Experimental coronary artery occlusion and reperfusion

Unstable angina pectoris, acute myocardial infarction, sudden coronary death, but also the application of coronary angioplasty, are all characterized by acute coronary arterial damage, activation of platelets and the coagulation cascade, liberation of vasoactive substances and growth factors. During the last decade, the increased application of thrombolytic therapy and percutaneous coronary angioplasty have provided us with better clinical results, but also with new problems. The prevention of thrombotic occlusion, the efficacy of arterial recanalization, as well as the prevention of early reocclusion and later restenosis are all subject to increased research efforts. In the present thesis a model of thrombotic coronary occlusion has been described. In this model it was demonstrated that two experimental drugs, the stable prostacyclin analogue iloprost and the thromboxane receptor blocker solutroban, may be useful for clinical testing to prevent this potentially life-threatening event. Using the same animal model for coronary thrombosis, it was shown that the addition of the calcium antagonist nifedipine to a thrombolytic agent, improves myocardial perfusion in the acute phase of thrombolytic coronary recanalizatio

The selective bradycardic effects of zatebradine (UL-FS 49) do not adversely affect left ventricular function in conscious pigs with chronic coronary artery occlusion

Summary This study was designed to test whether the selective bradycardic effects of zatebradine (UL-FS 49) were altered in the setting of chronic mild left ventricular dysfunction secondary to a myocardial infarction. We therefore administered four doses of UL-FS 49 at 15-min intervals (cumulative doses of 10, 30, 100, and 300 μg/kg) to eight normal conscious pigs and to seven pigs in which the left circumflex coronary artery was occluded 3 weeks previously. Left ventricular dysfunction in this second group of animals was manifested by an increase in left ventricular end-diastolic pressure (LVEDP 11±2 mmHg vs. 7±1 mmHg, respectively; p<0.05) and a decrease in LVdP/dtmax (3020±210 mmHg vs. 3720±210 mmHg, respectively; p<0.05). The results showed that UL-FS 49 was equally effective in reducing heart rate in both groups of animals [from 126±4 to 95±2 beats/min and from 140±5 to 98±6 beats/min for the normal animals and for the animals with a chronic myocardial infarction (MI), respectively]. The duration of left ventricular systole was not affected, but the duration of diastole was prolonged from 290±10 msec to 420±20 msec in the normal animals and from 250±10 msec to 430±30 msec in the animals with MI (both p<0.05). Up to 100 μg/kg UL-FS 49 did not affect arterial blood pressure, whereas LVdP/dtmax and cardiac output decreased by less than 10% in either group. With the highest dose there were decreases in cardiac output (20%) and LVdP/dtmax (15%) and a 5–6 mmHg increase in left ventricular end-diastolic pressure in both groups. The data suggest that UL-FS 49 in doses up to 100 μg/kg may also, in the setting of chronic mild left ventricular dysfunction, be an attractive agent when heart rate has to be reduced selectively

Benestent II: Back to the future

It has been shown repeatedly in animal and clinical studies that heparin coating reduces thrombotic complications of several surfaces in contact with flowing blood. The demonstration that implantation of heparin-coated coronary stents is also effective in prevention of subacute thrombotic occlusion in a pig model offers the persp

Endothelialization of Intravascular Stents

Wide clinical application of intravascular stenting devices is currently limited by occlusion or intraluminal narrowing caused by thrombosis and neointimal thickening in a considerable percentage of implantations. We studied the possibility of seeding one of the currently availiable stents, a stainless steel, self‐expandable wire‐mesh, with endothelial cells in vitro. Endothelial cells, derived from human umbilical cord veins, could be successfully attached to stent filaments. In vivo stent implantations in porcine femoral arteries showed complete covering of stent wires by endothelium after 1 week. We conclude that coating of stents with autologous endothelial cells prior to implantation might protect against early thrombosis during the period in which a neointima is formed. (J Interven Cardiol 1988:1:2) Copyrigh

Stenting or balloon angioplasty of stenosed autologous saphenous vein grafts in pigs

In a model of early and aggressive vein graft stenosis in pigs, an intervention was performed with a single stent (n = 12 grafts), multiple stents (n = 6), or balloon angioplasty (n = 6), while grafts with mild stenoses were left untreated (n = 8). Four weeks after intervention, angiography showed that grafts with single stents, balloon angioplasty, or untreated grafts had patency rates of 92%, 83%, and 83%, respectively. Grafts receiving multiple stents, however, showed only a 17% patency rate (p < 0.05). Balloon dilatation or placement of a single stent improved the angiographic minimal diameter by 0.6 ± 0.2 and 0.8 ± 0.3 mm, respectively, over the short term, but this gain was lost during the follow-up period. Multiple stents showed a similar gain (0.5 ± 0.2 mm) but more loss occurred during the follow-up period (2.4 ± 0.2 mm). Histology revealed no significant differences between the treatment groups except for the prolonged presence of thrombus remnants in association with the stent wires. In conclusion, single stents and balloon angioplasty show good patency in early saphenous vein graft narrowing but multiple stents show a high occlusion rate

Can the same edge-detection algorithm be applied to on-line and off-line analysis systems? Validation of a new cinefilm-based geometric coronary measurement software

In the Cardiovascular Measurement System (CMS) the edge-detection algorithm, which was primarily designed for the Philips digital cardiac imaging system (DCI), is applied to cinefilms. Comparative validation of CMS and DCI was performed in vitro and in vivo with intracoronary insertion of stenosis phantoms in anesthetized pigs. The "obstruction diameter" (OD) was measured at the artificial stenoses visualized by angiography with calibration at the isocenter (ISO) and catheter calibration (CATH) and compared with the true phantom diameters. A clinical comparison of OD, reference diameter (RD), and percentage diameter stenosis (DS) was performed on 70 corresponding images from post-PTCA angiograms. In vitro, OD (CMS) yielded an accuracy of 0.18 +/- 0.14 mm with 100% (correlation coefficient: r = 0.97, y = 0.06 + 0.75x, standard error of estimate [SEE] = 0.09) and 0.19 +/- 0.15 mm with 50% contrast (r = 0.94, y = 0.02 + 0.81 x). OD (DCI) yielded an accuracy of 0.11 +/- 0.06 mm with 100% (r = 0.99, y = -0.03 + 0.91 x, SEE = 0.05) and 0.24 +/- 0.13 mm with 50% contrast (r = 0.94, y = 0.29 + 6.69 x, SEE = 0.12). In vivo, OD (CMS) yielded an accuracy of 0.18 +/- 0.23 mm with ISO (r = 0.89, y = 0.02 + 0.83 x, SEE = 0.22) and 0.26 +/- 0.24 mm with CATH (r = 0.89, y = 0.06 + 0.72 x, SEE = 0.19). OD (DCI) yielded an accuracy of 0.08 +/- 0.15 mm with ISO (r = 0.96, y = 0.08 + 0.86 x, SEE = 0.14) and 0.18 +/- 0.21 mm with CATH (r = 0.92, y = 0.09 + 0.76 x, SEE = 0.17). The clinical comparison showed reasonable agreement for OD only (r = 0.81, y = 0.26 + 0.81 x, SEE = 0.29). Transformation of an edge-detection algorithm from a digital to a cinefilm-based system can lead to impairment of measurement reliability