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Aortic valve sclerosis (AVS) is a chronic progressive disease involving lipid infiltration, inflammation, and tissue calcification. Despite its high prevalence, there are currently no clinically approved pharmaceuticals for the management of AVS. The objective of the current study was to elucidate the effects of an angiotensin II type 1 receptor blocker, alone or in combination with statin therapy, on the progression of AVS.

Background:Vascular smooth muscle cells (VSMCs) are a potential autologous cell source for aortic valve tissue engineering, but have a phenotype that differs from that of valvular interstitial cells in vivo. We hypothesized that combining basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), or platelet-derived growth factor (PDGF) with transforming growth factor beta-1 (TGF-β1) would achieve a valvular interstitial cell–like phenotype of VSMCs.Methods:VSMC phenotype was assessed by immunofluorescence, proliferation was measured by the tetrazolium reduction (MTT) assay, and extracellular matrix gene expression was determined by real-time polymerase chain reaction.Results:Combinations of growth factors that included PDGF showed the greatest increases in proliferation. Immunofluorescence for α-smooth muscle actin demonstrated an inverse correlation between proliferation and a myofibroblast-like phenotype, while combinations of TGF-β1+ EGF+bFGF (TEF) and TGF-β1+EGF+PDGF (TEP) induced the greatest change of α-smooth muscle actin expression compared to untreated controls. Finally, TEP treatment showed an increase in versican, fibronectin, and type I collagen mRNA expression, while decreasing matrix metalloproteinase 1 expression.Conclusions:Combination of TGF-β1 with EGF and PDGF induces VSMC proliferation and expression of extracellular matrix constituents found in the aortic valve. In vitropreconditioning of VSMCs provides a potentially viable surrogate cell source for developing a valve graft.

Background. Dehydration of tissue due to glutaraldehyde fixation has been reported and was examined in this study of porcine aortic valve cusps. The effect of altered hydration on cusp internal shear properties was also examined.

It has been suggested that collagen loss and damage is responsible for the dysfunction seen in stunned myocardium. To test this hypothesis we compared collagen in canine hearts stunned by repeated occlusion with collagen in hearts stunned by a single occlusion. Regional contractile function was equally depressed in both groups: segment shortening at 1 hour after reperfusion averaged 37% ± 9% versus 32% ± 9% of preocclusion values in repeated and single occlusion models, respectively. Midmyocardial collagen content was not different in either single occlusion (10.5% ± 0.4%) or repeated occlusion models (9.5% ± 0.7%) when compared with nonischemic hearts (8.5% ± 0.8%). Collagen damage, which was revealed with polarized light microscopy, was seen in 5 of 6 dogs after repeated occlusion but was not apparent after a single occlusion. Thus although both models of stunned myocardium produce similar dysfunction, there was no apparent collagen loss. Furthermore, collagen damage was only seen after repeated occlusion. Therefore it appears unlikely that collagen damage is a primary mechanism of stunned myocardium.

Objectives: To report quantitatively on the three-dimensional layered organization of the collagen and smooth muscle component of the two most successful vessels for coronary bypass—the internal mammary artery (IMA) and the long saphenous vein (SV). Our aim was to provide an explanation for the differential structural stiffness of these two vessels (both functioning at arterial pressures in their new environment), and how they might be susceptible to endothelial thickening. Methods: Eleven human saphenous veins and 23 internal mammary arteries were fixed at arterial distending pressure of 110 mmHg, and were sectioned in cross-section at 7 μm thickness. A subset of these was also sectioned tangentially. Measurements of the three-dimensional alignment of collagen and smooth muscle fibers within the vessel wall were made using polarized light microscopy and the universal stage attachment. Data were plotted and analysed using circular statistics. Results: The IMA, structured like an elastic artery, is dominated by a media with discrete lamellae of wavy collagen and smooth muscle, aligned nearly circumferentially, with a low variability of alignment (mean circular SD 12°). The SV is more variable in its size and structure, characteristically with a narrow circumferential media comprised mostly of collagen which is straightened and highly aligned at arterial pressures (mean circular SD 9°). Circumferential collagen in the vein was often adjacent to longitudinal bundles of smooth muscle and collagen. Conclusions: The strikingly aligned structure of the SV complements the known high mechanical stiffness of this vessel when at arterial distending pressure. The high fraction of longitudinal muscle, in addition to the circumferential muscle cells in the SV make it vulnerable to any pre-implant surgical preparation, and to the cyclical luminal pressures and longitudinal strains characteristic for epicardial arteries.

Reports indicate that cryopreserved aortic valve allografts have a better long-term survivability than other bioprostheses, such as the porcine xenograft. Unlike xenografts, allograft valves do not require treatment with glutaraldehyde and may therefore retain much of their original mechanical function. The effects of cryopreservation on the mechanical integrity of collagen fibers and mucopolysaccharides, however, are still largely unknown. We therefore compared the mechanical behavior of cryopreserved allograft leaflet material to that of fresh tissue and xenografts by measuring their bending stiffness (nine strips of tissue) and their uniaxial tensile stress/strain and stress/relaxation behavior (six strips of each tissue type). The bending tests showed no significant difference between the pliability of cryopreserved allografts and fresh pig aortic valve tissue, but the xenograft material was significantly stiffer than both (p <0.001). The mean circumferential tensile elastic moduli of the allografts, fresh tissue, and xenografts at a stress of 300 kPa were 9.1 ± 5.4 MPa, 13.0 ± 1.7 MPa, and 12.5 ± 3.0 MPa, respectively, and were not significantly different from each other. We also found that the transition from a low to a high modulus on the stress/strain curves, a measure of extensibility, occurs at 23%, 22%, and 12% strain for the three materials. There was no significant difference between the allograft and the fresh tissues, but the xenograft material was less extensible than the other two (p < 0.001). The xenograft tissue also had significantly lower rates of stress relaxation than the other two materials (p < 0.005). Thus no detectable differences were found between the mechanical behavior of the cryopreserved allograft aortic leaflets and fresh tissue, whereas the xenograft material was less extensible and less capable of relaxing than both the allograft and fresh tissue. The ability of allografts valves to respond to tensile and flexural stresses in a manner similar to that of the natural aortic valve may therefore contribute to their good in vivo survivability.

Six cases of left atrial myxoma were studied using transcutaneous, continuous-wave, low-frequency Doppler ultrasound. The recordings, made from the suprasternal notch and the cardiac apex, showed characteristic deflections that coincided with tumor motion and provided a useful ancillary technique for noninvasively confirming the echocardiographic diagnosis of atrial myxoma.

We evaluated 32 young patients with mitral valve prolapse (MVP) as the only recognized cause of cerebral ischemia. The mean follow-up from the time of the first ischemic event was 8 years. At the time of the follow-up evaluation, 24 patients (75) had a normal cardiac examination, and 4 had midsystolic clicks; only 1 had the characteristic clickmurmur. In 75, the first ischemic event was stroke. When MVP-associated ischemia was recognized, 44 had recurrent ischemic events. In the mean 4-year period between diagnosis of MVP-associated ischemia and follow-up, 16 had recurrent ischemic events, but none had a new persistent deficit from these events. At the time of follow-up, 63 of patients were taking platelet antiaggregants or anticoagulants. These data suggest a good prognosis for recurrent ischemic events after diagnosis of MVP-associated ischemia.

Regular tachycardia with wide QRS complexes may be difficult to classify as supraventricular (SVT) or ventricular (VT) without electrophysiologic studies. We felt that hemodynamic differences between VT and SVT should allow their distinction by echocardiography. In this study, we utilized high speed M-mode echocardiography in the usual projections in eight patients during tachycardia. Two patients had spontaneous VT and three had spontaneous SVT with aberrant conduction. The remaining three were patients in sinus rhythm undergoing electrophysiologic studies in whom right ventricular (RV) pacing (induced VT), right atrial (RA) pacing (induced SVT) and sequential RV-RA pacing (induced VT with 1:1 retrograde conduction) were carried out. The echocardiographic parameters studied included: left ventricular internal dimensions, time during which the mitral valve remained open (MVOT), left ventricular ejection time (LVET) and pre-ejection period. We measured 20 consecutive beats and for each parameter defined its variability. During A-V dissociation (VT, RV pacing) there was always a striking beat-to-beat variability in the values of MVOT (68 percent to 129 percent) and in LVET (41 percent to 175 percent). In contrast, during A-V association (SVT, sequential RV-RA pacing, sinus rhythm) the maximal variability of MVOT and LVET was 22 percent and 12 percent, respectively. Variability during A-V dissociation could be explained by asynchronous timing of atrial systole. We conclude that echocardiography can readily identify atrioventricular dissociation, a feature heavily in favor of a diagnosis of VT.

• In 205 patients with carotid transient ischemic attacks (TIAs) who underwent full angiographic and cardiac investigations, we found that ipsilateral carotid bruit and triggering of TIA by exertion or standing up suggested a carotid lesion. Angina pectoris or palpitations at onset of TIA suggested a cardiac source of emboli. Patients with only one TIA, multiple identical attacks, progression of symptoms over minutes, and appropriate infarct on computed tomograms (28%) were likely to show a potential arterial or cardiac cause for the TIAs in subsequent investigations. Transient monocular blindness correlated with carotid occlusion, but the severity of the carotid lesion did not influence the duration and repetition of attacks. Transient ischemic attacks in multiple territories, identical attacks, and multiple or silent infarcts on computed tomograms occurred equally in the patients with arterial lesions and those with cardiac lesions. These findings suggest that only a few, albeit important, conclusions regarding etiology can be drawn from the clinical characteristics of TIAs.

• Two hundred fifty consecutive patients with carotid transient ischemic attacks (TIAs) and no previous stroke were assessed with cerebral angiography (95%), two-dimensional echocardiography (86%), electrocardiography (100%), and Holter monitoring (99 selected patients). Angiography disclosed a lesion appropriate to the TIAs in 84%. Lesions also occurred in the asymptomatic carotid artery, but stenosis of more than 75% of the lumen diameter and ulcers were significantly more frequent on the symptomatic side. Twenty-three percent of the patients had a potential source of emboli from the heart, usually in the context of symptomatic heart disease. Among the 205 patients who underwent full angiographic and cardiac investigations, 6% had an isolated potential cardiac source of emboli and 19% had a potential cardiac source of emboli associated with appropriate carotid disease. The search for a potential cardiac source of emboli is strongly indicated in patients with carotid TIAs and known heart disease. In the patients with no history of heart disease, the yield of this search is low, but our results suggest that at least 14 of such patients have an undetected potential cardiac source of emboli. Cardiac and arterial lesions commonly coexist in carotid TIAs.

• Twelve patients who had no evidence of arteriosclerotic cerebral vascular disease, lacked hypertension or coagulation defect, and had not been receiving contraceptive therapy had recurrent transient cerebral ischemic attacks (TIAs) and partial nonprogressive strokes. All had prolapsing mitral valve proved by angiocardiography. The average age was 38 years, compared with 62 years in a larger series of patients with TIA associated with arteriosclerosis. We propose that the ischemic events are related to emboli emanating from the abnormal mitral valve with or without an associated paroxysmal cardiac arrhythmia.

Most of our knowledge of heart valve mechanics has been gained from low strain-rate studies much lower than physiologic levels. Using a high-speed materials testing system, we compared the low and high strain-rate viscoelastic behavior of porcine aortic valve cusps at extension rates of up to 40 mm/s. Circumferential and radial strips were stretched and then held in their stretched configuration to measure their “stressrelaxation” behavior. During low strain-rate stretching, only 6% of the initial stress dissipated or relaxed after 1 second, whereas 25% of the stress dissipated during high strainrate stretching. This considerable difference in stress relaxation suggests a ratedependent viscoelastic behavior that has not been accounted for in valve design and may have important implications for accelerated pulse testing. Even though the valve cusp is loaded for only 0.4 seconds during each heartbeat, at least 15% of the stress may relax over that period. During accelerated pulse testing, however, sufficient time may not be available to allow the tissue fibers to relax back to their natural state before the subsequent loading cycle, leading to a higher baseline preload. In addition, because valve tissue is not given sufficient time to relax before the next cycle, pulse testing subjects the valves to lowermagnitude cyclic stresses than does physiologic loading. Because both the baseline preload and the magnitude of cyclic stresses may lead to early fatigue failure, accelerated wear testing may either overestimate or underestimate valve durability. Clearly, the mechanism of stressinduced failure of biologic tissues must be elucidated before too much validity is placed on pulse duplicator studies.

Glutaraldehyde fixation noticeably alters the mechanical properties of porcine aortic valve tissue, subsequently affecting the function and durability of these tissues when used as prosthetic heart valves. Traditional uniaxial tensile testing techniques do not fully define the mechanical properties and we have devised a new approach to examine the important shear properties of the tissue. Altered shear properties would change the response of the valve tissue as it flexes open and closed. An apparatus combining a high-precision linear actuator with a gram-sensitive load cell was used to measure the shear characteristics of circular punch specimens taken from the center of each valve cusp. The tissue parameters measured showed significant differences between the fixed and fresh tissues. Glutaraldehyde-fixed tissue (n = 16) was about 100 times as stiff as fresh tissue (n = 32) between shear strain values of 0 and 0.2. The fixed tissue also had stress relaxation rates about 60% those of the fresh cusps and had about 70% of the hysteresis loss seen in fresh tissue. These results demonstrated the significant effects of glutaraldehyde fixation on the properties of porcine aortic valve cusp when tested in shear. Such changes could lead to altered tissue function and may increase internal stresses during opening and closing, contributing to valve fatigue.

An unusual case of Staphylococcus aureusendocarditis confined to the mural left atrium is presented. Echocardiographic studies revealed a 1.5 × 2.0-cm vegetation mimicking a myxoma situated in the path of a mitral regurgitant jet on a color Doppler test. Emboli to upper and lower extremities and brain complicated the patient's preoperative course. Surgical excision and pathologic examination confirmed this rare occurrence. (Chest 1991; 99:757–59)

The relative incidence of myocardial abscesses occurring in the presence of acute or chronic ischemic heart disease is unknown. Clinical presentation usually involves nonspecific signs of sepsis, and the diagnosis often becomes apparent only when extensive myocardial destruction has occurred. Early diagnosis can greatly reduce morbidity and mortality rates. Echocardiography is a readily accessible and accurate method of diagnosing abscesses both in the presence or absence of endocarditis. We describe the appearance of a myocardial abscess complicating myocardial infarction.

With the long term goal of improving our understanding of the mechanisms involved in coronary artery spasm, we have undertaken a two part study of the artery structure. We have made a comparison of the relative proportions of the different layers in proximal and distal regions of the main coronary arteries, and have quantitatively assessed their three dimensional structural fabric. Major coronary arteries from nine hearts were prepared for histological examination after fixation at a transmural pressure of 120 mm Hg. Measurements from 14 proximal and distal pairs of the cross sectioned arteries showed a dominant subendothelial layer, which diminished in thickness distally, with a small fraction of muscle cells interspersed with collagen. Three dimensional orientation measurements of the collagen and muscle components, which are birefringent, were obtained from one pair of segments from each of the left anterior descending, circumflex and right coronary arteries, using the polarising light microscope and Universal stage. Findings showed (1) a single circumferential order of adventitial collagen, with a mean circular standard deviation (CSD) of 22.3°; (2) very highly ordered medial smooth muscle, mean CSD of 5.0° (both findings are quantitatively similar between proximal and distal segments of artery, and between arteries); and (3) a multilayered fabric of collagen in the subendothelium in all vessel segments. The principal contributor to functional differences between proximal and distal regions may be the prominent and structurally varied subendothelial layer of the coronary arteries.

<$O_ST_ABS>AUTHORS SYNOPSIS<$C_ST_ABS>The dynamic viscoelasticity of the anterior leaflet of human mitral valves was investigated by subjecting the ventricular aspect of membranous samples of the tissue to sinusoidal fluid pressures. The frequency range of the stressing function used was from 0.5 Hz to 5 Hz. The storage modulus of the tissue was found to be independent of the stressing frequency and an average value of 2.55 (SE = 0.12) 108 dyn cm–2 was observed. Losses were small and the phase shift between stressing function and resulting strain and hence the loss modulus increased with frequency. For the frequency range investigated the phase shift varied from 0.04 to 0.06 rad and the loss modulus was of the order of 107 dyn cm–2. From the observed data it was concluded that any tissue substitute used in mitral valve replacement should be rather inextensible and have a low loss modulus. Also under normal physiological conditions, the mitral valve cannot bulge into the left atrium during peak ventricular systole and hence events in the cardiac cycle, such as the presence of the atrial pressure ‘c’ wave, that involve the distensibility of the valve need to be reexamined.