Hong-De Wu

Healing Basis and Surgical Techniques for Complete Revascularization of the Left Ventricle Using Only the Internal Mammary Arteries

Long-term follow-up data from several leading centers concerning patients undergoing coronary artery bypass clearly demonstrate the superiority of the internal mammary artery (IMA) with patency rates of 83 to 94% at 7 to 12 years compared with the saphenous vein and its patency rates of 41 to 53%. Our experimental studies provide a biological basis for understanding this difference. Thin-walled arterial autografts undergo no histological change after being implanted in the arterial system, while venous autografts undergo major changes with an initial scattered loss of endothelium and marked thickening due to a proliferative reaction. The challenge to the cardiac surgeon is to revascularize the entire left ventricle with the IMAs. We have found this possible in most patients with advanced three-vessel disease by using both IMAs either as in situ grafts or free grafts with as many sequential anastomoses as necessary to achieve full revascularization. Our use of the term in situ refers to the grafts origin from the subclavian artery as opposed to a free IMA graft arising from another site.

Experimental evaluation of ten clinically used arterial prostheses

The arterial grafts currently in use are classified into five basic categories; 10 different commercially available prostheses were chosen to represent these categories. The Vascutek and Bionit are made from knitted Dacron and have medium porosity, requiring preclotting by the surgeon. The DeBakey Soft Woven and Plasma TFE grafts are made from woven Dacron and have low porosity, not requiring preclotting under most circumstances. Also studied were woven and knitted grafts with leakage resistance referred to as “impervious” Dacron grafts: the Vascutek Gelseal, the Bard Albumin Coated DeBakey Vasculour II, the Microvel with Hemashield, and the albumin saturated, autoclaved DeBakey Soft Woven graft. Gore-Tex and Impra are expanded polytetrafluoroethylene grafts which do not require preclotting. For each type, five grafts 6 cm long and 8 mm in diameter were implanted in the descending thoracic aorta of healthy adult dogs for 16 weeks. The physical characteristics, biocompatibility, and healing patterns varied according to the structure and treatment of the grafts. Pretreatment with biomaterials during manufacture is quite effective in preventing transinterstices blood loss during implantation, but results in altered physical qualities, increased thrombogenicity and delayed healing in comparison to the effects of preclotting with autogenous blood at the time of implantation.

An experimental study of eight current arterial prostheses

Eight currently used arterial prostheses with differing constructions and materials were implanted in the descending thoracic aorta of mongrel dogs. The prostheses were Gore-Tex (polytetrafluoroethylene), DeBakey Woven, Cooley Woven, Meadox Woven Double Velour, Cooley Knitted Double Velour, Microvel, Vasculour II, and Bionit II. Five series of these eight prostheses were serially implanted in heparinized subjects. During the 40 implantations, attention was focused on three major characteristics: preclotting efficiency, surgical handling characteristics, and healing. Gore-Tex is impervious to blood. The DeBakey and Cooley woven grafts are nearly so. The remaining prostheses required preclotting. The Meadox Woven Double Velour became impervious after two preclotting steps, the Cooley Knitted Double Velour and the Bionit II required three, and the Vasculour II and the Microvel required four. The surgical handling characteristics of the knitted prostheses clearly surpassed those of the DeBakey and Cooley woven and Gore-Tex prostheses. Although the Meadox Woven Double Velour prosthesis had better conformability than the nonveloured woven, the tendency of its cut edge to fray was more pronounced. Healing was much more advanced in the knitted and woven prostheses than in the Gore-Tex.

Differences in reendothelialization after balloon catheter removal of endothelial cells, superficial endarterectomy, and deep endarterectomy

The process of reendothelialization was studied in a deendothelialized 3 cm segment of the canine descending thoracic aorta from which peripheral endothelial cell ingrowth had been prevented by impervious prosthetic graft sleeves. Three preparations were studied: (1) removal of only the endothelial cells, accomplished by flow surface drying and balloon catheter denudation, (2) removal of the superficial portion of the nonvasal media, accomplished by endarterectomy to a depth of 200 to 300 micron, and (3) removal of the entire inner (nonvasal) media, accomplished by endarterectomy to a depth of 500 to 600 micron to reach the outer (vasal) media. A total of 44 specimens were studied after implantation periods of 7, 14, 28, and 56 days. In all cases endothelial cell ingrowth from the host aorta into the test specimen was prevented by the impervious graft sleeves. In the deep endarterectomy group there were scattered areas of reendothelialization at 1 week, extensive reendothelialization at 2 weeks, almost complete reendothelialization at 4 weeks, and confluence by 8 weeks. However, in the superficial endarterectomy group scanning electron microscopy showed scattered areas of factor VIII/von Willebrand factor (FVIII/vWF)-negative, endothelial-like cells at 4 weeks, whereas at 8 weeks most of the surface was covered by endothelial cells identified by FVIII/vWF. In those specimens subjected to balloon catheter removal of endothelial cells only, reendothelialization was not seen, even at 8 weeks.

A comparative experimental study of the organization of arterial and venous thrombi.

Organization of a venous thrombus proceeds much faster than that of an arterial thrombus. Two different double-ligation procedures were used for study of the time sequence of thrombus organization by the vascularized (in situ) and devascularized (dissected) walls of the external jugular vein and common carotid artery in 21 mongrel dogs. Blood in the ligated segments of the in situ veins remained mostly fluid. In these segments, intimal hyperplasia was observed after 4 weeks with apparent preservation of an endothelial lining. However, in the dissected veins, the trapped blood rapidly thrombosed. Remarkable cell proliferation quickly occurred in these dissected walls with rapid invasion of the thrombus to achieve complete organization by 4 weeks. In contrast, a thrombus formed in the ligated segments of all arteries, whether in situ or dissected, and organization was much slower, requiring about 4 months for completion. Full-wall viability was maintained in 100% of the in situ veins and in 95% of the devascularized veins, but inner wall viability was lost in 30% of the in situ arteries and in 95% of the devascularized arteries.

Aspirin therapy in small-caliber arterial prostheses: Long-term experimental observations*

To study the therapeutic effects of 3 mg/kg aspirin given at the time of surgery and postoperatively, Dacron carotid grafts with an internal diameter of 4 mm and a length of 6 cm were implanted bilaterally in mongrel dogs. Sixteen control grafts in eight subjects and 20 grafts in 10 subjects treated with aspirin were followed by serial angiograms until consecutive studies showed stable patency rates in both groups. Platelet aggregations, malondialdehyde production, serum salicylate levels, and thromboxane A2 and prostacyclin secretion (measured as thromboxane B2 and 6-keto-prostaglandin F1 alpha) were monitored prior to and throughout the experiment. Surface mapping, indium-111 uptake, factor VIII-related antigen staining, and scanning and transmission electron microscopy were performed on the grafts at sacrifice. This study demonstrates a protective effect on the early patency of small-caliber prostheses in the canine model with daily oral aspirin administration. The degree and duration of this effect depends on the preoperative baseline ratio of thromboxane to prostacyclin in each subject.

Implant site: a determinant of completeness of arterial prosthesis healing in the dog and possibly in humans.

This paper compares the healing of supported knitted Dacron prostheses implanted in the descending thoracic aorta and in the subcutaneous carotid-femoral positions in each of 10 dogs. The descending thoracic aorta prostheses were 6 cm long and the carotid-femoral prostheses averaged 76 cm in length. The healing of four porous clinical axillofemoral grafts is compared to that of the experimental carotid-femoral grafts. There was little similarity between the healing observed in the descending thoracic aortic and subcutaneous positions; the descending thoracic aorta grafts healed rapidly and completely by eight weeks, with thrombus-free flow surfaces covered with confluent endothelial cells. However, the inner wall of the carotidfemoral grafts remained largely unhealed at one year, with endothelialization largely confined to a limited pannus ingrowth across the anastomoses. This indicates that the implant site in the dog is a primary determinant of the rapidity and completeness of healing. The clinical axillofemoral grafts explanted after 20 months to six and one-half years exhibited healing characteristics that were similar to those seen in the carotid-femoral position in the dog. These findings suggest that valid comparisons of interspecies healing require data obtained from similar implant locations. They present a challenge to the previously held concepts of major interspecies differences in speed and extent of tissue ingrowth based on data obtained from noncomparable implant sites.

Glutaraldehyde preparation of coronary artery bypass bioprostheses

A method for glutaraldehyde (GA) fixation of canine carotid arteries has been developed for the preparation of small caliber biologic prostheses for coronary artery bypass. The biologic grafts were preserved by a static inflation technique that proved to be more advantageous than the standard stenting method. The most suitable static inflation pressure was found to be 120 mm Hg. By means of colorimetric measurements the minimal tanning time and the amount of GA required for complete fixation for canine vascular tissue were established. Stabilization of the vessel collagen and confirmation of GA-collagen cross-linking were verified by evaluation of the elastic properties and shrinkage temperature of the grafts. Stress-strain measurements were evaluated to determine the number of cross-links introduced in the vascular tissue by GA. This number was shown to be proportional to the inflation pressure. Ethyl alcohol was chosen as the storage solution because it maintained the best physical, chemical, and histologic characteristics of the grafts. Biological evaluations were performed with carotid implants that were examined following acute low flow studies and implantations up to 112 days. All implantations have yielded 100% patencies.

Reendothelialization of isolated segments of the canine carotid artery with reference to the possible role of the adventitial vasa vasorum

This study was designed to determine if the adventitial vasa vasorum contribute to re-endothelialization of the canine carotid artery after removal of the endothelial flow surface. Casting studies demonstrated that vasa vasorum are present only in the adventitia of the canine carotid artery. Ninety autograft segments of the carotid artery from which the endothelium had been removed were implanted in both carotid arteries of 45 dogs. Glutaraldehyde-processed canine carotid allografts were positioned at each end to prevent pannus ingrowth and a Gore-Tex wrap to prevent periarterial tissue growth was placed into the outer wall. Three methods were used, with observations at 4 and 8 weeks. In method 1 the test segment was treated with superficial endarterectomy. In method 2 a balloon catheter was used to remove the endothelium. In method 3 balloon catheter denudation of the flow surface was also employed and, in addition, the adventitia was removed surgically as completely as possible, although a few vasa vasorum were shown to remain in some grafts. In method 1 all the patent endarterectomized arteries were partially re-endothelialized at both the 4- and 8-week intervals. In method 2, 72% of the balloon-denuded patent arteries with intact adventitial vasa vasorum were partially re-endothelialized at 4 weeks and 84% at 8 weeks. However, in method 3 the flow surfaces had no endothelium at 4 weeks and 83% still had none at 8 weeks. These findings suggest that, in the absence of pannus ingrowth, re-endothelialization of the canine carotid artery depends on not only the presence but also the number of adventitial vasa vasorum.

The Evolution of a Clinically Relevant Experimental Model for the Realistic Evaluation of Long-Length (80-cm) Arterial Prostheses

A new carotid-femoral experimental model has been developed which has significant clinical relevance to human limb salvage bypass grafting in the areas of graft length, hemodynamics and tissue environment. More significantly, the graft healing pattern observed with this model is similar to what is seen in humans. Therefore, this experimental model provides a challenging and critical site for dynamic healing studies and comparisons of different types of vascular prostheses.