Impact of hypertonic-hyperoncotic saline solutions on ischemia-reperfusion injury

描述（由申请人提供）：拟议研究的中心目的是评估调制成像作为一种方法的可行性，该方法将提供客观功能参数，可用于确定组织重建皮瓣在静脉和动脉闭塞条件下的状态，以及对高渗-高渗盐水溶液再灌注的反应。使用组织转移皮瓣是一种将组织从供体位置移动到受体位置并将动脉和静脉重新连接到受体位置的血管的方法。这一过程的医疗用途是允许创伤后重建手术，以及手术切除癌症后。然而，这种类型的手术容易失败，这可能是由于1)动脉或静脉机械阻塞引起的血管功能不全；2)游离组织瓣时因血流不足对移植组织造成损伤；3)由于缺血再灌注（I/R）损伤，这是在血流返回转移组织后造成的。游离组织移植术后第一天的特点是存在微血管并发症和移植组织坏死损失的风险。组织移植皮瓣的丢失对外科医生和患者来说都是一个毁灭性的经历。减少皮瓣损失的策略包括开发检测皮瓣受损的新技术和使用减少缺血再灌注损伤的液体。早在显微外科时代，皮瓣监测是基于临床观察皮肤颜色、毛细血管充盈和真皮出血。事实上，这仍然是护理的标准。然而，与人员配置相关的问题以及与临床确定皮瓣灌注相关的主观变化导致了对评估皮瓣状态的客观方法的探索。调制成像（MI）是测量体内组织氧合的一种很有前途的技术。MI是一种基于漫射光谱学原理的非接触成像方法，采用图案照明。MI可以在宽视场范围内快速定量确定光学特性。当与多光谱成像相结合时，MI可以量化与皮瓣健康相关的体内发色团浓度，即氧和脱氧血红蛋白和水浓度。我们介绍了一项初步的体内心肌梗死研究的结果，该研究使用了啮齿动物背部皮肤蒂皮瓣模型。这使我们能够评估心肌梗死推断组织血红蛋白、氧合和水合的空间分辨图的可行性。在这里，我们建议心肌梗死可用于定量评估皮瓣在高渗-高渗盐水溶液的辅助下对血管闭塞和再灌注的反应。拟议研究的结果将为组织转移皮瓣领域涉及MI的进一步调查提供信息，最终目标是在临床领域开发和部署该技术。公共卫生相关性：使用组织转移皮瓣是一种将组织从供体位置移动到受体位置并将动脉和静脉重新连接到受体位置的血管的方法。然而，这种类型的重建手术容易失败，这可能包括由于缺血再灌注损伤和血管功能不全引起的并发症。我们建议测试一种新的成像设备，它将有能力指导重建手术和术后恢复，既减少术后发病率，又减少皮瓣愈合的不确定性。最终，如果这项技术被证明是有效的，除了改善手术效果外，还可能减少住院时间和伴随的医疗保健费用。

DESCRIPTION (provided by applicant): The central aim of the proposed research is to assess the viability of Modulated Imaging as a method that will provide objective functional parameters that can be used to determine status of tissue reconstruction flaps under conditions of venous and arterial occlusion and in response to reperfusion using hypertonic -hyperoncotic saline solutions. The use of tissue transfer flaps is a method of moving tissue from a donor location to recipient location and re-attaching the arteries & veins to the blood vessels at the recipient site. The medical utility of this process is to allow for reconstructive surgery after trauma, as well as after surgical resection of cancer. This type of surgery is subject to failure however, which may be due to1) vascular insufficiency caused by to mechanical obstruction of the artery or vein; 2) injury caused to the transferred tissues due to the lack of blood flow when a free tissue flap is performed; or 3) due to ischemia-reperfusion (I/R) injury, which results after blood flow has been returned to the transferred tissue. The first postoperative days after free tissue transfer are characterized by the risk of microvascular complications and loss of transferred tissue by necrosis. Loss of a tissue transfer flap is a devastating experience to both the surgeon and the patient. Strategies for reducing flap loss involve both development of new technologies that detect flap compromise and the use of fluids that minimize ischemia-reperfusion injury. Early in the era of microsurgery, flap monitoring was performed based on clinical observation of skin color, capillary refill, and dermal bleeding. In fact, this remains the standard of care. However, issues related to staffing and subjective variations related to making a clinical determination of a flap's perfusion have led to the search for objective methods of assessment of flap status. One promising technology for measuring tissue oxygenation in-vivo is Modulated Imaging (MI). MI is a noncontact imaging approach based on diffuse optical spectroscopy principles that employs patterned illumination. MI enables rapid quantitative determination of the optical properties over a wide field-of-view. When combined with multi-spectral imaging, MI can quantify in-vivo concentrations of chromophores that are relevant to flap health, namely, oxy- and deoxy-hemoglobin and water concentration. We present results of a preliminary in-vivo MI study using a rodent dorsal skin pedicle flap model. This allowed us to evaluate the feasibility of MI to deduce spatially resolved maps of tissue hemoglobin, oxygenation and hydration. Here we propose that MI can be used for quantitative assessment of flaps in response to vascular occlusion and reperfusion with the aid of hypertonic-hyperoncotic saline solutions. The results of the proposed research will inform further investigations involving MI within the domain of tissue transfer flaps, with the ultimate objective of developing and deploying this technology in the clinical domain. PUBLIC HEALTH RELEVANCE: The use of tissue transfer flaps is a method of moving tissue from a donor location to recipient location and re-attaching the arteries & veins to the blood vessels at the recipient site. This type of reconstructive surgery is subject to failure however, which may include complications due to ischemia-reperfusion injury and vascular insufficiency. We propose to test a new imaging device that will have the capability to guide reconstructive surgery and post-surgical recovery, both reducing post-surgery morbidity and reducing uncertainty in flap healing. Ultimately, if shown to be effective, this technology may lead to reduced duration of hospital stay and concomitant heath care costs in addition to improving surgical outcomes.