No abstract

Objectives Magnetic Resonance Elastography (MRE) allows noninvasive assessment of tissue stiffness in vivo. Renal arterial stenosis (RAS), a narrowing of the renal artery, promotes irreversible tissue fibrosis that threatens kidney viability and may elevate tissue stiffness. However, kidney stiffness may also be affected by hemodynamic factors. This study tested the hypothesis that renal blood flow (RBF) is an important determinant of renal stiffness as measured by MRE. Material and Methods In six anesthetized pigs MRE studies were performed to determine cortical and medullary elasticity during acute graded decreases in RBF (by 20, 40, 60, 80, and 100% of baseline) achieved by a vascular occluder. Three sham-operated swine served as time control. Additional pigs were studied with MRE six weeks after induction of chronic unilateral RAS (n=6) or control (n=3). Kidney fibrosis was subsequently evaluated histologically by trichrome staining. Results During acute RAS the stenotic cortex stiffness decreased (from 7.4 ± 0.3 to 4.8 ± 0.6 kPa, p=0.02 vs. baseline) as RBF decreased. Furthermore, in pigs with chronic RAS (80±5.4% stenosis) in which RBF was decreased by 60±14% compared to controls, cortical stiffness was not significantly different from normal (7.4 ± 0.3 vs. 7.6 ± 0.3 kPa, p=0.3), despite histological evidence of renal tissue fibrosis. Conclusion Hemodynamic variables modulate kidney stiffness measured by MRE and may mask the presence of fibrosis. These results suggest that kidney turgor should be considered during interpretation of elasticity assessments.

Objective Transition from obesity to metabolic-syndrome (MetS) promotes cardiovascular diseases, but the underlying cardiac pathophysiological mechanisms are incompletely understood. We tested the hypothesis that development of insulin resistance (IR) and MetS is associated with impaired myocardial cellular turnover. Methods and results MetS-prone Ossabaw pigs were randomized to 10 weeks of standard chow (lean), or to 10 (obese) or 14 (MetS) weeks of atherogenic diet (n=6 each). Cardiac structure, function, and myocardial oxygenation were assessed by multidetector computed-tomography and Blood-Oxygen-Level-Dependent (BOLD)-magnetic resonance imaging (MRI), the microcirculation with micro-computed-tomography, and injury mechanisms by immunoblotting and histology. Both obese and MetS showed obesity and dyslipidemia, while only MetS showed IR. Cardiac output and myocardial perfusion increased only in MetS, yet BOLD-MRI showed hypoxia. Inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis also increased in both obese and MetS, but more pronouncedly in MetS. Furthermore, autophagy in MetS was decreased and accompanied by marked apoptosis. Conclusions Development of IR characterizing a transition from obesity to MetS is associated with progressive changes of myocardial autophagy, apoptosis, inflammation, mitochondrial dysfunction, and fibrosis. Restoring myocardial cellular turnover may represent a novel therapeutic target for preserving myocardial structure and function in obesity and MetS.

Atherosclerotic renal artery stenosis has a range of manifestations depending upon the severity of vascular occlusion. The aim of this study was to examine whether exceeding the limits of adaptation to reduced blood flow ultimately leads to tissue hypoxia as determined by blood oxygen level dependent (BOLD) MR imaging. We compared three groups of hypertensive patients (24 with essential hypertension [EH]), 13 with “moderate” (Doppler velocities 200-384 cm/sec) and 17 with “severe” atherosclerotic renal artery stenosis ([ARAS]; velocities above 384 cm/sec and loss of functional renal tissue). Cortical and medullary blood flows and volumes were determined by multi-detector CT. Post-stenotic kidney size and blood flow were reduced with ARAS, and tissue perfusion fell in the most severe lesions. Tissue deoxyhemoglobin, as reflected by R2* values, was higher in medulla as compared to cortex for all groups and did not differ between subjects with renal artery lesions and EH. By contrast, cortical R2* levels were elevated for severe ARAS (21.6 ±9.4 /sec) as compared with either EH (17.8±2.3 /sec, p<.01) or moderate ARAS (15.7± 2.1 /sec, p<.01). Changes in medullary R2* after furosemide administration tended to be blunted in severe ARAS as compared to unaffected (contralateral) kidneys. These results demonstrate that severe vascular occlusion overwhelms the capacity of the kidney to adapt to reduced blood flow, manifest as overt cortical hypoxia as measured by BOLD MRI. The level of cortical hypoxia is out of proportion to medulla and may provide a marker to identify irreversible parenchymal injury.