínea , Médula Renal/fisiopatología , Oxihemoglobinas/metabolismo , Obstrucción de la Arteria Renal/fisiopatología , Circulación Renal , Sus scrofaRESUMEN
We examined whether interactions between angiotensin II (Ang II), endothelin (ET), nitric oxide (NO), and prostaglandins (PGs) differentially regulate perfusion to distinct vascular beds. For this, we blocked either angiotensin AT1 or ET receptors or both and then sequentially inhibited NO and PG synthesis in anesthetized dogs. Blocking Ang II or ET had similar effects on systemic hemodynamics: Mean arterial pressure fell slightly without altering cardiac output. Blocking both caused a synergistic fall in mean arterial pressure and increased cardiac output. Pulmonary vascular resistance was not altered by blocking Ang II, ET, or both but progressively increased during NO and PG blockade in group 2 (which had unblocked ET receptors), suggesting that endogenous ET exerts pulmonary vasoconstriction that is tempered by NO and PGs. In the kidney, blocking Ang II increased regional blood flow (RBF), glomerular filtration rate (GFR), and fractional excretion of sodium (FENa). In contrast, blocking ET did not alter RBF, and it decreased GFR and FENa. Combined Ang II and ET blockade markedly increased RBF without altering GFR, and FENa was maintained at the levels as when only ET was blocked. Sequentially inhibiting NO and PGs decreased RBF when Ang II or ET were blocked but had little effect when both were blocked. Finally, Ang II or ET blockade did not alter iliac blood flow. Inhibiting NO and PGs decreased iliac blood flow when Ang II or ET but not both were blocked. These results suggest that regional differences in the interactions between endogenous Ang II, ET, NO, and PGs are important determinants in systemic, pulmonary, and regional hemodynamics.