Evolution of cardiac and renal impairment detected by high-field cardiovascular magnetic resonance in mice with renal artery stenosis

Journal of Cardiovascular Magnetic Resonance

Lilach O Lerman³  Joseph P Grande²  Slobodan I Macura¹  Bruce E Knudsen²  John A Crane³  Behzad Ebrahimi³ 

[1] Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA;Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA;Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA

关键词: Hypoxia;    ASL;    BOLD;    Ultra-high field MRI;    LV dysfunction;    Renal artery stenosis;   

Others  :  803609
DOI  :  10.1186/1532-429X-15-98

 received in 2012-12-21, accepted in 2013-10-16,  发布年份 2013

【 摘 要 】

Background

Renal artery stenosis (RAS) promotes hypertension and cardiac dysfunction. The 2-kidney, 1-clip mouse model in many ways resembles RAS in humans and is amenable for genetic manipulation, but difficult to evaluate noninvasively. We hypothesized that cardiovascular magnetic resonance (CMR) is capable of detecting progressive cardiac and renal dysfunction in mice with RAS and monitoring the progression of the disease longitudinally.

Methods

RAS was induced at baseline in eighteen mice by constricting the renal artery. Nine additional animals served as normal controls. CMR scans (16.4 T) were performed in all mice one week before and 2 and 4 weeks after baseline. Renal volumes and hemodynamics were assessed using 3D fast imaging with steady-state precession and arterial spin labelling, and cardiac function using CMR cine. Renal hypoxia was investigated using blood oxygen-level dependent (BOLD) MR.

Results

Two weeks after surgery, mean arterial pressure was elevated in RAS mice. The stenotic kidney (STK) showed atrophy, while the contra-lateral kidney (CLK) showed hypertrophy. Renal blood flow (RBF) and cortical oxygenation level declined in the STK but remained unchanged in CLK. Moreover, cardiac end-diastolic and stroke volumes decreased and myocardial mass increased. At 4 weeks, STK RBF remained declined and the STK cortex and medulla showed development of hypoxia. Additionally, BOLD detected a mild hypoxia in CLK cortex. Cardiac end-diastolic and stroke volumes remained reduced and left ventricular hypertrophy worsened. Left ventricular filling velocities (E/A) indicated progression of cardiac dysfunction towards restrictive filling.

Conclusions

CMR detected longitudinal progression of cardiac and renal dysfunction in 2K, 1C mice. These observations support the use of high-field CMR to obtain useful information regarding chronic cardiac and renal dysfunction in small animals.

【 授权许可】

   
2013 Ebrahimi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Al-Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS, Sarnak MJ. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am College Cardiol. 2001; 38:955-62.
• [2]Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351:1296-305.
• [3]Khan NA, Ma IW, Thompson C, Humphries K, Salem D, Adeera L. Decline in kidney function is associated with increased mortality among patients with left ventricular systolic dysfunction. J Gen Int Med. 2005; 20:84-5.
• [4]Lerman LO, Textor SC, Grande JP. Mechanisms of tissue injury in renal artery stenosis: ischemia and beyond. Prog Cardiovasc Dis. 2009; 52:196-203.
• [5]Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med. 2001; 344:431-42.
• [6]Takimoto E, Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension. 2007; 49:241-8.
• [7]Zoccali C, Mallamaci F, Tripepi G. Novel cardiovascular risk factors in end-stage renal disease. J Am Soc Nephrol. 2004; 15 Suppl 1:S77-80.
• [8]Capasso JM, Palackal T, Olivetti G, Anversa P. Left ventricular failure induced by long-term hypertension in rats. Circ Res. 1990; 66:1400-12.
• [9]Cheng J, Zhou W, Warner GM, Knudsen BE, Garovic VD, Gray CE, Lerman LO, Platt JL, Romero JC, Textor SC et al.. Temporal analysis of signaling pathways activated in a murine model of two-kidney, one-clip hypertension. Am J Physiol Renal Physiol. 2009; 297:F1055-68.
• [10]Sun Y, Carretero OA, Xu J, Rhaleb NE, Yang JJ, Pagano PJ, Yang XP. Deletion of inducible nitric oxide synthase provides cardioprotection in mice with 2-kidney, 1-clip hypertension. Hypertension. 2009; 53:49-56.
• [11]Arruda RM, Peotta VA, Meyrelles SS, Vasquez EC. Evaluation of vascular function in apolipoprotein E knockout mice with angiotensin-dependent renovascular hypertension. Hypertension. 2005; 46:932-6.
• [12]Cervenka L, Vaneckova I, Huskova Z, Vanourkova Z, Erbanova M, Thumova M, Skaroupkova P, Opocensky M, Maly J, Chabova VC et al.. Pivotal role of angiotensin II receptor subtype 1A in the development of two-kidney, one-clip hypertension: study in angiotensin II receptor subtype 1A knockout mice. J Hyper. 2008; 26:1379-89.
• [13]Wiesel P, Patel AP, Carvajal IM, Wang ZY, Pellacani A, Maemura K, DiFonzo N, Rennke HG, Layne MD, Yet SF et al.. Exacerbation of chronic renovascular hypertension and acute renal failure in heme oxygenase-1-deficient mice. Circ Res. 2001; 88:1088-94.
• [14]Slovut DP, Olin JW. Current concepts - Fibromuscular dysplasia. New Engl J Med. 2004; 350:1862-71.
• [15]Greene ER, Venters MD, Avasthi PS, Conn RL, Jahnke RW. Noninvasive characterization of renal artery blood flow. Kidney Int. 1981; 20:523-9.
• [16]Wei K, Le E, Bin JP, Coggins M, Thorpe J, Kaul S. Quantification of renal blood flow with contrast-enhanced ultrasound. J Am Coll Cardiol. 2001; 37:1135-40.
• [17]Coulam CH, Bouley DM, Sommer FG. Measurement of renal volumes with contrast-enhanced MRI. J Magn Reson Imaging. 2002; 15:174-9.
• [18]Karger N, Biederer J, Lusse S, Grimm J, Steffens JC, Heller M, Gluer CC. Quantitation of renal perfusion using arterial spin labeling with FAIR-UFLARE. Magn Reson Imaging. 2000; 18:641-7.
• [19]Vallee JP, Lazeyras F, Khan HG, Terrier F. Absolute renal blood flow quantification by dynamic MRI and Gd-DTPA. Eur Radiol. 2000; 10:1245-52.
• [20]Juillard L, Lerman LO, Kruger DG, Haas JA, Rucker BC, Polzin JA, Riederer SJ, Romero JC. Blood oxygen level-dependent measurement of acute intra-renal ischemia. Kidney Int. 2004; 65:944-50.
• [21]Prasad PV, Edelman RR, Epstein FH. Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. Circulation. 1996; 94:3271-5.
• [22]Palm F, Nordquist L. Renal oxidative stress, oxygenation, and hypertension. Am J Physiol Regul Integr Comp Physiol. 2011; 301:R1229-41.
• [23]Quinones MA, Waggoner AD, Reduto LA, Nelson JG, Young JB, Winters WL, Ribeiro LG, Miller RR. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography. Circulation. 1981; 64:744-53.
• [24]Bloomgarden DC, Fayad ZA, Ferrari VA, Chin B, Sutton MGSJ, Axel L. Global cardiac function using fast breath-hold MRI: Validation of new acquisition and analysis techniques. Magnet Reson Med. 1997; 37:683-92.
• [25]Vallee JP, Ivancevic MK, Nguyen D, Morel DR, Jaconi M. Current status of cardiac MRI in small animals. MAGMA. 2004; 17:149-56.
• [26]Schneider JE, Lanz T, Barnes H, Medway D, Stork LA, Lygate CA, Smart S, Griswold MA, Neubauer S. Ultra-fast and accurate assessment of cardiac function in rats using accelerated MRI at 9.4 Tesla. Magnet Reson Med. 2008; 59:636-41.
• [27]Warner GM, Cheng J, Knudsen BE, Gray CE, Deibel A, Juskewitch JE, Lerman LO, Textor SC, Nath KA, Grande JP. Genetic deficiency of Smad3 protects the kidneys from atrophy and interstitial fibrosis in 2K1C hypertension. Am J Physiol Renal Physiol. 2012; 302:F1455-64.
• [28]Di Leo G, Di Terlizzi F, Flor N, Morganti A, Sardanelli F. Measurement of renal volume using respiratory-gated MRI in subjects without known kidney disease: Intraobserver, interobserver, and interstudy reproducibility. Eur J Radiol. 2011; 80:E212-6.
• [29]Li LP, Ji L, Lindsay S, Prasad PV. Evaluation of intrarenal oxygenation in mice by BOLD MRI on a 3.0T human whole-body scanner. J Magn Reson Imaging. 2007; 25:635-8.
• [30]Yang QX, Williams GD, Demeure RJ, Mosher TJ, Smith MB. Removal of local field gradient artifacts in T-2*-weighted images at high fields by gradient-echo slice excitation profile imaging. Magnet Reson Med. 1998; 39:402-9.
• [31]Larson AC, White RD, Laub G, McVeigh ER, Li D, Simonetti OP. Self-gated cardiac cine MRI. Magn Reson Med. 2004; 51:93-102.
• [32]Zhou R, Pickup S, Glickson JD, Scott CH, Ferrari VA. Assessment of global and regional myocardial function in the mouse using Cine and tagged MRI. Magnet Reson Med. 2003; 49:760-4.
• [33]Stuckey DJ, Carr CA, Tyler DJ, Aasum E, Clarke K. Novel MRI method to detect altered left ventricular ejection and filling patterns in rodent models of disease. Magnet Reson Med. 2008; 60:582-7.
• [34]Murphy WR, Coleman TG, Smith TL, Stanek KA. Effects of graded renal artery constriction on blood pressure, renal artery pressure, and plasma renin activity in Goldblatt hypertension. Hypertension. 1984; 6:68-74.
• [35]Makino A, Skelton MM, Zou AP, Roman RJ, Cowley AW. Increased renal medullary oxidative stress produces hypertension. Hypertension. 2002; 39:667-72.
• [36]Sigmon DH, Beierwaltes WH. Influence of nitric oxide in the chronic phase of two-kidney, one clip renovascular hypertension. Hypertension. 1998; 31:649-56.
• [37]Cacciapuoti F. Molecular mechanisms of left ventricular hypertrophy (LVH) in systemic hypertension (SH)-possible therapeutic perspectives. J Am Soc Hypertens. 2011; 5:449-55.
• [38]Pennell DJ. Cardiovascular magnetic resonance: twenty-first century solutions in cardiology. Clin Med. 2003; 3:273-8.
• [39]Rountas C, Vlychou M, Vassiou K, Liakopoulos V, Kapsalaki E, Koukoulis G, Fezoulidis IV, Stefanidis I. Imaging modalities for renal artery stenosis in suspected renovascular hypertension: prospective intraindividual comparison of color Doppler US, CT angiography, GD-enhanced MR angiography, and digital substraction angiography. Ren Fail. 2007; 29:295-302.
• [40]Bunck AC, Engelen MA, Schnackenburg B, Furkert J, Bremer C, Heindel W, Stypmann J, Maintz D. Feasibility of functional cardiac MR imaging in mice using a clinical 3 Tesla whole body scanner. Invest Radiol. 2009; 44:749-56.
• [41]Daire JL, Jacob JP, Hyacinthe JN, Croisille P, Montet-Abou K, Richter S, Botsikas D, Lepetit-Coiffe M, Morel D, Vallee JP. Cine and tagged cardiovascular magnetic resonance imaging in normal rate at 1.5 T: a rest and stress study. J Cardiovasc Magn R. 2008; 10:48. BioMed Central Full Text
• [42]Stuckey DJ, Carr CA, Tyler DJ, Clarke K. Cine-MRI versus two-dimensional echocardiography to measure in vivo left ventricular function in rat heart. Nmr in Biomed. 2008; 21:765-72.
• [43]Gardener AG, Gowland PA, Francis ST. Implementation of quantitative perfusion imaging using pulsed arterial spins labeling at ultra-high field. Magnet Reson Med. 2009; 61:874-82.
• [44]Hecht EM, Lee RF, Taouli B, Sodickson DK. Perspectives on body MR imaging at ultrahigh field. Magn Reson Imaging Clin N Am. 2007; 15:449-65. viii
• [45]Prasad PV. Functional MRI of the kidney: tools for translational studies of pathophysiology of renal disease. Am J Physiol Renal Physiol. 2006; 290:F958-74.
• [46]Abduljalil AM, Robitaille PML. Macroscopic susceptibility in ultra high field MRI. J Comput Assist Tomo. 1999; 23:832-41.
• [47]Gloviczki ML, Glockner J, Gomez SI, Romero JC, Lerman LO, McKusick M, Textor SC. Comparison of 1.5 and 3 T BOLD MR to study oxygenation of kidney cortex and medulla in human renovascular disease. Invest Radiol. 2009; 44:566-71.
• [48]Rognant N, Guebre-Egziabher F, Bacchetta J, Janier M, Hiba B, Langlois JB, Gadet R, Laville M, Juillard L. Evolution of renal oxygen content measured by BOLD MRI downstream a chronic renal artery stenosis. Nephrol Dial Transplant. 2011; 26:1205-10.