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: 7071704
• 负责人: JAMES D REYNOLDS
• 金额: $ 32.08万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7071704
• 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.

本项目的主要目的是评估硝酸乙酯减轻二氧化碳气腹期间组织灌注减少和呼吸性酸中毒的能力。这项研究将使用一种新的药物递送方法：在注入气体中加入硝酸乙酯。腹腔镜手术已迅速成为外科干预纠正腹部病理的首选方法。然而，充气腹膜，即向腹膜腔内注入气体的行为，并非没有生理后果：肺功能受损，器官血流改变。此外，由于其在血浆中的溶解度，注入CO2会增加pCOz并降低血液pH值，从而导致呼吸性酸中毒、心动过速和心律失常。在存在潜在血管疾病的情况下，在老年人中，如果患者怀孕，和/或手术时间延长时，总体影响可能会变得深刻。在所有情况下，组织缺血和胎儿缺血（如适用）可产生显著的发病率。为了控制这种情况，一个合乎逻辑的假设是，使用血管活性药物来增加组织血液流动和气体交换将是有益的。为了本研究的目的，我们建议在充气气体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局部作用（即在腹膜内），也可以进入体循环，在妊娠患者的情况下，进入胎儿循环（通过扩散或母胎交换），这似乎是一种理想的方法，以减轻CO2在腹膜内介导的生理状态变化。这样的缓解预计将是长期受益于所有腹腔镜患者，包括产妇和胎儿。为了评估这种新疗法，我们将检验两个研究假设：

项目成果

Maternal insufflation during the second trimester equivalent produces hypercapnia, acidosis, and prolonged hypoxia in fetal sheep.

妊娠中期期间母体充气会导致胎羊出现高碳酸血症、酸中毒和长时间缺氧。

• DOI: 10.1097/00000542-200412000-00013
• 发表时间: 2004
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Uemura,Kenichiro;McClaine,RebeccaJ;delaFuente,SebastianG;Manson,RobertoJ;Campbell,KurtA;McClaine,DeborahJ;White,WilliamD;Stamler,JonathanS;Eubanks,WSteve;Reynolds,JamesD
• 通讯作者: Reynolds,JamesD

Inclusion of an S-nitrosylating agent in the insufflating gas does not alter gastric activity in rats following pneumoperitoneum.

在吹入的气体中包含S-亚硝基化剂不会改变气腹后大鼠的胃活动。

• DOI: 10.1007/s00464-006-9107-6
• 发表时间: 2007
• 期刊: Surgical endoscopy
• 作者: Shah,MK;Shimazutsu,K;Uemura,K;Takahashi,T;Stamler,JS;Reynolds,JD
• 通讯作者: Reynolds,JD

Inclusion of a nitric oxide congener in the insufflation gas repletes S-nitrosohemoglobin and stabilizes physiologic status during prolonged carbon dioxide pneumoperitoneum.

• DOI: 10.1111/j.1752-8062.2009.00154.x
• 发表时间: 2009-12
• 期刊: Clinical and translational science
• 作者: Shimazutsu K;Uemura K;Auten KM;Baldwin MF;Belknap SW;La Banca F;Jones MC;McClaine DJ;McClaine RJ;Eubanks WS;Stamler JS;Reynolds JD
• 通讯作者: Reynolds JD