The intima of human coronary arteries

Intimal thickness relative to that of the media (r) was measured in coronary and internal mammary arteries from 300 human subjects. Whereas this ratio remained low (less than 0.17) in the mammary arteries, coronary arteries showed progressive intimal thickening (r = 4.10 by 60 years). The intimal surfaces of 70 pairs of arteries were compared by light, transmission, and scanning electron microscopy. The mammary arteries had a continuous endothelial lining, but the coronary arteries showed incomplete coverage of the thickened intima. In affected vessels the endothelial cells showed loss of attachment to adjacent cells and to the underlying tissue. It was concluded that the progressive intimal thickening of the human coronary artery, which develops early in life and is associated with defects in the internal elastic lamina, is also associated with endothelial cell separation and detachment, with the formation of denuded areas on the intimal surface.     

An update on internal mammary artery grafting for coronary artery disease

PURPOSE OF REVIEW: To describe recent results regarding the use of the internal mammary artery for coronary artery bypass grafting with emphasis on bilateral internal mammary artery grafting, patency, resistance to atherosclerosis, skeletonisation, composite arterial grafts, flow measurement, vasodilatation, and non-invasive imaging techniques. RECENT FINDINGS: Coronary artery bypass grafting plays an important part in coronary revascularisation and seems to be associated with a survival benefit in comparison with percutaneous coronary intervention. After 10 years, internal mammary arteries demonstrate better patency than vein grafts except when grafting moderately stenosed right coronary arteries. Bilateral internal mammary artery grafting increases survival further, but carries a higher risk of sternal complications. Skeletonisation may reduce this risk. The internal mammary arteries are used increasingly as composite arterial grafts and this technical solution should no longer be considered experimental. Perioperative flow measurement by the transit-time method is recommended while postoperative echocardiography represents an accurate method for evaluation of flow in internal mammary artery grafts. Multi-detector computed tomography allows for accurate assessment of all types of bypass conduits and native coronary arteries. At present, magnetic resonance imaging of internal mammary artery patency and flow is possible. SUMMARY: Newer studies confirm earlier data with respect to improved long-term survival when using internal mammary artery grafting, and this survival benefit is superior to percutaneous coronary intervention treatment. Bilateral internal mammary artery grafting improves survival further. Skeletonisation of the internal mammary artery provides extra length of grafts for complete arterial revascularisation. Non-invasive imaging techniques are increasingly sophisticated and may change the referral pattern for patients with coronary artery disease to either percutaneous coronary intervention or coronary artery bypass grafting.     

Myocardial revascularization using both internal mammary arteries. Clinical results and surgical strategy

To improve the benefits from coronary artery grafting with internal mammary artery (IMA) several technical manoeuvres and methods have been developed to increase the number of coronary arteries and their branches that can be bypassed with internal mammary arteries. Between November 1985 and December 1986, 50 patients underwent a surgical myocardial revascularization procedure using both internal mammary arteries by single or sequential anastomoses and supplemental saphenous vein graft. In 42% of these patients complete revascularization was achieved employing only internal mammary artery grafts. One hundred and twenty-six internal mammary artery grafts (77% of the total coronary bypass performed), were placed. One patient developed perioperative myocardial infarction. Reparative surgery to control immediate post-operative bleeding was required in two patients. Post-operative coronary angiography performed in 30 patients showed all patent internal mammary artery grafts but one. No late deaths occurred. Mean follow-up of 10 months was complete in 50 patients, of whom 94% are symptom free. We conclude that bilateral internal mammary artery grafting can be performed with low operative risk and can provide excellent long-term functional improvement and survival employing only high patency arterial conduit. Moreover, it doesn't significantly increase surgical morbidity.     

Characterization of the atherosclerotic plaque in the internal mammary artery

The current study examines, at both structural and ultrastructural levels, representative segments of internal mammary arteries obtained from 15 male patients, ranging in age from 45 to 75 years, with signs or symptoms of coronary heart disease. These segments were obtained at the time of coronary bypass surgery. Of the 15 segments examined, only 2 were found to have atherosclerotic plaques. In other segments, only an intimal thickening similar to that observed during aging was found. There was evidence of endothelial cell loss and defects of internal elastic lamina in the present study; however, there was no evidence of lipid accumulation in the intimal region. This observation agrees with previous findings that indicate that lipid accumulation is not a necessary factor for the formation of atherosclerotic plaques. During the study microfilament bundles, the so-called “stress fibers,” were also observed in the cytoplasm of the luminal side of endothelial cells. Stress fibers are known to be present in some endothelial cells in some pathologies such as regeneration after injury or hypertension. One of the features of the atherosclerotic plaques from an internal mammary artery was the presence of cells with contractile and synthetic phenotypes (contractile and synthetic smooth muscle cells), as well as cells with intermediate features. Cells with similar characteristics have also been observed during the development of the early stages of atherosclerosis, during embryological development of vessels, after experimental excimer laser treatment, and in primary cell culture. To our knowledge, this is the first report showing the ultrastructural features of the atherosclerotic plaques in the internal mammary artery. Cathet. Cardiovasc. Diagn. 43:413–420, 1998. © 1998 Wiley-Liss, Inc.     

Changes of coronary artery morphology and distribution of smooth muscle cells during progression of coronary atherosclerosis after heart transplantation

To examine the changes in coronary artery morphology and the distribution of smooth muscle cells during the progression of coronary atherosclerosis after cardiac transplantation, intimal and medial tissues were evaluated and the density of smooth muscle cells in the media were measured 30 and 60 days after transplantation by microspectrophotometry from rats receiving both auto- and allo-transplantation. Transplanted animals were given cyclosporine A to prevent graft rejection. Signs of rejection were not seen in the animals receiving auto-transplants. Rejection gradually progressed after transplantation in animals receiving allografts. The intima of the coronary arteries in the allograft group was significantly thickened at both 30 and 60 days after transplantation. The total intimal area in the day 60 group was significantly increased relative to the day 30 group among animals receiving allo-transplantation. The medial area of the coronary arteries in the group receiving allotransplantation was significantly less than that of the auto-transplantation group at both 30 and 60 days after transplantation. Azocarmine G stain revealed that the principal component of the thickened intima was smooth muscle cells. Coronary arteries in the allotransplantation group had disruption of the internal elastic lamina. We therefore hypothesized that the smooth muscle cells (SMCs) in the intima are probably derived from the media. The density of SMCs in the media was measured by microspectrophotometry. The density of SMCs was significantly decreased in the allo-transplantation group relative to the autotransplantation group. We conclude that intimal thickening of the coronary arteries is due to SMC proliferation, the myocytes being from the media through disruption of the internal elastic lamina. This process is similar to the mechanism of the development of atherosclerosis.     

Clinical value of morphological analysis of radial and internal mammary arteries in patients with ischemic heart disease

Morphological study of intraoperative biopsies of radial and internal mammary arteries taken from patients with ischemic heart disease during coronary bypass surgery revealed structural alterations of intima and media mostly in radial artery. These alterations depended on severity of arterial hypertension, presence of diabetes and extent of atherosclerosis. Hyperplasia of intima could be a basis for radial artery spasm and cause of graft stenoses and occlusions. Therefore protocols of pre and post operative care should take into consideration individual risk factors and morphological and functional features of an artery used for grafting.     

Inadequate flow after internal mammary-coronary artery anastomoses

The use of the internal mammary artery for revascularization of the coronary arteries has expanded over the last years. In a series of 250 consecutive coronary artery revascularizations, there was at least 1 internal mammary-coronary artery anastomosis in 222 patients (89%) and multiple internal mammary-coronary artery anastomoses were performed in 77 patients (31%). During the revascularization procedure, weaning from cardiopulmonary bypass was not possible in 4 patients with internal mammary-coronary artery anastomoses. These 4 patients showed signs of left ventricular failure, and additional saphenous vein bypass to the left anterior descending coronary artery, already revascularized by the left internal mammary artery, was performed. Weaning from cardiopulmonary bypass was then possible in 3 out of 4 patients. Thus, in some patients (1.2%), internal mammary-coronary artery anastomoses provide inadequate nutritional support for the myocardium.     

A further word of caution before using the internal mammary artery for coronary revascularization in patients with severe peripheral vascular disease!

Objectives: To characterize the clinical and angiographic characteristics of patients with collateralization from the internal mammary artery to the iliac artery. Background: The use of the internal mammary arteries for coronary revascularization has become the standard of care in coronary artery bypass grafting (CABG). However, in patients with aortoiliac disease, the internal mammary arteries may become a major collateral route to the lower extremities. Methods: A case series of 15 patients admitted for diagnostic coronary angiography were retrospectively identified, who were observed to have collateral flow from one or both internal mammary artery(ies) to an occluded or stenotic iliac artery. Results: The mean age was 63.2 ± 11.2 years; eight were men (53.3%). Coronary angiography was done as a perioperative evaluation for peripheral vascular surgery in three patients (20%) and was done because of cardiac symptoms or a positive thallium scan in 12 (80%). The finding that the mammary artery collateralized the iliac artery led to major treatment changes in all patients, seven (46.6%) who required CABG. In five patients (33%), use of one or both internal mammary artery(ies) for coronary grafts was avoided. CABG was deferred in one patient, whereas in another, percutaneous intervention in both iliac arteries preceded CABG using both mammary arteries. There was no incidence of postoperative acute lower extremity ischemia. Conclusions: Selective angiographic visualization of the internal mammary artery is an essential part of the preoperative evaluation in patients with severe peripheral vascular disease undergoing CABG. © 2009 Wiley‐Liss, Inc.     

Validation of an automated technique for determining the mechanical characteristics of coronary arteries during balloon angioplasty: laboratory assessment with necropsy segments

OBJECTIVES: To develop a technique for automatic inflation of a percutaneous transluminal coronary angioplasty (PTCA) balloon, with continuous measurement of the balloon pressure and volume; to validate the technique for determining the mechanical characteristics of coronary arteries. METHODS: During necropsy examination of the hearts of nine patients, 17 coronary artery samples were obtained for histological examination. A PTCA balloon was inserted into each artery, and the balloon pressure and volume were measured continuously during four repeat automatic inflations of the balloon. RESULTS: Of the 17 arteries, eight showed elastic, six plastic, and three fracture pressure-volume deformation characteristics. For the plastic deformations, the first inflation required a higher pressure than subsequent repeat inflations of 82 (61) kPa (mean (SD), range 25 to 175 kPa). For the three in the fracture group, the pressure drop because of the fracture occurred between 210 and 540 kPa. Two of these three showed a tear on visual inspection, and the other showed disruption of the intimal plaque on blinded histological examination. Of the six with plastic deformation characteristics alone, one showed a tear, and on histological examination two others showed splitting of the internal and external elastic lamina and one showed separation of intima and media. None in the elastic group showed any of these characteristics. CONCLUSIONS: Plastic and fracture deformation characteristics could be differentiated from elastic characteristics. Visual or histological evidence of fracturing was present in all three arteries identified during angioplasty as having pressure-volume fracture characteristics.     

Coronary artery bypass with 2 internal mammary arteries. Early clinical and angiographic results in 100 patients]

One hundred patients underwent coronary revascularisation with both internal mammary arteries between 1987 and 1990. The average age of the patients was 55 years. The left internal mammary was used in 97 of the 100 cases as a pediculated graft to revascularise the left anterior descending (66 cases), left lateral (27 cases) or a bissecting artery (4 cases). The right internal mammary was used as a pediculated graft in 51 cases and as a free graft to revascularise a left lateral (51 cases), left anterior descending (29 cases) or right coronary artery (20 cases). There was one death in the first 30 postoperative days. Morbidity was low with no cases of sternal infection. The average postoperative bleeding was 633 +/- 550 ml per patient. The incidence of phrenic nerve paralysis decreased from 36% in the first 50 patients to 6% in the second 50 patients. Angiography at the 10th postoperative day showed 4 occlusions out of 132 internal mammary arteries opacified (97% patency). Ninety four patients are asymptomatic and have negative exercise stress tests. Mortality and morbidity of coronary surgery using the two internal mammary arteries are therefore the same as those of conventional coronary surgery using saphenous veinar only one internal mammary artery, providing that it is reserved for patients in good general condition, under 65 years of age, without obesity or diabetes. This technique of coronary artery revascularization should provide better long-term results because of the high patency rate of the grafts.     

Percutaneous transluminal angioplasty involving internal mammary artery bypass grafts: a femoral approach

Percutaneous transluminal coronary angioplasty is an effective technique for the treatment of selected patients with ischemic heart disease due to coronary artery stenosis. Successful angioplasty in saphenous vein bypass grafts has been documented, but little experience has been reported using angioplasty in internal mammary artery to coronary artery bypass grafts. Nine of ten patients with stenosis in the internal mammary artery to coronary artery anastomosis or in the coronary vessel distal to the anastomosis site were successfully treated with angioplasty. One patient developed restenosis 1 month after the procedure, and a repeat angioplasty was successful. In one patient, the balloon catheter could not be advanced through the left internal mammary artery to the stenosis site. Technical features of internal mammary artery angioplasty are discussed, including the use of specially designed guiding wires, guiding catheters, and balloon catheters that facilitate angioplasty involving internal mammary arteries from the femoral approach.     

A comparison of coronary and internal mammary arteries and implications of the results in the etiology of arteriosclerosis

Comparison was made between the intimal thickening of the anterior descending branch of the left coronary artery and the internal mammary artery in 352 necropsy examinations. The coronary arteries showed severe intimal thickening, progressing in severity throughout life, whereas the internal mammary showed no more than slight changes at any age. These observations, together with the variation in severity of the changes in different portions of the same vessel, and the freedom from this disease of the smaller arteries throughout the body, strongly suggest that a local or anatomic factor is the dominant influence in coronary artery disease.     

Late patency of recycled internal mammary artery: verification by Doppler echocardiography and coronary angiography

We report the case of a 57-year-old man who had presented with exertional angina early in 1997 and had subsequently undergone myocardial revascularization with the use of both internal mammary arteries. Two months after surgery, the patient was readmitted to the hospital with unstable angina. Coronary angiography revealed a 90% occlusion of the left internal mammary artery anastomosis, which was attached to the left anterior descending coronary artery. At reoperation, the left internal mammary artery was detached from the left anterior descending coronary artery, probed and injected with papaverine, checked for patency, and regrafted to the same coronary artery. Recycling of the left internal mammary artery was facilitated by the harvesting and routing technique that had been used during the previous operation. At the patient's 1-year follow-up visit, both Doppler echocardiography and coronary angiography showed patency of the recycled graft. We conclude that recycling of the left internal mammary artery is a safe and effective option in selected patients who require reoperation after myocardial revascularization.     

Diffusion of gamma globulin into the arterial wall identifies localized entry of lipid and cells in atherosclerosis

BACKGROUND: The localization of atheromatous lesions in vulnerable arteries and their relatively rare occurrence in other arteries of the same subject cannot be explained by current theories of the aetiology of atherosclerosis. OBJECTIVE: To determine whether abnormal diffusion of gamma globulin into the arterial wall from the lumen will identify defects of barrier function allowing localized entry of lipid and cells in atherosclerosis. METHODS: Paraffin sections of left anterior descending coronary arteries and corresponding internal thoracic arteries from 80 human subjects aged 1-65 years were stained for gamma globulin by the immunoperoxidase technique. Duplicate sections were stained with orcein to demonstrate the elastin structure. RESULTS: The barrier function of the luminal surface of the thickened intima was associated with the presence of an elastin lamina beneath the endothelial cells. With advancing age, the coronary arteries exhibited breakdown of this barrier function in localized areas with entry into the arterial wall of gamma globulin, lipid and cells. This was rare in the internal thoracic artery. CONCLUSION: Lack of continuity or incomplete formation of this sub-endothelial lamina, which was seen particularly in the coronary artery, was associated with localized entry into the arterial wall of gamma globulin, lipid and cells from the circulating blood and with the development of atheromatous lesions.     

In vitro high resolution intravascular imaging in muscular and elastic arteries.

High resolution (125-microns lateral, 55-microns axial) images of 16 muscular (femoral) and 15 elastic (common carotid) human arteries were made in vitro with use of a prototype 45-MHz intravascular imaging system. Four distinct regions of scattering, excluding plaque, were identified in the ultrasound images corresponding histologically to the adventitia, media, thickened intima and elastic laminae, both internal and external. Arterial samples imaged under pressure and in a collapsed state underwent dimensional changes but exhibited similar levels of backscatter amplitude. All the elastic arteries displayed a prominent echogenic media, whereas all the muscular arteries displayed an echolucent media. Scattering from the internal elastic lamina in muscular arteries provided an excellent landmark for defining the location and extent of intimal thickening or plaque. In elastic arteries the internal elastic lamina could not be distinguished from the echogenic media; consequently, the boundary between the media and intimal layer was indistinct. Differences in the relative concentration and organization of collagen and elastin were found to provide a consistent explanation for the differences in scattering that were observed between individual layers within an artery as well as between muscular and elastic arteries.     

The internal elastic lamina in normal and abnormal human arteries. A barrier to the diffusion of macromolecules from the lumen

The distribution of albumin in the walls of normal and abnormal human arteries from surgical and autopsy material was studied to gain insight into the barriers affecting the outward diffusion of plasma macromolecules. In normal arteries there was a steep reduction in albumin concentration at the position of the internal elastic lamina (IEL), suggesting that it acts as a barrier to diffusion. In abnormal arteries such as small vessels present in inflammatory tissue, the IEL was frequently discontinuous and associated with intimal thickening. In these small vessels reduplication of the IEL at the luminal margin of the thickened intima appeared to offer an effective new barrier to the diffusion of albumin from the lumen. In larger vessels such as the coronary arteries of adults, which invariably showed discontinuities of the IEL and intimal thickening, no such effective reduplicated IEL was present, and albumin diffused freely into the thickened intima. These observations suggest that the failure to form and maintain an IEL surrounding the arterial lumen may be associated with continued proliferation of intimal cells and progressive intimal thickening.     

Combined two-dimensional and Doppler echographic examination of internal mammary artery grafts from the supraclavicular fossa.

The noninvasive examination of internal mammary artery grafts is gaining importance with the increasing use of this vessel in the surgical treatment of coronary atherosclerosis of the left anterior descending artery. We studied 36 patients (37 internal mammary artery grafts) with combined two-dimensional and pulsed Doppler echography from the supraclavicular fossa. Adequate visualization and Doppler signals were obtained in 95% of arterial grafts. Twenty-four grafts leading to an area without evidence of old myocardial infarction or ischemia and 10 grafts leading to an area of old myocardial infarction but without evidence of ischemia on exercise showed a significant decrease of the peak systolic velocity and of the peak systolic velocity/peak diastolic velocity ratio as compared to the controls, which consisted of the contralateral internal mammary arteries in situ. One patient with a distally subtotally occluded mammary artery graft had a flow pattern different from the other bypassed mammary arteries. It seems that combined two-dimensional and pulsed Doppler echography is a useful method to evaluate the functional status of internal mammary artery grafts.     

Evaluation of internal mammary artery implantation

Twenty patients who underwent internal mammary artery implantation for the treatment of incapacitating angina pectoris were studied before and 1 year after operation. Studies included treadmill exercise test, right heart catheterization at rest and during exercise, selective coronary adenography and selective visualization of the implanted arteries. Operative mortality was 8.5 percent. Postoperatively, only 1 patient showed improvement in the treadmill exercise stress test. Thirteen of 18 patients demonstrated a deterioration in hemodynamic performance. Angiographic studies revealed only 3 patients having collateral vessels large enough to fill a major coronary artery. These data confirm the lack of objective evidence of benefit following internal mammary artery implantation; the frequent deterioration of myocardial performance seen may be related to the operative procedure.     

Hyperplasia of coronary intima in young males in relation to development of coronary heart disease in adults

The aim of the investigation was to study structural features of coronary arteries in young males which may influence the development of stenosing coronary atherosclerosis in older age. We studied the coronary arteries from 84 males, 10-39 years old, who died from accidents in Moscow, Malmo and Riga, and 98 males aged 40 and above from Moscow who died from coronary heart disease (71 cases) or other diseases (27 cases). In children and young males from all three cities, musculo-elastic hyperplasia of the coronary intima took place constantly but with different degrees of expression; a strict relationship of the intimal thickness and age was observed. Histometric investigations of the right coronary artery showed that in young males of Riga, in comparison with those of Malmo, the intima was significantly thicker both outside (69.6+/-2.8 and 58. 2+/-2.5 microm) and within the area of cushion like thickening (118. 8+/-4.0 and 101.9+/-3.8 microm), they had more extended cushion-like thickening of intima (42.6+/-3.0 and 30.8+/-3.3% to the length of the artery circumference) and destroyed parts of the internal elastic lamina (28.3+/-1.9 and 19.1+/-1.7% of its length). In males older than 40 years, severe coronary atherosclerosis and stenosis was also significantly more common in Riga than in Malmo. Our data indicate that with age the intimal musculo-elastic hyperplasia in the coronary arteries is transformed to a fibro-elastic layer. The thickness of this layer in the presence of stenosing plaques (>75% of arterial lumen) was much greater than in the presence of plaques with stenoses less than 50% (188.1+/- 7.3 and 69.8+/-4.5 microm, respectively). CONCLUSION: The development of stenosing coronary atherosclerosis is closely related to the degree of musculo-elastic intimal hyperplasia in childhood and young age. The formation of a fibro-elastic layer in the coronary intima decreases the ability of the artery to dilate during the development of atherosclerosis.     

The string phenomenon: an important cause of internal mammary artery graft failure

Internal mammary arteries are the grafts of choice for coronary artery bypass because they are generally free of atherosclerosis and they have high patency rates as grafts. There are, however, increasing reports of graft failure due to diffuse or distal narrowing, known as the string phenomenon. From June 1999 to October 1999, we prospectively reviewed all cases of internal mammary artery angiography at our institution. Twenty-eight cases of internal mammary artery graft failure were identified (M:F, 15:13; mean age, 62 years) out of 261 patients who had undergone internal mammary artery grafting at any institution, including ours. The mean interval between coronary artery bypass and re-angiography was 35 months. There was evidence of competitive flow in 81% (22 of 27) of patients whose internal mammary grafts had developed the string sign. This observational study supports the hypothesis that competitive flow predisposes internal mammary grafts to the string phenomenon. Given the high frequency of competitive flow situations amongst patients with internal mammary artery graft failure, caution should be exercised in the anastomosis of the internal mammary artery to recipient vessels that are less than severely stenosed.