Utilizing Ethyl Nitrate Gas in Laparoscopic Surgery

在腹腔镜手术中使用硝酸乙酯气体

• 批准号: 6613133
• 负责人: JAMES D REYNOLDS
• 金额: $ 33.68万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6613133
• 关键词: acidity /alkalinity; apoptosis; birth; blood chemistry; carbon dioxide; chromatography; flow cytometry; gas; histology; immunocytochemistry; intestine disorder; laparoscopy; nitrates; nitric oxide; perfusion; peritoneum; pregnancy circulation; respiratory acidosis; respiratory gas level; sheep; surgery; swine; terminal nick end labeling; vasoactive agent

The principal goal of this project is to evaluate the ability of ethyl nitrate to attenuate the reduced tissue perfusion and respiratory acidosis produced during carbon dioxide pneumoperitoneum. The studies will use a novel method of drug delivery: inclusion of ethyl nitrate in the insufflating gas. Laparoseopy has rapidly become the method of choice for surgical intervention to correct abdominal pathologies. However, pneumoperiteneum, the act of insufflating the peritoneal cavity with gas, is not without physiologic consequence: pulmonary function is impaired and organ blood flows altered. In addition, due to its plasma solubility, insufflation with CO2 will increase pCOz and decrease blood pH, actions that can produce respiratory acidosis, tachycardia, and arrhythmia. The overall effects can become profound in the presence of underlying vascular disease, in[ the elderly, if the patient is pregnant, and/or when the duration of surgery is extended. In all situations, tissue ischemia and fetal ischemia (where applicable) can produce significant morbidity. To control this, it is a logical supposition that administration of a vasoactive agent to increase tissue blood flow and gas exchange would be beneficial. For the purposes of this study, we propose to introduce a nitric oxide donator (ethyl nitrate; E-NO) into the insufflating gas. As the released nitric oxide can act locally (i.e. within the peritoneum) as well as entering the systemic circulation and, in the case of the gravid patient, the fetal circulation (either by diffusion or maternal-fetal exchange), this would appear to be an ideal methodology to abate the CO2 pnenmoperiteneum-mediated changes in physiologic status. Such abatement is expected to be of long-term benefit to all laparoscopic patients including the parturient and her fetus. To evaluate this novel therapy, we will test two research hypotheses: 1. In the non-gravida, inclusion of E-NO in the insufflating gas attenuates the tissue perfusion changes produced by CO2 pneumoperitoneum; and 2. In the parturient, inclusion of E-NO during maternal pneumoperitoneum stabilizes fetal physiologic status. Studies will utilize adult swine and pregnant sheep. Completion of this investigation will produce clinically-relevant information that will be of significant interest to surgeons With patients in need of laparoscopic surgery and to obstetricians who are presented with parturients in abdominal distress. It is expected that the results of these studies will be used to further develop and refine standards of care for human laparoscopy and will lead to a novel therapy for controlling the blood flow changes produced during pneumoperitoneum.

该项目的主要目标是评估硝酸乙酯减轻二氧化碳气腹期间组织灌注量减少和呼吸性酸中毒的能力。这些研究将使用一种新的药物输送方法：在吸入的气体中加入硝酸乙酯。腹腔镜术已迅速成为外科干预纠正腹部病变的首选方法。然而，气腹，即向腹膜腔内注入气体的行为，并不是没有生理后果：肺功能受损，器官血流改变。此外，由于二氧化碳在血浆中的溶解性，注入二氧化碳会增加二氧化碳分压，降低血液pH值，从而导致呼吸性酸中毒、心动过速和心律失常。如果存在潜在的血管疾病，[老年人，如果患者怀孕，和/或延长了手术时间]，总体影响可能会变得非常严重。在所有情况下，组织缺血和胎儿缺血(在适用的情况下)都可以产生显著的发病率。为了控制这种情况，合乎逻辑的假设是，使用血管活性物质来增加组织血流量和气体交换将是有益的。为了这项研究的目的，我们建议在喷气中引入一氧化氮供体(硝酸乙酯；E-NO)。由于释放的一氧化氮可以在局部(即在腹膜内)发挥作用，并进入体循环，对于孕妇来说，还可以进入胎儿循环(通过扩散或母胎交换)，这似乎是减轻二氧化碳腹膜下介导的生理状态变化的理想方法。这种减轻预计将对所有的腹腔镜患者，包括产妇和她的胎儿都有长期的好处。为了评估这种新疗法，我们将检验两个研究假设： 1.在非孕妇中，在气腹中加入E-NO可以减轻CO2气腹引起的组织灌注量的变化；2.在产妇中，在母体气腹中加入E-NO可以稳定胎儿的生理状态。研究将利用成年猪和怀孕的绵羊。这项研究的完成将产生与临床相关的信息，这些信息将对需要进行腹腔镜手术的外科医生和出现腹部窘迫的产妇的产科医生产生重大兴趣。预计这些研究的结果将被用于进一步发展和完善人类腹腔镜术的护理标准，并将导致一种控制气腹期间血流变化的新疗法。