EVALUATION OF RETROVENOUS DRUG DELIVERY SYSTEM

逆行给药系统的评价

• 批准号: 3508523
• 负责人: JEFFREY L PETERS
• 金额: $ 29.85万
• 依托单位: UBTL, INC.
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3508523
• 关键词: aortic balloon pump; biomaterial development /preparation; biomedical equipment safety; cardiotonic agents; catheterization; clinical biomedical equipment; coronary occlusion /thrombosis; coronary sinus; disease /disorder model; dogs; dosage; drug administration routes; drug adverse effect; drug delivery systems; fibrinolytic therapy; heart circulation; heart disorder chemotherapy; heart disorder diagnosis; heart pharmacology; heart surgery; histopathology; lidocaine; myocardial infarction; myocardial ischemia /hypoxia; nonhuman therapy evaluation; perfusion; pharmacokinetics; plasminogen activator; sheep; ventricular fibrillation; aortic balloon pump; biomaterial development /preparation; biomedical equipment safety; cardiotonic agents; catheterization; clinical biomedical equipment; coronary occlusion /thrombosis; coronary sinus; disease /disorder model; dogs; dosage; drug administration routes; drug adverse effect; drug delivery systems; fibrinolytic therapy; heart circulation; heart disorder chemotherapy; heart disorder diagnosis; heart pharmacology; heart surgery; histopathology; lidocaine; myocardial infarction; myocardial ischemia /hypoxia; nonhuman therapy evaluation; perfusion; pharmacokinetics; plasminogen activator; sheep; ventricular fibrillation

A novel retrovenous myocardial drug delivery system has been developed and Phase I feasibility demonstrated in sheep with acute LAD coronary artery occlusion. Control sheep with intravenous lidocaine therapy developed ventricular fibrillation in a mean time of 12.5 minutes after PTCA-LAD occlusion. In contrast, retrovenously treated sheep with an identical lidocaine dose and venous blood survived prolonged study periods to 3 hours despite infarction in the area-at-risk, severe ECG changes, and myocardial depression. Phase II work will determine the efficacy of combined retrovenous arterialized blood and lidocaine for prevention of arrhythmias and salvage of ischemic myocardium. A dose-response of retrovenous lidocaine after coronary artery occlusion will be obtained. Four-lumen retrovenous catheters will be fabricated and tested to evaluate our hypothesis that recirculation of therapeutic agents via the coronary sinus reduces the effective dose and thus the proarrhythmic or toxic effects of the therapeutic agents. A second hypothesis will be tested in a model of acute coronary thrombosis that retrovenous t-PA thrombolytic therapy by itself or in combination with selective arterial or intravenous therapy accelerates clot lysis and time of myocardial reperfusion. The retrovenous drive system developed during Phase I will be modified for controlled drug delivery with safeguards and alarms for Phase III clinical application.

一种新型逆转的心肌输送系统 与 急性LAD冠状动脉阻塞。 控制绵羊 静脉L，利多卡因治疗发展 PTCA-LAD闭塞后的平均时间为12.5分钟。 在 对比，用相同的利多卡因逆转处理的绵羊 剂量和静脉血液在长时间的研究期内幸存到3小时 尽管在风险区域中梗塞，但ECG的严重变化，并且 心肌抑郁症。 第二阶段的工作将确定功效 联合逆转动脉化血液和利多卡因 预防心律不齐和缺血心肌的挽救。 冠状动脉后逆转录子因的剂量反应 将获得阻塞。 四亮倒载导管将 进行制造和测试以评估我们的假设 通过冠状窦再循环治疗剂减少 有效剂量，因此是心律失常或毒性的作用 治疗剂。 第二个假设将在 急性冠状动脉血栓形成的模型 溶栓疗法本身或与选择性结合 动脉或静脉治疗会加速凝块溶解和时间 心肌再灌注。 在第一阶段开发的逆转驱动系统将是 通过保障措施和警报修改用于控制药物输送 用于III期临床应用。