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: 6919234
• 负责人: JAMES D REYNOLDS
• 金额: $ 34.65万
• 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/6919234
• 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.

该项目的主要目的是评估硝酸乙酯减轻二氧化碳肺炎碳中产生的减少组织灌注和呼吸酸中毒的能力。该研究将使用一种新型的药物输送方法：将硝酸乙酯纳入不足的气体中。腹腔镜已迅速成为手术干预以纠正腹部病理学的选择方法。然而，气质是用气体脱落腹膜腔的行为，并非没有生理后果：肺功能受损，器官血液流动改变。此外，由于其血浆溶解度，二氧化碳的不足将增加PCOZ并降低血液pH值，可产生呼吸酸中毒，心动过速和心律不齐的作用。在存在潜在的血管疾病的情况下，在[老年人，如果患者怀孕和/或延长手术持续时间时。在所有情况下，组织缺血和胎儿缺血（在适用的情况下）都会产生明显的发病率。为了控制这一点，这是一种逻辑上的假设，即给药以增加组织血流和气体交换是有益的。为了本研究的目的，我们建议将一氧化氮捐赠者（硝酸乙酯； E-NO）引入不合适的气体中。由于释放的一氧化氧化物可以在本地起作用（即腹膜内），并输入系统循环，并且在妊娠患者的情况下，胎儿循环（通过扩散或孕产妇交换）似乎是一种理想的方法，可以减轻CO2 PNENMOPERITENEMEDENEMEDENEMEDENEMEDENEMEDENEMEDENEMEDENEMEDENEMED介导的物理学状态。预计这种减排对包括分离率和她的胎儿在内的所有腹腔镜患者具有长期益处。为了评估这种新型疗法，我们将检验两个研究假设： 1。在非gravida中，将电子-NO纳入不足的气体中会减弱二氧化碳肺炎的组织灌注变化；和2。在分娩中，在母体气tone骨期间纳入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。这项调查的完成将产生与需要腹腔镜手术的患者以及在腹部困扰中伴有分娩者的产科医生有关的外科医生，这将引起与临床相关的信息。预计这些研究的结果将用于进一步开发和完善人腹腔镜的护理标准，并将导致一种新的疗法来控制肺炎药物期间产生的血液流动变化。