Gene Therapy with Vascular Endothelial Growth Factor for Inoperable Coronary Artery Disease: Anesthetic Management and Results
Gene Therapy with Vascular Endothelial Growth Factor for Inoperable Coronary Artery Disease: Anesthetic Management and Results
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DOI：
10.1097/00000539-200101000-00005
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发表时间：
2001-01
影响因子：
5.7
通讯作者：
K. Lathi;P. Vale;Douglas Losordo;R. M. Cespedes;J. Symes;D. Esakof;M. Maysky;J. Isner
中科院分区：
文献类型：
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作者：
K. Lathi;P. Vale;Douglas Losordo;R. M. Cespedes;J. Symes;D. Esakof;M. Maysky;J. Isner
用于治疗性血管生成的基因转移代表了一种新的治疗药物难治性心绞痛的患者判断不适合进一步的传统血运重建。我们描述了30例3级或4级心绞痛患者的麻醉管理，这些患者参加了1期临床试验，以评估裸DNA编码血管内皮生长因子（phVEGF 165）直接心肌基因转移作为难治性心绞痛的唯一疗法的安全性和生物活性。通过小切口将phVEGF 165直接注射到心肌中。所有患者都有围手术期心脏不良并发症的主要临床预测因素。使用瑞芬太尼和地氟烷的快速通道麻醉管理、多模式镇痛以及硝酸甘油和艾司洛尔的积极血流动力学控制。所有患者均能耐受麻醉和手术，无任何问题。无围手术期心肌梗死、血流动力学不稳定或心力衰竭发生。VEGF注射未引起心血管功能的临床显著变化。平均住院时间为3.8天。有1例晚期死亡（术后5个月）。30例患者中有29例心绞痛发作次数减少（术前56.2 ± 4.1次/周vs术后3.8 ± 1.6次/周，P < 0.0001），舌下含服硝酸甘油减少（术前60.1 ± 4.4片/周vs术后2.9 ± 1.1片/周，P < 0.0001）。以前接受过血运重建的患者现在被判定为“不可手术”，继续表现为慢性复发性心绞痛。我们的研究描述了一种新的方法，通过使用基因治疗，刺激血管生成和改善缺血心肌灌注的麻醉考虑和管理这样的病人。
Gene transfer for therapeutic angiogenesis represents a novel treatment for medically intractable angina in patients judged not amenable to further conventional revascularization. We describe the anesthetic management of 30 patients with class 3 or 4 angina, enrolled in a Phase 1 clinical trial to assess the safety and bioactivity of direct myocardial gene transfer of naked DNA-encoding vascular endothelial growth factor (phVEGF165), as sole therapy for refractory angina. The phVEGF165 was injected directly into the myocardium through a mini-thoracotomy. All patients had major clinical predictors for adverse perioperative cardiac complications. Fast-track anesthetic management with remifentanil and desflurane, multimodal analgesia, and aggressive hemodynamic control with nitroglycerin and esmolol were used. All patients tolerated anesthesia and surgery without problems. No perioperative myocardial infarction, hemodynamic instability, or ventricular failure occurred. VEGF injections caused no clinically significant changes in cardiovascular function. Mean hospital stay was 3.8 days. There was one late death (5 months postoperative). Twenty-nine of 30 patients experienced reduced angina (56.2 ± 4.1 episodes/week preoperatively versus 3.8 ± 1.6 postoperatively, P < 0.0001) and reduced sublingual nitroglycerin consumption (60.1 ± 4.4 tablets/week preoperatively versus 2.9 ± 1.1 postoperatively, P < 0.0001). IMPLICATIONS Previously revascularized patients now judged “inoperable,” continue to present with chronic, recurrent angina. Our study describes the anesthetic considerations and management of such patients treated with a novel approach by using gene therapy to stimulate angiogenesis and improve perfusion to ischemic myocardium.