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缺血后再灌注期间,低强度超声联合微泡治疗后毛细血管灌注增加。

Increase in capillary perfusion following low-intensity ultrasound and microbubbles during postischemic reperfusion.

作者信息

Bertuglia Silvia

机构信息

CNR Institute of Clinical Physiology, Faculty of Medicine, University of Pisa, Pisa, Italy.

出版信息

Crit Care Med. 2005 Sep;33(9):2061-7. doi: 10.1097/01.ccm.0000178356.90173.73.

DOI:10.1097/01.ccm.0000178356.90173.73
PMID:16148481
Abstract

OBJECTIVES

We postulated that the increase in shear stress caused by microbubbles in the presence of low-intensity ultrasound increases vasodilation in ischemia/reperfusion.

DESIGN

Prospective, randomized, and blinded experimental study.

SETTING

Research laboratory.

SUBJECTS

Forty hamsters were subjected to ischemia/reperfusion and observed by intravital microscopy.

INTERVENTIONS

Ultrasound (2.5 MHz, 1.3 mechanical index, 2.0 peak pressure) was applied to the hamster cheek pouch in ischemia/reperfusion with and without microbubbles (Levovist or Sono Vue) at baseline (15 mins) and at the beginning (15 mins) of reperfusion after ischemia (30 mins).

MEASUREMENTS AND MAIN RESULTS

Arterial diameter (A2-A3, 38.5 +/- 5.3 microm; A4,15.0 +/- 7.0 microm), red blood cell velocity, wall shear stress, permeability, perfused capillary length, and adherent leukocytes in venules were evaluated. Lipid peroxides were also determined in the systemic blood. Ultrasound and microbubbles in reperfusion significantly increased the diameter (A2-A3 Sono Vue, 33%; Levovist, 53% vs. ischemia/reperfusion, p < .05; A4, Sono Vue, 93%; Levovist, 104% vs. ischemia/reperfusion, p < .05), red blood cell velocity, flow, and shear stress in both A4 and A2-A3 arterioles. Shear stress was significantly higher with Levovist (A2-A3, 105%; A4, 185%) and Sono Vue (A2, 108%; A4, 140% vs. ischemia/reperfusion, p < .05) than ultrasound alone in arterioles. With ischemia/reperfusion, perfused capillary length was reduced significantly, whereas it increased with Levovist and Sono Vue (43%, 41% vs. ischemia/reperfusion p < .05). Lipid peroxides increased early during reperfusion and remained at increased levels throughout reperfusion. Lipid peroxides were unchanged after ultrasound alone or ultrasound with Sono Vue or Levovist during ischemia/reperfusion. With ultrasound there was a significant increase in vascular permeability vs. ischemia/reperfusion. Treatment with Sono Vue (-36%) and Levovist (-57%) decreased permeability vs. ischemia/reperfusion in reperfusion (p < .001). Ischemia/reperfusion had significantly increased leukocyte adhesion. Ultrasound alone (-39%) or with Sono Vue (-64%) and Levovist (-57%) caused smaller increases in leukocyte adhesion than ischemia/reperfusion (p < .05).

CONCLUSIONS

Ultrasound and microbubbles equilibrate microvascular shear stress, thus avoiding the failure of capillary perfusion in postischemic reperfusion.

摘要

目的

我们推测,在低强度超声存在的情况下,微泡引起的剪切应力增加会增强缺血/再灌注时的血管舒张。

设计

前瞻性、随机、双盲实验研究。

地点

研究实验室。

对象

40只仓鼠接受缺血/再灌注,并通过活体显微镜观察。

干预措施

在基线(15分钟)以及缺血(30分钟)后再灌注开始时(15分钟),对仓鼠颊囊施加超声(2.5兆赫,1.3机械指数,2.0峰值压力),分别在有和无微泡(声诺维或利声显)的情况下进行缺血/再灌注。

测量指标及主要结果

评估动脉直径(A2 - A3,38.5±5.3微米;A4,15.0±7.0微米)、红细胞速度、壁剪切应力、通透性、灌注毛细血管长度以及小静脉中黏附的白细胞。还测定了全身血液中的脂质过氧化物。再灌注时超声联合微泡显著增加了直径(A2 - A3,声诺维组增加33%;利声显组增加53%,与缺血/再灌注相比,p < 0.05;A4,声诺维组增加93%;利声显组增加104%,与缺血/再灌注相比,p < 0.05)、红细胞速度、血流量以及A4和A2 - A3小动脉中的剪切应力。在小动脉中,利声显(A2 - A3,增加105%;A4,增加185%)和声诺维(A2,增加108%;A4,增加140%,与缺血/再灌注相比,p < 0.05)引起的剪切应力显著高于单独超声。缺血/再灌注时,灌注毛细血管长度显著缩短,而利声显和声诺维使其增加(分别增加43%、41%,与缺血/再灌注相比,p < 0.05)。脂质过氧化物在再灌注早期增加,并在整个再灌注过程中维持在较高水平。在缺血/再灌注期间,单独超声或超声联合声诺维或利声显后脂质过氧化物无变化。与缺血/再灌注相比,超声使血管通透性显著增加。再灌注时,声诺维(降低36%)和利声显(降低57%)治疗使通透性低于缺血/再灌注(p < 0.001)。缺血/再灌注显著增加了白细胞黏附。单独超声(降低39%)或联合声诺维(降低64%)和利声显(降低57%)引起的白细胞黏附增加幅度小于缺血/再灌注(p < 0.05)。

结论

超声和微泡可平衡微血管剪切应力,从而避免缺血后再灌注时毛细血管灌注失败。

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