Tessmer John P, Pagel Paul S, Weihrauch Dorothee, Ludwig Lynda M, Chilian William M, Kersten Judy R, Warltier David C
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
J Pharmacol Toxicol Methods. 2002 Mar-Apr;47(2):73-8. doi: 10.1016/s1056-8719(02)00220-4.
Coronary collateral development is an important adaptive response to chronic myocardial ischemia. Characterization of mitogenic factors responsible for collateral formation has been an elusive goal because these substances are difficult to sample from the myocardial interstitium at multiple times. We report the implantation of an exchange catheter capable of in vivo sampling of myocardial interstitial fluid in chronically instrumented dogs.
The catheter consisted of multiple perforations within a 2-cm segment of Micro-Renathane tubing that was implanted into the left ventricular myocardium between the left anterior descending (LAD) and left circumflex coronary artery (LCCA) perfusion territories and secured to the epicardium with a Silastic disk. Dogs (n=5) underwent brief (2 min) LAD occlusions once per hour, 8 times/day, 7 days/week for 2 weeks to stimulate coronary collateral growth. Another group of dogs (n=6) without repetitive coronary occlusions served as controls. Myocardial interstitial fluid was collected daily, and mitogenic activity was evaluated by the proliferative responses of growth-arrested, cultured vascular smooth muscle and endothelial cells.
All dogs tolerated catheter implantation without complication. Each catheter functioned well throughout the duration of the experiment. Myocardial interstitial fluid obtained using the exchange catheter in this model of repetitive coronary occlusion produced marked proliferation of vascular smooth muscle and endothelial cells in vitro.
The exchange catheter enables chronic in vivo sampling of myocardial interstitial fluid and may facilitate identification of mitogens involved in coronary collateral development.
冠状动脉侧支循环的发展是对慢性心肌缺血的一种重要适应性反应。由于这些物质难以在多个时间点从心肌间质中取样，因此确定负责侧支形成的促有丝分裂因子一直是一个难以实现的目标。我们报告了一种交换导管的植入，该导管能够在长期植入仪器的犬体内对心肌间质液进行取样。
该导管由一段2厘米长的微型聚氨酯管内的多个穿孔组成，该管被植入左心室心肌中，位于左前降支（LAD）和左旋支冠状动脉（LCCA）灌注区域之间，并用硅橡胶盘固定在心外膜上。犬（n = 5）每小时接受一次短暂（2分钟）的LAD闭塞，每天8次，每周7天，持续2周，以刺激冠状动脉侧支生长。另一组犬（n = 6）不进行重复性冠状动脉闭塞作为对照。每天收集心肌间质液，并通过生长停滞的培养血管平滑肌和内皮细胞的增殖反应评估促有丝分裂活性。
所有犬均耐受导管植入，无并发症。在整个实验过程中，每个导管功能良好。在这种重复性冠状动脉闭塞模型中，使用交换导管获得的心肌间质液在体外可使血管平滑肌和内皮细胞显著增殖。
交换导管能够对心肌间质液进行慢性体内取样，并可能有助于识别参与冠状动脉侧支循环发展的促有丝分裂原。
