Arterial Implants Research Articles

The influence of age on the biological response to biodegradable zinc arterial implants

Medical devices to treat arterial diseases of older humans are routinely designed and developed using young animals. This is the case despite the significant declines of tissue regeneration, cell proliferation, and inflammation in aged humans that are not reflected in young animals. The widespread use of age-mismatched animals is particularly a concern for the testing of interactive materials, such as biodegradable metals whose dynamic interfaces continuously impact local cell and tissue regenerative processes. In order to determine the importance and impact of age differences in biodegradable stent material biocompatibility, we implanted both inert (platinum) and biodegradable (zinc) metal wires into the arteries of 1 year old and 3-month-old rats for a period of 6 months and compared the biological responses. It was found that the older animals developed a significantly larger neointimal encapsulating tissue for zinc implants vs. a smaller tissue response for the platinum implants relative to the younger rats. The neointimas of older rats contained dramatically fewer macrophages for both implant metals. The presence of neointimal smooth muscle cells was also decreased in the older rats. Endothelial cell regeneration in the old arteries was not impacted by the different metal implants. These findings demonstrate that neointimal responses to metal implants in arterial tissue are strongly impacted by age-related changes. The findings also suggest that the reliance on young animal models to evaluate metal implants intended for the arteries of considerably older individuals may substantially over predict the biocompatibility.

Conventional Platinum Metal Implants Provoke Restenosis Responses in Atherogenic but Not Healthy Arteries

Platinum-containing stents are commonly used in humans with hypercholesterolemia, whereas preclinical stent evaluation has commonly been performed in healthy animal models, providing inadequate information about stent performance under hypercholesterolemic conditions. In this investigation, we used an ApoE−/− mouse model to test the impact of hypercholesterolemia on neointima formation on platinum-containing implants. We implanted 125 μm diameter platinum wires into the abdominal aortas of ApoE−/− and ApoE+/+ mice for 6 months, followed by histological and immunofluorescence examination of neointimal size and composition. It was found that ApoE−/− mice developed neointimas with four times larger area and ten times greater thickness than ApoE+/+ counterparts. Neointimas developed in the ApoE−/− mice also contained higher amounts of lipids quantified as having 370 times more coverage compared to ApoE+/+, a 3-fold increase in SMCs, and a 22-fold increase in macrophages. A confluent endothelium had regenerated in both mouse strains. The ApoE−/− mice experienced luminal reductions more closely resembling clinically relevant restenosis in humans. Overall, the response to platinum arterial implants was highly dependent upon the atherogenic environment.

Analysis of vascular inflammation against bioresorbable Zn-Ag based alloys.

Zinc (Zn) has emerged as a promising bioresorbable stent material due to its satisfactory corrosion behavior and excellent biocompatibility. However, for load bearing implant applications, alloying is required to boost its mechanical properties as pure Zn exhibits poor strength. Unfortunately, an increase in inflammation relative to pure Zn is a commonly observed side-effect of Zn alloys. Consequently, the development of a Zn-based alloy that can simultaneously feature improved mechanical properties and suppress inflammatory responses is a big challenge. Here, a bioresorbable, biocompatible Zn-Ag-based quinary alloy was comprehensively evaluated in vivo, in comparison to reference materials. The inflammatory and smooth muscle cellular response was characterized and correlated to metrics of neointimal growth. We found that implantation of the quinary alloy was associated with significantly improved inflammatory activities relative to the reference materials. Additionally, we found that inflammation, but not smooth muscle cell hyperplasia, significantly correlates to neointimal growth for Zn alloys. The results suggest that inflammation is the main driver of neointimal growth for Zn-based alloys and that the quinary Zn-Ag-Mn-Zr-Cu alloy may impart inflammation-resistance properties to arterial implants.

Zn2+-dependent suppression of vascular smooth muscle intimal hyperplasia from biodegradable zinc implants.

Biodegradable arterial implants based on zinc have been found to suppress neointimal hyperplasia, suggesting that biodegradable materials containing zinc may be used to construct vascular implants with a reduced rate of restenosis. However, the molecular mechanism has remained unclear. In this report, we show that zinc-containing materials can be used to prevent neointimal formation when implanted into the rat aorta. Indeed, neointimal cells were significantly more TUNEL positive and alpha-actin negative at the interface of biodegradable zinc vs. biostable platinum implants, in association with greater caspase-3 activity. Although zinc stimulated extensive neointimal smooth muscle cell (SMC) death, macrophage and proinflammatory markers CD68 and iNOS were not increased in neointimal tissue relative to biostable platinum control implants. Using arterial explants, ionic zinc was confirmed to promote SMC apoptosis by activating the caspase apoptotic signaling pathway. These observations suggest that zinc-containing materials can be used to construct vascular implants such as stents with reduced neointimal hyperplasia.

Модель животного для доклинического изучения артериальных имплантов

Модель животного для доклинического изучения артериальных имплантов

Infected Abdominal Aortic Grafts

Aortic grafts were inserted in 1711 patients at Ottawa Civic Hospital (OCH) between 1976 and 1986. Aorto-iliac occlusive disease was the indication in 884 while in 827, the graft was inserted for abdominal aortic aneurysms. Graft infection occurred in 12 patients; six presenting with gastrointestinal bleeding due to aorto-enteric fistula (AEF) and the other six presenting with groin abscesses, mostly as a draining sinus. These were treated with graft excision and immediate extra-anatomic bypass. Seven patients died, giving a mortality rate of 58%. Three surviving patients required above-knee amputation. These results are comparable to the results of others in the literature; therefore, continuing assessment of all aspects of graft infection and the search for more effective methods of prevention and management are needed.

Noninvasive measurements of nonlinear arterial elasticity.

To describe fully the compliance characteristics of an artery with nonlinear elastic properties, measurements must be obtained over a wide range of pressures. Furthermore, repeated measurements, as required in temporal studies of arterial implants, require that the measuring technique be noninvasive. The application of a pulsed ultrasound echo-tracking device is described, which fulfills both criteria. Nonlinear compliance-pressure (CP) curves were obtained from the femoral arteries of dogs, with the use of halothane anesthesia to vary systemic pressure, and were used to compare the gross elastic properties of different vessels. Studies using controlled hemorrhage or the vasoactive drugs, nitroprusside and levarterenol (norepinephrine), were used to verify that the CP curves obtained during halothane anesthesia did not reflect varying degrees of smooth muscle activation. However, surgical exposure did temporarily reduce arterial compliance at pressures between 60 and 140 mmHg. The effect of vasoactive intervention and of postsurgical changes in arterial or graft compliance can thus be quantitated by use of CP curves or by comparing incremental elastic moduli, which can also be estimated from the noninvasively derived measurements.

The problem of blocked aorto-coronary artery vein grafts: Report of three cases with successful treatment by intraventricular arterial implants and omental grafts

The problem of blocked aorto-coronary artery vein grafts: Report of three cases with successful treatment by intraventricular arterial implants and omental grafts

Myocardial Revascularization by Internal Thoracic Arterial Implants: Longterm Follow-up

A 100 percent follow-up report on 198 patients who underwent implantation of either a single internal thoracic artery (185 patients) or both arteries (13 patients) into the left ventricular myocardium up to ten and a half years after operation, is presented. Surgical (30-day) mortality was 8.5 percent. Implant arteriograms, performed in 89 percent of the survivors one year after operation, were graded according to the degree of opacification of the implant and the collateralized coronary artery.

Mortality From Ischemic Heart Disease

To the Editor.— Dr. Anderson's stimulating article on Mortality From Ischemic Heart Disease (224:336, 1973) saved me considerable work, for only a few weeks ago I had thought of reviewing available mortality data in order to confirm the suspicion detailed in the next paragraph. I believe that in 1920 the only treatments for ischemic heart disease in use that have survived to date are morphine, nitrites, epinephrine, quinidine, xanthines, mercurial diuretics, oxygen, digitalis, and phlebotomy. Then came the organic nitrates, pericardial poudrage, cervical sympathectomy, internal mammary artery ligations, digoxin, procainamide, cardiac catheterization, awareness of lipids and cholesterol and prudent diets, antismoking campaigns, pressor amines, antihypertensive drugs, intensive and then coronary care units, myocardial arterial implants, electroconversion, central venous pressure, cardiac pacing, propranolol, lidocaine, heart transplant, infarctectomy, and coronary bypass surgery. Despite these hailed advances, the mortality curve has escalated without a discernible ripple. This most discouraging and sobering observation serves

The nature of early runoff in myocardial arterial implants: A morphologic and hemodynamic reappraisal

The nature of early runoff in myocardial arterial implants: A morphologic and hemodynamic reappraisal

Results of aorta-coronary bypass graft surgery. Comparison with arterial implants and medical treatment

Results of aorta-coronary bypass graft surgery. Comparison with arterial implants and medical treatment

Surgical procedures for coronary artery disease.

Coronary atherosclerosis is a biochemical disease of uncertain etiology which produces myocardial ischemia from mechanical obstruction of the coronary arteries. Operative procedures are designed to improve the flow of blood to ischemic areas of myocardium, but, of course, do nothing to alter the underlying biochemical abnormality. Hopefully, dietary and other therapeutic procedures will be found to prevent progression of the process and bring about possible improvement in coronary atherosclerosis; however, significant data are not yet available. Hence, at present, operative proce­ dures which directly increase myocardial blood flow offer one of the best methods of therapy for patients seriously disabled with coronary disease . Since the introduction of bypass grafting for coronary artery obstruc­ tion in 1967-1968, scarcely four years ago, probably more experience and interest has accumulated with direct surgical procedures for coronary artery disease than in the entire span of time since Beck began his initial attempts to revascularize the heart between 1935 and 1940. Most discussion in this review will be concerned with bypass grafting, this procedure having become the mainstay of operative therapy for most patients. Arterial implants and excision of ventricular aneurysms or scars will be mentioned briefly.

Surgical procedures for coronary atherosclerosis

HE RAPID EVOLUTION of bypass grafting for coronary artery disease during the past 3 yr has greatly stimulated the development of new techniques for diagnosis and therapy.1-3 In this critique of the status of different surgical approaches, six different areas can be delineated: elective bypass grafting for angina pectoris; bypass grafting for congestive failure; left ventricular aneurysms, scars, and akinetic areas; preinfarction angina; arterial implants; and acute myocardial infarction-assisted circulation. E~~crrrvn BYPASS GRAFTING FOR ANGINA P~crom The pathologic basis for bypass grafting, discussed earlier in this symposium, is based on the fact that coronary atherosclerosis occurs principally in the proximal one-third to one-half of the major coronary arteries, with the distal vessels remaining patent in the majority of patients. When Green examined a series of nearly 50 hearts with atherosclerosis in the proximal left anterior descending coronary artery, the distal vessel was found to be patent in over 90X4 Similarly Berger recently described a postmortem study of 300 hearts with coronary atherosclerosis in which a patent segment was found distal to the area of obstruction in 80-90%; however, this finding varied with the pattern of proximal obstruction present5 Although this high frequency of patent distal vessels has long been noted by pathologists, its therapeutic significance was not appreciated because the arteries are small (1.0-2.5 mm internal diameter) and may appear even smaller when examined in contracted postmortem hearts. 5 An important point in surgical technique is that these collapsed vessels distal to an obstruction can often be gently dilated with small graduated probes to more than 50% of the initial diameter. A combination of fortunate circumstances led to the rather belated discovery of the widespread feasibility of bypass grafting. As recently as 1967, any direct operative procedure upon the left coronary artery was avoided because of a prohibitive mortality, exceeding 50%’ It is astonishing now, only 4 yr later, that bypass procedures can be regularly performed upon the left coronary artery with an operative risk of less than 5%. The most significant factors permitting this low mortality rate include the immediate increase in flow of blood to ischemic myocardium, the technical advances in microsurgery which permit effective anastomoses to arteries as small as 1.0 mm internal diameter, and the increasing safety of all operative procedures performed with cardiopulmonary bypass.

Evaluation of myocardial revascularization with arterial implants. An objective study using electrocardiography and maximal stress testing.

A study was made of 164 patients who had received systemic arterial implants for myocardial revascularization. This included 63 patients with a single Vineberg, 78 with a double Vineberg, and 23 in whom splenic artery implants had been performed with or without internal mammary artery implants. All had preoperative coronary arteriograms, and all but six had preoperative treadmill stress tests. Operative mortality was 6.7%. In 93 patients, all of whom had had positive stress tests preoperatively, comparison was made with postoperative stress tests 6 months to a year after operation. In 28% no ischemia could be demonstrated on maximal stress testing. In an additional 34.4% there was significant improvement. Postoperative angiography of the implants was obtained in 53 patients who had been studied by treadmill stress testing. The stress testing was found to be a more critical objective method of appraisal of functional improvement.

Direct blood flow studies of clinical internal thoracic (mammary) arterial implants.

Direct blood flow studies of clinical internal thoracic (mammary) arterial implants.

Prognosis in Severe Angina Pectoris with Medical Versus Surgical Therapy.

Meeting Abstracts1 May 1970Prognosis in Severe Angina Pectoris with Medical Versus Surgical Therapy.Henry I. Russek, M.D., F.A.C.P., Burton L. Zohman, M.D., F.A.C.P.Henry I. Russek, M.D., F.A.C.P.Search for more papers by this author, Burton L. Zohman, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-781_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe response of 100 patients with severe angina pectoris under long-term treatment with propranolol and isosorbide dinitrate has been determined by controlled objective evaluation and compared with the results obtained in 86 comparable patients treated surgically by means of double arterial implants. Both series were similar with regard to severity of angina, prevalence of previous myocardial infarction, and angiographic observations. A higher prevalence of seriously ill patients was present in the medically treated group. The dosage of propranolol was 20 to 100 mg, orally, t.i.d. before meals, and that of isosorbide dinitrate, 5 mg sublingually t.i.d. after meals. During 2... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 781-781KeywordsAnginaMyocardial infarction Issue Published: 1 May 1970 PDF DownloadLoading ...

Transfemoral internal thoracic (mammary) arteriography.

The use of arteriography in the evaluation of myocardial implants and coronary arteries is increasing. Transbrachial selective catheterization of the internal thoracic (mammary) artery (4), first described by Arner (1), has been used to evaluate internal thoracic arterial implants in the myocardium (2, 3). Ödman (6) demonstrated that percutaneous catheterization of the main branches of the aorta is feasible, and recently Judkins (5) reported this modification of Seldinger's technic (7) for transfemoral coronary arteriography. This paper presents a method of selectively catheterizing both internal thoracic arteries and the coronary arteries at one examination, using the transfemoral Seldinger technic. This procedure was developed for a number of reasons: (a) the need for arteriographic evaluation of bilateral internal thoracic arterial implantation in the myocardium; (b) the difficulty in using the left brachial retrograde approach for left internal thoracic arteriography following arteriographic or local arterial complications; (c) the belief that evaluation of myocardial revascularization is incomplete without concomitant assessment of coronary arterial disease by coronary arteriography; and (d) the ease of performing coronary arteriography by the Judkins technic, in contrast to the Sones technic (8) of selective coronary arteriography from the left brachial artery. Materials Fifty consecutive patients with internal thoracic arterial implantations in the myocardium were studied one to five years after the revascularization procedure. In 49, the implantation was single on the left side; in 1, it was double. The catheters and technic of coronary arteriography employed were essentially those utilized by Judkins (5) and Takaro (9). The right Judkins coronary catheter was used in three-fourths of the internal thoracic procedures, and a modified arteriographic catheter2 in one-fourth (Fig. 1). The modified internal thoracic catheter is a 100-cm-long No. 7 French Ducor Catheter3 which accommodates a wire 0.035 inch in diameter. The curves are similar to those of the right Judkins catheter, with the exception of the distal angulation. The internal thoracic catheter has two angulations, which are 60° at 0.5 cm from the tip and 30° at 2 cm from the tip. These angulations and the smaller catheter size allow the catheter to be manipulated somewhat more easily in the subclavian arteries. Method At catheterization, with the patient in the supine position on the x-ray table, a guide wire was inserted through a No. 18 thin-walled needle into the femoral artery and then into the abdominal aorta. A No. 7 Gensini Teflon catheter was used to dilate the puncture site in the femoral artery, after which the right Judkins catheter was inserted over the wire. The left internal thoracic artery was first catheterized by placing the catheter in a neutral position in the aortic arch as shown in Figure 2, A.

A critique of implantation of a systemic artery for myocardial revascularization

The extensive experimental data available indicate that about 90 per cent of arterial implants remain patent. The development of collateral circulation is an event which should be analyzed separately from continued patency, for collateral circulation is principally influenced by the degree of regional myocardial ischemia. With extensive collateral circulation, flow rates in the internal mammary artery may increase from 3 to 5 ml./min. following implantation to 30 to 40 ml./min. six months later. Reported clinical studies of over 1,000 operations from different groups indicate an operative mortality between 2 and 5 per cent, with a subsequent late mortality of 5 to 10 per cent in the first two years after operation. Eighty-five to 90 per cent of implanted vessels are subsequently found patent on angiography. Improvement of varying degree in angina pectoris can be anticipated in 60 to 75 per cent of patients. Postoperative angiography of the implanted vessel is the best method available for evaluating the efficacy of an implantation procedure, determining patency, degree of collateral circulation, and establishment of anastomoses with the regional coronary circulation. An arterial implant selectively perfuses only the regional coronary arteries near the implant. Hence, with diffuse coronary artery disease, multiple implants are necessary. A variety of techniques are being evaluated to revascularize the posterior portion of the left ventricle, including an autogenous vein graft, the gastroepiploic artery, a double internal mammary implant, and the splenic artery. 2,4,9,10,23,27–33,35–38 Most experience has been with the double internal mammary implant, which on postoperative study has been found to have patency rates near 90 per cent. Hopefully, in the future, methods for determining the rate of blood flow through the implant will become available, providing a numerical index of efficacy of revascularization. With such a guide, the influence of revascularization upon the risk of subsequent myocardial infarction and longevity can be evaluated. The data thus far available indicate that an implanted internal mammary artery does subsequently behave like a coronary artery and truly revascularize the heart. If such an achievement can be routinely accomplished at operation, a significant beneficial influence on the course of coronary occlusive disease can be anticipated. With the widespread prevalence of coronary artery disease, the consequences are far-reaching, for arterial implantations could soon become more widely needed than all other cardiovascular operations now currently performed.

Internal-mammary implantation operations for relief of myocardial ischemia.

A SATISFACTORY operation for myocardial ischemia has been slow of development because of the difficulty of evaluating results. Subjective improvement has been known to occur even when the operations were anatomically unsuccessful,1 and methods of measuring coronary blood flow sufficiently sensitive to detect small changes have not been perfected.Until recently there has been no method that has been reliable even for the detection of the anatomic patency of new channels in vivo. With the work of Sones and Shirey,2 however, permitting direct injection of contrast substance into small arteries, the patency of single arterial implants can now be visualized. This . . .