Brabrand Knut, de Lange Charlotte, Emblem Kyrre E, Reinholt Finn P, Saugstad Ola Didrik, Stokke Eirik Schram, Munkeby Berit H
From the *Department of Radiology and Nuclear Medicine, †The Intervention Centre, ‡Department of Pathology, §Department of Pediatric Research, and ∥Department of Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Invest Radiol. 2014 Aug;49(8):540-6. doi: 10.1097/RLI.0000000000000053.
It is well known from both clinical experience and animal research that renal hypoxia may lead to temporary or permanent renal failure, the severity being dependent largely on the duration and grade of the hypoxia. The medulla is more susceptible to hypoxic injury than the cortex because approximately 90% of the renal blood flow supplies the cortex. Various methods have been applied to evaluate renal perfusion in both experimental and clinical settings, including magnetic resonance imaging, computed tomography, laser Doppler, and contrast-enhanced ultrasound (CEUS).
The aim of this study was to evaluate changes in overall and regional renal perfusion with CEUS in response to global hypoxia.
Twelve newborn anesthetized piglets were exposed to general hypoxia with a fraction of inspired oxygen of 8% of 30 minutes duration. Resuscitation was performed with either 100% oxygen (n = 6) or air (21% oxygen) (n = 6) for 30 minutes followed by 7 hours of reoxygenation with air. Before, during, and after hypoxia, the left kidney was examined with CEUS using 0.2 mL IV of SonoVue followed by 2 mL saline flush. Five additional piglets served as controls. The kidney was examined using a 9-MHz linear transducer with low mechanical index (0.21) and pulse inversion contrast program. One region of interest was drawn in the renal cortex and 1 in the medulla to obtain the corresponding time intensity curves (TICs). From these curves, the peak intensity (PI), time to peak (TTP), upslope of the curve, area under the curve, and mean transit time (MTT) were recorded. Also, the renal arteriovenous transit time (AVTT) was registered. The resistance index (RI) was repeatedly measured in the renal artery. Contrast-enhanced ultrasound was repeated at regular intervals until the animals were sacrificed 8 hours after the hypoxic period.
In the group of 12 piglets subjected to hypoxia, RI increased from 0.69 ± 0.08 at baseline to 0.99 ± 0.09 during hypoxia (P < 0.01), indicating severe general renal vasoconstriction. The AVTT increased from 2.6 ± 0.5 seconds at baseline to 6.7 ± 2.8 seconds during hypoxia (P < 0.001). The PI in the cortex decreased from a mean value of 38.6 ± 6.1 dB at baseline to 30.3 ± 9.7 dB during hypoxia (P < 0.05). In the medulla, only a minor, nonsignificant reduction in PI was observed during hypoxia. In the medulla, TTP and MTT increased from 6.4 ± 1.5 and 9.2 ± 1.7 seconds at baseline to 14.6 ± 8.4 seconds (P < 0.01) and 15.2 ± 5.6 seconds (P < 0.01), respectively, during hypoxia. In the cortex, no statistically significant changes in TTP or MTT were observed during hypoxia. A return to near-baseline values was observed for TTP, PI in both the medulla and cortex, as well as for RI and AVTT within 1 to 3 hours after hypoxia, and they remained relatively constant for the duration of the experiment.Less than 1 hour after the hypoxia, PI both in the cortex and the medulla was significantly higher in the group resuscitated with air than in the group resuscitated with 100% oxygen, 36.0 ± 4.3 versus 27.2 ± 2.2 dB (P < 0.05) and 33.3 ± 8.2 versus 21.1 ± 2.0 dB (P < 0.01), respectively.
Global hypoxia induced changes in overall and regional renal perfusion detectable with CEUS. Cortical and medullary flows were affected differently by hypoxia; a strong increase in medullary TTP and MTT was observed, indicating a reduction in medullary blood flow velocity. In the cortex, a significant reduction in PI was found, probably because of a reduction in cortical blood volume. A faster recovery of both medullary and cortical PI in the group resuscitated with air could indicate that air might be more beneficial for renal perfusion than hyperoxia during resuscitation after renal hypoxia.
临床经验和动物研究均表明，肾脏缺氧可能导致暂时性或永久性肾衰竭，其严重程度很大程度上取决于缺氧的持续时间和程度。由于约90%的肾血流供应皮质，髓质比皮质更容易受到缺氧损伤。在实验和临床环境中，已经应用了多种方法来评估肾脏灌注，包括磁共振成像、计算机断层扫描、激光多普勒和对比增强超声（CEUS）。
本研究的目的是评估CEUS在整体和局部肾脏灌注方面对全身性缺氧的反应变化。
12只新生麻醉仔猪暴露于吸入氧分数为8%的全身性缺氧环境中30分钟。分别用100%氧气（n = 6）或空气（21%氧气）（n = 6）进行30分钟的复苏，然后用空气进行7小时的复氧。在缺氧前、缺氧期间和缺氧后，使用0.2 mL静脉注射声诺维，随后用2 mL生理盐水冲洗，对左肾进行CEUS检查。另外5只仔猪作为对照。使用9 MHz线性换能器，采用低机械指数（0.21）和脉冲反转造影程序对肾脏进行检查。在肾皮质绘制1个感兴趣区域，在髓质绘制1个感兴趣区域，以获得相应的时间强度曲线（TIC）。从这些曲线中，记录峰值强度（PI）、达峰时间（TTP）、曲线上升斜率、曲线下面积和平均通过时间（MTT）。此外，记录肾动静脉通过时间（AVTT）。在肾动脉中反复测量阻力指数（RI）。定期重复进行对比增强超声检查，直到在缺氧期后8小时处死动物。
在12只遭受缺氧的仔猪组中，RI从基线时的0.69±0.08增加到缺氧期间的0.99±0.09（P < 0.01），表明严重的全身性肾血管收缩。AVTT从基线时的2.6±约0.5秒增加到缺氧期间的6.7±2.8秒（P < 0.001）。皮质中的PI从基线时的平均值38.6±6.1 dB降低到缺氧期间的30.3±9.7 dB（P < 0.05）。在髓质中，缺氧期间仅观察到PI有轻微的、无统计学意义的降低。在髓质中，TTP和MTT从基线时的6.4±1.5秒和9.2±1.7秒分别增加到缺氧期间的14.6±8.4秒（P < 0.01）和15.2±5.6秒（P < 0.01）。在皮质中，缺氧期间未观察到TTP或MTT有统计学意义的变化。在缺氧后1至3小时内，观察到TTP、髓质和皮质中的PI以及RI和AVTT恢复到接近基线值，并且在实验期间它们保持相对稳定。缺氧后不到1小时，用空气复苏的组中皮质和髓质中的PI均显著高于用100%氧气复苏的组，分别为36.0±4.3 dB对27.2±2.2 dB（P < 0.05）和33.3±8.2 dB对21.1±2.0 dB（P < 0.01）。
全身性缺氧引起了CEUS可检测到的整体和局部肾脏灌注变化。皮质和髓质血流受缺氧的影响不同；观察到髓质TTP和MTT显著增加，表明髓质血流速度降低。在皮质中，发现PI显著降低，可能是由于皮质血容量减少。用空气复苏的组中髓质和皮质PI恢复更快，这可能表明在肾脏缺氧后的复苏过程中，空气对肾脏灌注可能比高氧更有益。
