EFFECT OF FLUOSOL-DA ON INFARCT MORHOLOGY & ARRHYTHMIAS

FLUOSOL-DA 对梗死形态的影响

• 批准号: 3346665
• 负责人: Renu Virmani
• 金额: $ 5.75万
• 依托单位: AMERICAN REGISTRY OF PATHOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1987-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346665
• 关键词: atherosclerosis; capillary bed; cardiotonic agents; electrocardiography; electron microscopy; electrophysiology; epicardial mapping; fluorocarbon polymers; heart contraction; heart imaging /visualization /scanning; heart motion; heart pharmacology; histology; myocardial infarct sizing; myocardial infarction; sudden cardiac death; ventricular fibrillation

Perfluorochemicals (PFC) have extensive clinical application because these compounds have shown to be effective in transporting oxygen and carbon dioxide. We will assess the effects of PFC therapy on myocardial infarction (MI), ventricular function and ventricular arrhythmias following temporary and permanent coronary artery occlusion at 1, 3 nd 7 days post MI. Dogs will undergo left anterior descending coronary artery occlusion and will be divided into 3 groups. Group I will receive Fluosol-DA (40 ml/Kg) while a similar volume of blood is withdrawn. Group II, sham dogs, will receive a similar volume of their own heparinized blood. Both these groups will be ventilated with 100% O2. Group III, control dogs, will undergo coronary occlusion but no infusion or withdrawal of blood. These dogs will be ventilated with room air. Dogs will be studied 24 hrs after myocardial infarction to determine and characterize the location of ventricular arrhythmias. Ventricular fibrillation threshold (VFT) will be determined and programmed electrical stimulation (PES) will be performed before and 3 and 7 days after infarction to determine what effects PFC may have on these indicies of ventricular vulnerability. Myocardial function will be evaluated by radionuclide ventriculography 1 day before and 1, 3 and 7 days after myocardial infarction. Dogs will be sacrificed at 1, 3 and 7 days and the vascular slices. The area of central necrosis and the border or marginal zones will be defined by light microscopy, mapped and measured. These areas will be compared in each of the groups and correlated with inducibility of ventricular arrhythmias. The mechanism of action of PFC's is not well understood and is probably multifunctional. To elucidate complement as a possible mechanism C1 C3, C4, C5 and CH50 will be measured before and 1,2,6 and 24 hours after myocardial infarction and will be correlated with the extent of inflammatory response seen in the area of infarction. It is postulated that if perfluorochemical, Fluosol-DA treatment, leads to uniform reduction in infarct size, then sustained ventricular tachycardia and/or ventricular fibrillation may be more difficult to induce. However, if perfluorochemical treatment promotes or enhances the marginal zone of infarction in an evolving myocardial infarct, then inducibility of sustained ventricular tachycardia may enhanced. It is anticipated that the results of this study will further our long-term goal to understand the complex relationships which exists between infarct size, infarct metamorphosis and susceptibility to life-threatening ventricular arrhythmias. Our data should provide important information needed for the rational use of perfluorochemical, Fluosol-DA, as clinical therapy in myocardial infarction.

全氟化合物（PFC）具有广泛的临床应用，因为它们 化合物已被证明可以有效运输氧气和碳 二氧化碳。 我们将评估 PFC 治疗对心肌的影响 梗塞 (MI)、心室功能和室性心律失常 术后第 1 天、第 3 天和第 7 天进行临时和永久冠状动脉闭塞 米。 狗将接受左冠状动脉前降支闭塞术 并将分为3组。 第一组将接受 Fluosol-DA（40 ml/Kg），同时抽取相似体积的血液。 第二组，假狗， 将接受类似量的自己的肝素化血液。 这两个 各组将使用 100% O2 进行通风。 第三组，对照狗，将 进行冠状动脉闭塞但不输注或抽血。 这些 狗将通过室内空气进行通风。 24小时后将对狗进行研究 心肌梗死的确定和特征描述 室性心律失常。 心室颤动阈值 (VFT) 为 将执行确定和编程的电刺激（PES） 梗死前以及梗塞后 3 天和 7 天以确定 PFC 可能产生的影响 具有心室脆弱性的这些指标。 心肌功能 将在前 1 天和第 1、3 天通过放射性核素心室造影进行评估 以及心肌梗塞后7天。 狗将在 1、3 点被处死 7天和血管切片。 中央坏死区和 边界或边缘区域将通过光学显微镜、绘图和 测量。 这些领域将在每个组中进行比较 与室性心律失常的诱发性相关。 其机制为 PFC 的作用尚不清楚，可能是多功能的。 到 阐明补体作为可能的机制 C1 C3、C4、C5 和 CH50 将 心肌梗塞发生前及发生后1、2、6、24小时进行测量，并将 与该区域的炎症反应程度相关 梗塞。 据推测，如果全氟化合物，Fluosol-DA 治疗，导致梗塞面积均匀缩小，然后持续 室性心动过速和/或室颤可能更常见 很难诱导。 然而，如果全氟化学处理促进或 增强正在发展的心肌梗塞中的梗塞边缘区， 那么持续性室性心动过速的诱发性可能会增强。 这是 预计这项研究的结果将进一步推动我们的长期目标 了解梗死面积之间存在的复杂关系， 梗死变态和危及生命的心室易感性 心律失常。 我们的数据应该提供所需的重要信息 合理使用全氟化合物 Fluosol-DA 作为临床治疗 心肌梗塞。

项目成果

Myocardial reperfusion injury. Histopathological effects of perfluorochemical.

• 发表时间: 1990-03
• 期刊: Circulation
• 影响因子: 37.8
• 作者: R. Virmani;M. Forman;F. Kolodgie

Effect of perfluorochemical (Fluosol-DA) on infarct morphology in dogs.

全氟化合物（Fluosol-DA）对狗梗塞形态的影响。

• DOI: 10.1007/bf02889896
• 发表时间: 1985
• 期刊: Virchows Archiv. B, Cell pathology including molecular pathology
• 作者: Kolodgie,FD;Dawson,AK;Forman,MB;Virmani,R
• 通讯作者: Virmani,R

Effect of Fluosol-DA on infarct morphology and vulnerability to ventricular arrhythmia.

Fluosol-DA 对梗死形态和室性心律失常易感性的影响。

• DOI: 10.1016/0002-8703(86)90348-0
• 发表时间: 1986
• 期刊: American heart journal
• 影响因子: 4.8
• 作者: Kolodgie,FD;Dawson,AK;Roden,DM;Forman,MB;Virmani,R
• 通讯作者: Virmani,R

Myocardial protection by perfluorochemical infusion during transient ischemia produced by balloon coronary occlusion.

在球囊冠状动脉闭塞引起的短暂性缺血期间通过全氟化合物输注对心肌进行保护。

• DOI: 10.1016/0002-8703(88)90614-x
• 发表时间: 1988
• 期刊: American heart journal
• 影响因子: 4.8
• 作者: Virmani,R;Kolodgie,FD;Osmialowski,A;Zimmerman,P;Mergner,W;Forman,MB
• 通讯作者: Forman,MB

Preservation of endothelial cell structure and function by intracoronary perfluorochemical in a canine preparation of reperfusion.

在犬再灌注准备中通过冠状动脉内全氟化物保存内皮细胞结构和功能。

• DOI: 10.1161/01.cir.76.2.469
• 发表时间: 1987
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Forman,MB;Puett,DW;Bingham,SE;Virmani,R;Tantengco,MV;Light,RT;Bajaj,A;Price,R;Friesinger,G
• 通讯作者: Friesinger,G