Sections Of Coronary Arteries Research Articles

946-108 High Resolution Imaging of Human Arterial Walls Via Optical Coherence Tomography

Optical coherence tomography (OCT) is a recently developed technology which can perform micron scale, cross sectional tomographic imaging. OCT performs imaging using interferometric optical ranging of low coherence infrared light or ultrashort laser pulses which are backscattered from tissue. This technique is analogous to the reflected acoustical wave measurements of conventional B mode ultrasound. In this study, two dimensional cross sectional images were generated of in vitro human aorta and coronary artery sections obtained postmortem. The microstructure of normal and atherosclerotic tissue was displayed as a false color or grey scale image. The bandwidth of the photodiode source (1300 nm) allowed a resolution of 20 microns, almost 10 times greater than conventional intravascular ultrasound. Different morphologies including fatty, fibrous, and water based tissue, were well differentiated in the images and corresponded to histologic sections. Imaging was possible with up to 1 mm penetration into the tissue with little attenuation from heavy calcification. The typical image acquisition time was in the range of 2–3 seconds. A more detailed analysis of the optical properties of relatively uniform, structurally distinct tissues, such as adipose, skeletal muscle, and tendon, was performed to further confirm the contrast between fat, muscle, and connective tissue. The contrast ratios of muscle, tendon, and fat, were measured to be 1:78:22, respectively. The effective refractive indices and optical penetration depths in different tissue types were also measured. OCT is a promising new technology for high resolution “optical biopsy”. It does not require direct contact with the vessel wall and could be performed via a catheter integrated with a relatively inexpensive fiberoptic bundle. Future studies utilizing currently available femtosecond lasers are expected to both increase the resolution of OCT, which is dependent on bandwidth or pulse duration. to ≈3–4 microns and allow visualization of structures deeper into tissues.

Localization of calcium channels of the L-type in human epicardial arteries: a light microscope autoradiographic study.

The anatomical localization of Ca2+ channels of the L-type was analyzed in sections of the human right and anterior interventricular coronary arteries by using in vitro light microscope autoradiography associated with radioligand binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronary arteries was time-, temperature- and concentration-dependent. Analysis of binding isotherms revealed a dissociation constant value of about 0.5 nM in the two arteries and maximum binding capacities of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5 for the anterior interventricular branch. The pharmacological profile of [3H]nicardipine binding to sections of human coronary arteries was consistent with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkylamines, benzothiazepine or non-selective channel modulators were weak competitors or ineffective. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cells. A lower accumulation of the radioligand occurred in the tunica adventitia, whereas no specific binding was found in the tunica intima. Study of the localization of Ca2+ channels in sections of human coronary arteries may contribute to a better understanding of the mechanism of the marked coronary dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro preparations and in vivo.

Endothelin-Like Immunoreactivity in Atherosclerotic Human Coronary Arteries

Endothelin-1 (ET-1) is an endothelium-derived peptide with powerful vasoconstrictor and mitogenic properties. A pathophysiologic role for ET-1 has been suggested, because increased plasma and tissue levels of this peptide have been described in a number of disease states, including atherosclerosis. Immunocytochemistry was carried out on sections of coronary arteries from patients undergoing cardiac transplantation to identify regions exhibiting ET-1-like immunoreactivity (ET-LI). ET-LI was associated with endothelial cells of the lumen and with microvascular endothelial cells of the adventitia, regions of neovascularization, and recanalization within atherosclerotic plaques. ET-LI was observed in the tunica media, and patches of immunostaining were also associated with smooth-muscle cells within the plaque. These results indicate that ET-1 not only is released from the vascular endothelium but, under certain conditions, is also generated by smooth muscle cells. An autocrine action of ET-1 is well established, and our results suggest that this peptide is involved in neovascularization and smooth-muscle cell proliferation associated with atherosclerosis.

3H]Bosentan Binding to Human Coronary Artery

The binding characteristics and localization of bosentan, an orally active endothelin-1 (ET-1) antagonist, were studied on sections of human coronary artery by in vitro autoradiography. Competition studies were performed to determine the ability of bosentan to prevent [125I]ET-1 binding to the coronary vasculature. The effects of bosentan on ET-1-induced contraction of the coronary artery were also studied in vitro. [3H]Bosentan bound to the tunica media of the human coronary artery. Unlabeled bosentan prevented [125I]ET-1 binding to this vessel in a concentration-dependent manner, and functional studies indicated that bosentan antagonizes ET-1--induced constriction. These data show that bosentan is able to reduce ET-1 binding to the human coronary artery and ET-1 constrictor effects in vitro. Bosentan is an orally active ET-1 antagonist, and these results suggest that this compound might be used to block the effects of locally released ET-1 in pathologic conditions, such as atherosclerosis, angina, and myocardial ischemia.

Distribution of Endothelin Receptors in Atherosclerotic Human Coronary Arteries

Summary: It has been suggested that the potent vasoconstrictor and proliferative agent endothelin (ET) may contribute to the development and effects of atherosclerosis. The aim of this study was to use autoradiography to examine the distribution of ET receptors in human coronary artery with a range of pre-atherosclerotic and atherosclerotic lesions. ET-1 receptors in epicardial coronary artery sections were visualized according to the binding of [125I]ET-1 (100 pM), the ETA-selective radioligand [125I]PD151242 (100 pM), and the ETB-selective [I25I]BQ3020 (300 pM). Dense [125I]ET-1 binding was demonstrated in the smooth muscle of the media of all arteries studied and ETA receptors, defined by [125I]PD151242 binding, predominated. Intense [125I]BQ3020 binding to ETB receptors was apparent on perivascular structures, such as adventitial lymphatics. In contrast, ET receptors were absent in neointimal smooth muscle. In regions of recanalized organized thrombus, microautoradiography revealed ETA receptors on the smooth muscle of new vessels. Discrete clusters of ETB receptors were detected in sections through the atherosclerotic arterial wall. A similar pattern of staining for von Willebrand factor was seen in adjacent sections. This suggests that ETB receptors are present on endothelial cells of neovascularization, penetrating the diseased media.

Distribution of Endothelin Receptors in Atherosclerotic Human Coronary Arteries

It has been suggested that the potent vasoconstrictor and proliferative agent endothelin (ET) may contribute to the development and effects of atherosclerosis. The aim of this study was to use autoradiography to examine the distribution of ET receptors in human coronary artery with a range of pre-atherosclerotic and atherosclerotic lesions. ET-1 receptors in epicardial coronary artery sections were visualized according to the binding of [125I]ET-1 (100 pM), the ETA-selective radioligand [125I]PD151242 (100 pM), and the ETB-selective [125I]BQ3020 (300 pM). Dense [125I]ET-1 binding was demonstrated in the smooth muscle of the media of all arteries studied and ETA receptors, defined by [125I]PD151242 binding, predominated. Intense [125I]BQ3020 binding to ETB receptors was apparent on perivascular structures, such as adventitial lymphatics. In contrast, ET receptors were absent in neointimal smooth muscle. In regions of recanalized organized thrombus, microautoradiography revealed ETA receptors on the smooth muscle of new vessels. Discrete clusters of ETB receptors were detected in sections through the atherosclerotic arterial wall. A similar pattern of staining for von Willebrand factor was seen in adjacent sections. This suggests that ETB receptors are present on endothelial cells of neovascularization, penetrating the diseased media.

Electrophysiological studies of the interaction between ventricular myocardium and coronary artery in monkeys.

1. The electrical influence of the coronary arteries on ventricular muscle was investigated using strips of ventricle that included a section of coronary artery (cardiac preparation) and isolated coronary arteries dissected from the ventricle (arterial preparation). 2. In cardiac preparations, a hyperpolarizing response was recorded from the epicardial surface of the ventricular muscle when acetylcholine (ACh) was added to the organ bath, on condition that the internal diameter of the coronary artery was between 0.15 and 0.6 mm, that the vessel ran at a depth of 0.2 mm or less below the surface of the preparation, and that the recording microelectrode was immediately adjacent to the artery. 3. ACh-induced hyperpolarization was not detected in cardiac preparations which had no detectable arteries, or at sites distant from visible arteries. 4. In arterial preparations, a similar hyperpolarizing response was evoked by ACh in all vessels with an i.d. of 0.15-1.2 mm. 5. In a preparation combining ventricular muscle and a strip of coronary artery (with the vascular endothelium in direct contact with the epicardial surface of the ventricular myocardium), hyperpolarization was also observed from the ventricular muscle after application of ACh. 6. The hyperpolarizing response of the ventricular myocardium in the cardiac preparation and in combined preparations of ventricular muscle and coronary artery was weakened or abolished by removal of the arterial endothelium. 7. These results indicate that some substance released from the coronary arterial endothelium after stimulation by ACh induces hyperpolarization of the ventricular myocardium.

Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis.

Coronary atherosclerosis is frequently associated with calcification of arterial plaque. To understand the mechanisms responsible for the formation of atherosclerotic calcification, we examined human coronary arteries for the presence and extent of mineral. In sections stained specifically for mineral, staining was diffuse and present in all atherosclerotic plaques. Hydroxyapatite was not detected in normal coronary artery sections. Distribution of hydroxyapatite coincided with a similar distribution of calcium detected by a radiodense pattern using contact microradiography of the same sections before cytochemical staining. By energy-dispersive x-ray microanalysis, the chemical composition of calcified sites was identical to hydroxyapatite (Ca10[PO4]6[OH]2), the major inorganic component of bone. Osteopontin is a phosphorylated glycoprotein with known involvement in the formation and calcification of bone and is regulated by local cytokines. Human coronary artery segments (14 normal and 34 atherosclerotic) obtained at autopsy were evaluated immunohistochemically using polyclonal antibodies generated against human osteopontin. Immunohistochemistry for osteopontin indicated intense, highly specific staining in the outer margins of all diseased segments at each calcification front; staining was evident throughout the entire plaque. Conversely, arterial segments free of atheroma and calcification and sections treated with nonimmune serum had no evidence of positive staining. Osteopontin, a protein involved in mineralization is specifically associated with calcific coronary atheroma and may play an important role in the onset and progression of this disease in human coronary arteries. The deposition of noncollagenous proteins such as osteopontin may regulate the presence or absence of calcification and ultimately alter vessel compliance.

Interactions between calcium channel blockers and α‐adrenoceptors in the human coronary and mammary arteries: a radioligand binding study

The study was designed to assess whether Ca2+ channel blockers of the dihydropyridine family (felodipine, nicardipine, nifedipine, nimodipine, nitrendipine and nisoldipine), and of the phenylalkylamine family (verapamil) have any effect on alpha-adrenoceptor binding to sections of the human right coronary and mammary arteries, measured using [3H]-dihydroergocryptine (DHT) as a ligand. Increasing concentrations of nicardipine, verapamil and nitrendipine competed with [3H]-DHT binding to sections of the human coronary and mammary arteries. The other compounds tested were without effect. Among the competitors of [3H]-DHT binding, nicardipine was the most powerful, with a 50% inhibition (IC50) value of approximately 10 nM. The pharmacological profile of competition with [3H]-DHT binding by nicardipine, in the presence or in the absence of guanosine triphosphate and NaCl, is consistent with antagonist activity of the dihydropyridine derivative at the alpha-adrenoceptor. This property may account for the lower sympathetic stimulatory activity elicited by nicardipine, in comparison with other Ca2+ channel blockers used in cardiovascular therapy.

Increased platelet deposition on atherosclerotic coronary arteries.

A ruptured atherosclerotic plaque leads to exposure of deeper layers of the plaque to flowing blood and subsequently to thrombus formation. In contrast to the wealth of data on the occurrence of thrombi, little is known about the reasons why an atherosclerotic plaque is thrombogenic. One of the reasons is the relative inaccessibility of the atherosclerotic plaque. We have circumvented this problem by using 6-microns cryostat cross sections of human coronary arteries. These sections were mounted on coverslips that were exposed to flowing blood in a rectangular perfusion chamber. In normal-appearing arteries, platelet deposition was seen on the luminal side of the intima and on the adventitia. In atherosclerotic arteries, strongly increased platelet deposition was seen on the connective tissue of specific parts of the atherosclerotic plaque. The central lipid core of an advanced plaque was not reactive towards platelets. The results indicate that the atherosclerotic plaque by itself is more thrombogenic than the normal vessel wall. To study the cause of the increased thrombus formation on the atherosclerotic plaque, perfusion studies were combined with immunohistochemical studies. Immunohistochemical studies of adhesive proteins showed enrichment of collagen types I, III, V, and VI, vitronectin, fibronectin, fibrinogen/fibrin, and thrombospondin in the atherosclerotic plaque. Laminin and collagen type IV were not enriched. von Willebrand Factor (vWF) was not present in the plaque. The pattern of increased platelet deposition in serial cross sections corresponded best with areas in which collagen types I and III were enriched, but there were also areas in the plaque where both collagens were enriched but no increased reactivity was seen. Inhibition of platelet adhesion with a large range of antibodies or specific inhibitors showed that vWF from plasma and collagen types I and/or III in the plaque were involved. Fibronectin from plasma and fibronectin, fibrinogen, laminin, and thrombospondin in the vessel wall had no effect on platelet adhesion. We conclude that the increased thrombogenicity of atherosclerotic lesions is due to changes in quantity and nature of collagen types I and/or III.

Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation.

Platelet activating factor (PAF) is a phospholipid released upon stimulation by a variety of cells and has been implicated in several pathophysiological events such as asthma and inflammatory diseases. However, although the ability to aggregate platelets in vitro was the first biological activity ascribed to PAF, its role in contributing to the in vivo formation of arterial thrombi has not been thoroughly clarified. Intravascular platelet aggregation was initiated in two different animal models of arterial stenosis and endothelial injury. An external constrictor was positioned around rabbit carotid arteries and canine coronary arteries. After placement of the constrictor, a typical pattern of flow developed in the stenotic vessels. This pattern of flow, characterized by progressive reductions of carotid or coronary blood flow followed by spontaneous or induced restorations of flow (cyclic flow variations, CFVs), is related to recurrent platelet aggregation at the site of the stenosis followed by dislodgment of the thrombus. After observing CFVs for 30 minutes, BN52021 (up to 1.2 mg/kg), a potent and selective PAF antagonist, was given intravenously to rabbits (n = 12) and dogs (n = 10). BN52021 completely inhibited CFVs in 10 of 12 rabbits, whereas it was relatively ineffective in abolishing CFVs in dogs (only 2 of 10 animals inhibited). This different effect of BN52021 was not explained by too small a dose of the drug to achieve a complete blockade of PAF receptors in dogs, since ex vivo platelet aggregation was completely inhibited in both rabbits and dogs in response to exogenous PAF at concentrations up to 10(-5) mol/L. In a second group of 10 dogs, the hypothesis that PAF may become an important mediator of CFVs in dogs only several hours after endothelial injury was tested. After 30 minutes of baseline CFVs, these animals received a bolus of BN52021 up to 1.2 mg/kg. After this treatment, CFVs were completely abolished in 2 of 10 animals. The remaining 8 dogs were followed for an additional 8-hour period, at the end of which a second bolus of BN52021 was given. At this time, BN52021 was effective, as CFVs were abolished in 6 of 8 animals. These effects of BN52021 at 8 hours were not the consequence of a cumulative dose of the compound, since ex vivo platelet aggregation in response to PAF returned to baseline values immediately before administering the second dose. To identify possible sources of PAF other than aggregating platelets at the site of arterial stenosis, dogs in a third group were killed after 30 minutes (n = 7) and after 8 hours (n = 8) of CFVs. Histological sections of the stenotic coronary artery showed a marked leukocyte infiltration in these arterial segments after 8 hours of CFVs, whereas sections from dogs killed after 30 minutes showed only moderate or no infiltration. These data demonstrate that PAF plays an important role as a mediator of platelet aggregation in vivo in rabbits and dogs. In the canine model, PAF appears to become more important after leukocyte infiltration of the arterial wall, as it may contribute to initiating enough platelet activation to lead to cyclic flow variations at sites of arterial stenosis and endothelial injury. Data from the present study suggest that PAF antagonists may be used as antiplatelet agents.

Muscarinic cholinergic receptors in the human right coronary artery: a receptor binding and autoradiographic study

We used a combination of radioreceptor binding and autoradiographic techniques to study the pharmacological characteristics and anatomical localization of [3H]-quinuclidinyl benzilate (QNB) binding sites in the human right coronary artery. The ligand was bound to sections of the human right coronary artery in a manner consistent with the labelling of muscarinic receptors. The addition of pirenzepine or of carbachol to the incubation medium to generate displacement curves was indicative of the presence of M1 and M2 receptors in the right coronary artery. Autoradiography showed the localization of M1 sites primarily in the medial layer of the right coronary artery. M2 sites were located primarily in the adventitia. No [3H]-QNB binding sites were observed in the endothelium. A possible role of muscarinic receptors in the pathogenesis of coronary vasospasm is discussed.

Reconstructing the cross sections of coronary arteries from biplane angiograms

An algorithm that reconstructs the cross sections of the lumens of coronary arteries from two mutually orthogonal X-ray projections is described. The algorithm accommodates the possibility of elliptical, crescent, or star shapes. It represents each biplane projection of a transverse slice of the arterial lumen as a binary-valued image. The single-coordinate moments of these two projection images are equal to those of the slice. Since the cross-coordinate moments of the slice are not available from the projections, an algorithm to estimate these moments based on assumptions of smoothness and connectivity is developed. Once all the missing moments are estimated, the image of the slice can be estimated by inverting these moments, using the uniqueness theorem governing the relation between an image and its moments. Preliminary tests of the algorithm on synthetic data, on hardware phantoms and on a segment of a barium-enhanced in vitro coronary artery are reported.

Pathological and angiographic regression of coronary atherosclerosis by LDL-apheresis in a patient with familial hypercholesterolemia

We present the case of a 42-year-old male with familial hypercholesterolemia (FH) who had received long-term low-density lipoprotein (LDL)-apheresis before death occurred, presumably from an arrhythmia. He had been treated with double filtration plasmapheresis (DFPP) for 4 years and selective LDL adsorbent plasmapheresis (LAPP) for 2 years and 7 months. During the period of treatment (6 years and 7 months) he had received a total of 129 sessions of LDL-apheresis. Serum total cholesterol of the patient before the treatment was 638 mg/dl and during the treatment, the time-averaged values ranged from 336 mg/dl to 411 mg/dl for the first 4 years (with DFPP) and from 257 mg/dl to 364 mg/dl for the sequential 2 years and 7 months (with LAPP). Coronary angiograms were analysed for 13 segments of the coronary arteries using a digitized processing system. Analysis documented regression by identifying a reduction in percent stenosis from 34% to 20% in the proximal left circumflex artery (LCX), from 78% to 61% in the proximal right coronary artery (RCA), and from 92% to 72% in the middle RCA. In the other 10 segments analysed no significant regression and no progression were observed. The autopsy findings of the step-wise serial sections of the native coronary arteries did not record the formation of new and/or typical atheroma. In addition, a thickened intima, and an eccentric thickened wall lesion rich in collagen fiber were observed, although an accumulation of foam cells in the thickened wall lesions was found in some segments. This observation suggested scarring of the atheromatous plaque. We confirmed that LDL-apheresis performed over a period of 6 years and 7 months induced angiographic regression-,of coronary atherosclerosis in the patient with FH, and found that most of the atherosclerotic lesions were changed pathologically into sclerotic lesions rich in collagen fiber.

Electrical responses of coronary artery smooth muscle associated with the cardiac muscle action potential in the monkey.

1. In cardiac strips of the monkey ventricle which included a section of coronary artery (cardiac preparation), a depolarizing response, which appeared to be an excitatory junction potential (EJP), and a hyperpolarizing response were observed from the coronary artery smooth muscles when an action potential was generated in cardiac muscle by the application of electrical stimulation to the cardiac muscle alone. 2. In an isolated preparation of the coronary artery dissected from the ventricle (arterial preparation), similar responses, an EJP and a hyperpolarizing response, could be evoked by electrical stimulation. 3. In the cardiac preparation, the threshold of electrical stimulation for generation of the cardiac action potential and for production of an electrical response in the vascular smooth muscle were the same. 4. The EJP and the hyperpolarizing responses of the smooth muscle of the coronary artery ceased or were weakened by elimination of the adventitial connective tissues and endothelium, respectively, in both the cardiac preparation and the coronary artery preparation. 5. These results indicate that the action potential of cardiac muscle generated by electrical stimulation activates the nerves and the vascular endothelium, which, in turn, produce an EJP and a hyperpolarizing response of the coronary artery smooth muscle, respectively.

Compensatory enlargement of human atherosclerotic coronary arteries.

Whether human coronary arteries undergo compensatory enlargement in the presence of coronary disease has not been clarified. We studied histologic sections of the left main coronary artery in 136 hearts obtained at autopsy to determine whether atherosclerotic human coronary arteries enlarge in relation to plaque (lesion) area and to assess whether such enlargement preserves the cross-sectional area of the lumen. The area circumscribed by the internal elastic lamina (internal elastic lamina area) was taken as a measure of the area of the arterial lumen if no plaque had been present. The internal elastic lamina area correlated directly with the area of the lesion (r = 0.44, P less than 0.001), suggesting that coronary arteries enlarge as lesion area increases. Regression analysis yielded the following equation: Internal elastic lamina area = 9.26 + 0.88 (lesion area) + 0.026 (age) + 0.005 (heart weight). The correlation coefficient for the lesion area was significant (P less than 0.001), whereas the correlation coefficients for age and heart weight were not. The lumen area did not decrease in relation to the percentage of stenosis (lesion area/internal elastic lamina area X 100) for values between zero and 40 percent but did diminish markedly and in close relation to the percentage of stenosis for values above 40 percent (r = -0.73, P less than 0.001). We conclude that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area. The preservation of a nearly normal lumen cross-sectional area despite the presence of a large plaque should be taken into account in evaluating atherosclerotic disease with use of coronary angiography.

Body fat distribution as a risk factor for coronary artery atherosclerosis in female cynomolgus monkeys.

Central fat deposition is associated with increased risk of coronary heart disease morbidity and mortality in women. Subcutaneous fat distribution was investigated as a potential factor that might exacerbate diet-induced coronary artery atherosclerosis (CAA) in female cynomolgus monkeys (Macaca fascicularis) which share with North American Caucasian women a gender-related protection against CAA. In a retrospective necropsy study (n = 36), the distribution of the antemortem ratio of subscapular/triceps skinfold thickness was divided at the mean and the two resulting groups were designated high and low for this variable. CAA was quantified as the mean cross-sectional intimal area based on nine coronary artery sections. The extent of CAA was significantly greater in the high skinfold ratio group as compared to the low skinfold ratio group. Ponderosity was closely associated with the skinfold ratio but was not a useful predictor of CAA. These findings suggest that female cynomolgus macaques may provide a primate model of the health consequences of regional fat distribution in women.

Mechanism of luminal enlargement in PTCA and restenosis: a histopathological study of necropsied coronary arteries collected from various centers in Japan.

Necropsy studies of coronary arteries were made in 14 patients who died after percutaneous transluminal coronary angioplasty (PTCA). Eight patients died shortly after PTCA, while the other six patients died some considerable time later. A total of 9,920 serial step sections of necropsied coronary arteries at the site of PTCA were prepared and examined histopathologically by light microscope to determine the mechanism of luminal enlargement in PTCA, as well as the occurrence of restenosis. Of the eight patients who died shortly after PTCA, two had disruption of the intima and the media in the arterial wall located opposite the site that had atheroma, in spite of the fact that the former wall is more normal than the latter. Dissection of the media was camed out in four patients and intimal desquamation performed in six. All the patients revealed fresh thrombus formation. Of the six patients who survived for a long time after PTCA was performed, two had disruption of the intima and the media located opposite the site with atheroma. In one, the media was dissected and in another, intimal desquamation was camed out. In one patient, release of atheroma into the lumen was suspected. Proliferation of intimal cells was revealed in three patients indicating that restenosis had occurred. No compression of the atheroma was observed in any of the 14 patients. The above findings led to the conclusion that the mechanisms of luminal enlargement in PTCA are: 1) intimal and medial disruption in the arterial wall located opposite the atheroma; 2) medial dissection; 3) intimal desquamation; 4) release of atheroma into the lumen; and 5) any combination of 1) -4).

Rupture of a left ventricular papillary muscle during acute myocardial infarction: Analysis of 22 necropsy patients

Certain clinical and cardiac morphologic findings are described in 22 patients, aged 45 to 80 years (mean 64) (15 men [68%]), in whom rupture of a papillary muscle occurred during acute myocardial infarction. In most, the acute infarction associated with papillary muscle rupture was a first coronary event (only 18% had a myocardial scar consistent with prior infarction and 29% had angina pectoris). The posteromedial papillary muscle, presumably because of its more tenuous blood supply, ruptured almost three times more frequently than the anterolateral one (73 and 27%, respectively). Quantitative examination of the amounts of narrowing by atherosclerotic plaque in each of the four major epicardial coronary arteries (right, left main, left anterior descending and left circumflex) disclosed less narrowing in the patients with rupture than in the patients with fatal acute myocardial infarction unassociated with rupture. Of the 519 five mm sections of coronary artery examined (11 patients), only 68 sections (13%) were narrowed greater than 75% in cross-sectional area compared with 34% of 1,403 sections from 27 patients with fatal myocardial infarction without rupture.

Arterial intimal embrittlement A possible factor in atherogenesis

Sections of aorta, coronary artery, basilar artery and vena cava were collected at autopsy. Macroscopically normal intimal specimens were removed by stripping. Intimal collagen was measured as hydroxyproline. Intimal film embrittlement was measured in vitro by a bursting volume distensibility test developed in our laboratory. There was an average increase of over 100% in the collagen content of apparently lesion-free human arterial intima on aging over a fifty-year period. This includes an increase of 113% for aortic intima, 49% increase for coronary artery intima, and an increase of 158% in collagen in basilar artery intima. In contrast the collagen level in the vena caval intima decreases on aging, by 42% in fifty years. The large increase in collagen in arterial intima is accompanied by a large increase in intimal embrittlement. The decreasing collagen content of the venous intima on aging results in increased distensibility. Increased aortic intimal film embrittlement (lower distensibility) correlates with age ( R = 0.699), but even better with intimal collagen ( R = 0.911), suggesting that aortic intimal collagen level is a more important determinant of intimal embrittlement than age. Men, older than 55, have significantly higher aortic intimal collagen levels than women. Embrittlement of arterial intima should make it more susceptible to injury under the pulsatile pressure of the blood. Decreased venous intimal collagen and greater distensibility on aging could be factors in the development of venous valvular insufficiency and varicose veins. However, our study of veins was performed primarily as a control in this instance. Fundamental elements in the atherogenic process are increased intimal collagen, increased intimal brittleness, endothelial injury, followed by intimal cell proliferation. In the vena caval intima on aging there is decreased collagen, increased intimal distensibility, no injury due to increased pulse or blood pressure, and, therefore, no cell proliferation and no intimal lesion.