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[Immunogenicity of acellular bovine pericardium in vivo].

To investigate the feasibility of making up bovine pericardium into scaffolds for tissue engineering valve, it was decellularized by 0.5% trypsin incubation for three hours. The rats were divided into fresh bovine group, acellular pericardium group and control group, and OD value of rat anti-bovine IgG was measured. Serum levels of IgG showed no difference among the three groups on the 7th day postoperatively (P > 0.05). The OD values of IgG at other time-points displayed distinct difference among the three groups (P < 0.05). Fresh bovine pericardium group produced more IgG than acellular bovine pericardium group did at the same time-point. The IgG level of fresh bovine pericardium group reached the peak postoperatively, but in acellular bovine pericardium group its peak value appeared on the 30th day postoperatively. Histological examination demonstrated that the bovine pericardium was thoroughly decellularized, the fibrous structure was slightly loose, but remained essentially intact. These results indicate that the acellularization procedure can result in a complete removal of cells and decrease of immunogenicity.

Animals↗

[Morphofunctional characteristics of the hemomicrocirculatory bed of the canine pericardium].

The hemomicrocirculatory bed in the canine pericardium is presented by arterioles, precapillaries, capillaries, postcapillaries and venules situating in various connective tissue layers of the pericardium. Certain morphological peculiarities of the structure of the hemomicrocirculatory bed links are revealed in various parts of the pericardium. As demonstrate morphometry data, the diameter of all the vessels of the hemomicrocirculatory bed in various parts of the pericardium has no precise differences. There are some fluctuations in the number of the capillaries per 1 mm2 in various parts of the pericardium. Their number is comparatively greater in the area of the vascular porta (transitional fold), in the left lateral, in the ventral and dorsal parts of the pericardium. In these parts of the pericardium the density of the capillaries is increased, the network is especially dense in the area where the pericardial transitional fold passes into the epicardium. In the pericardial microcirculatory blood bed adaptive mechanisms (glomeruli, arteriolo-venular anastomoses, microsphincters) performing regulation of the organ's blood stream, are widely presented.

Animals↗

Prevention of calcification of glutaraldehyde pretreated bovine pericardium through controlled release polymeric implants: studies of Fe3+, Al3+, protamine sulphate and levamisole.

Calcification is the principal cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. The present study investigated controlled-release implants for prevention of the calcification of glutaraldehyde pretreated bovine pericardium in a rat subdermal model. Either Al3+ and Fe3+ (inhibitors of the growth and dissolution rate of hydroxyapatite crystals), levamisole (alkaline phosphatase inhibitor) or protamine sulphate (charge modifier) were individually incorporated into various polymeric carriers (either silicone rubber, polyurethane or silicone rubber-polyurethane copolymer). Polymeric implants were evaluated for in vitro release kinetics, which revealed that sustained drug release was obtained from 21 d to more than 90 d from various drug matrices. In vivo efficacy was studied by co-implanting the polymeric delivery systems with glutaraldehyde pretreated bovine pericardium for 21 d using a subdermal rat model; glutaraldehyde pretreated bovine pericardium calcium levels were quantitated by atomic absorption spectroscopy in the explanted tissues. Fe3+ and Al3+ polymeric implants were the most effective for inhibiting deposition of calcium mineral. Al3+ demonstrated 82% inhibition of calcification compared to controls and Fe3+ resulted in 80% inhibition of calcification. Specific histologic staining methods showed that Fe3+ and Al3+ were localized within the devitalized cells of the explanted glutaraldehyde pretreated bovine pericardium. No adverse effects on somatic growth or recipient bone morphology were noted following controlled-release drug administration. Controlled release of protamine sulphate or levamisole did not significantly inhibit glutaraldehyde pretreated bovine pericardium calcification. It is concluded that regional controlled release of Fe3+ or Al3+ inhibits glutaraldehyde pretreated bovine pericardium calcification in the rat subdermal model without adverse effects.

Aluminum↗

Posterior mitral annuloplasty using autologous pericardium in the repair of posterior leaflet prolapse.

OBJECTIVE: Mitral valve repair is frequently performed now because it produces a favorable postoperative quality of life, as well as improved cardiac function. For the treatment of posterior leaflet prolapse, we perform a posterior mitral annuloplasty using an autologous pericardium. The present study assessed the efficacy of this operation. METHODS: From April 1999 to October 2003, 42 patients underwent a posterior mitral annuloplasty using autologous pericardium for the treatment of posterior leaflet prolapse. There were 15 men and 27 women with an average age of 63.9 +/- 11.8 years. The length of the autologous pericardium matched the length of the posterior leaflet annulus as measured with Carpentier-Edwards ring sizer that was chosen based on the area of the anterior leaflet. RESULTS: The average size of the Carpentier-Edwards ring sizer that was used to determine the length of the autologous pericardium was 27.7 +/- 13 mm, and the absolute length of the pericardium was 50.9 +/- 1.8 mm, and the average intraoperative jet area, as assessed by transesophageal echocardiography, was 0.36 +/- 0.47 cm2. The five-year freedom from reoperation was 97.1%, while the freedom from significant residual mitral regurgitation (> or = 3+/4+) was 92.0%. Two patients (4.8%) developed systolic anterior motion, and one patient (2.4%) had a cerebral infarction. None of the patients died after surgery, and no patients developed complications such as hemolysis or ring detachment. CONCLUSIONS: Posterior mitral annuloplasty using an autologous pericardium was shown to be a superior technique because it allows a sufficient annular repair with no complications such as hemolysis or ring detachment.

Echocardiography↗

Influence of the pericardium on left ventricular diastolic pressure-volume curves in dogs with sustained volume overload.

The pericardium is largely responsible for displacement of the left ventricular diastolic pressure-volume curve observed after acute volume loading in dogs. Likewise the pericardium has been considered likely to play a role in displacement of the curve in patients with acute cardiac failure and in shifts following manipulation of afterload. This study was designed to examine the influence of the pericardium on the diastolic pressure-volume relation of the left ventricle when volume load is more sustained, a setting relevant to observations made in patients with heart failure. We measured left ventricular pressure and volume in six conscious dogs with sustained volume overload (mean left ventricular end-diastolic pressure 21 mm Hg, left ventricular end-diastolic volume 149% of the upper limit of normal for our laboratory) produced by aortocaval shunt created 7 to 29 days earlier. Simultaneous left ventriculograms and pressures were obtained before and during nitroprusside infusion with the pericardium intact and in four dogs the studies were repeated 7 to 15 days after pericardiectomy. In all six dogs with intact pericardium, nitroprusside displaced the entire pressure-volume curve downward whereas after pericardiectomy, the pressure-volume data points obtained before and during nitroprusside infusion fell on a single curve. These results were similar to those previously reported for acute volume overload. Nitroprusside did not alter the time course of left ventricular pressure fall during the isovolumic period of diastole either before pericardiectomy (28.8 +/- 10.2 sec,-1, 28.4 +/- 11.9 sec-1) or after (28.8 +/- 6.7 sec-1, 26.1 +/- 7.2 sec-1). These data indicate that in dogs subjected to volume overload sustained for periods of up to 29 days, the pericardium affects the left ventricular diastolic pressure-volume curve and contributes to the elevation of left ventricular filling pressure through upward displacement of this curve.

Animals↗

Modelling of the heart and pericardium at end-diastole.

Herein we present a refined version of Vito's two-sphere static model of the heart with pericardium and discuss its possible applications. The improvements we make on Vito's model are: (i) Vito assumed that the elastic materials which constitute the model 'heart' and 'pericardium' are isotropic; we relax this assumption to that of transverse-isotropy. (ii) Our analysis, which does not assume the existence of stored-energy functions, links the model directly to empirical stress-strain relations of suitable biaxial uniform-extension tests; two such stress-strain relations (one for the pericardium, one for the myocardium, both of which may be described by the same equation except for difference in the values of response parameters) now define the model completely, so we avoid altogether the difficult task of determining full-fledged constitutive equations for the pericardium and myocardium. As for applications, we contend that the concentric spheres in static equilibrium can be taken as a model of the left ventricle and pericardium at end-diastole. We show that the model when equipped with suitable stress-strain relations does give good fit to the pressure-volume data which Spotnitz et al. (1966, Circulation Res., 18, 49-66) obtained from excised canine left ventricles and to the pericardium data which Pegram et al. (1975, Circulation Res., 9, 707-714) obtained from closed chest, anaesthetized dogs. Three different empirical formulae were tried in the data-fitting as the equation that describes the requisite stress-strain relations. The 'exponential law' gave the best results.

Animals↗

Hybrid biomaterials based on the interaction of polyurethane oligomers with porcine pericardium.

Hybrid biomaterials have been produced by the interaction of polyurethane oligomers with both fresh and glutaraldehyde-fixed porcine pericardium. The hybrid biomaterials so formed were translucent with occasional white streaks and/or spots, had increased stiffness (to touch) but remained pliable. No shrinkage temperature was detected for fresh porcine pericardium hybrid up to 100 degrees C compared to porcine pericardium (approximately 67 degrees C) and glutaraldehyde-fixed porcine pericardium (approximately 87 degrees C). Amino acid analysis of the fresh porcine pericardium hybrid showed a reduction in lysine content after active isocyanate-terminated polyurethane oligomers exposure, indicating cross-linking between the polymer and tissue. Histological examination of the hybrid material shows a thin grey coating on both surfaces of the tissue, implying at least surface cross-linking of the tissue with polyurethane. The results suggest that fresh porcine pericardium can be reacted with active isocyanate-terminated polyurethane oligomers to produce hybrid biomaterials with covalent bonding.

Animals↗

Biaxial mechanical properties of human pericardium and canine comparisons.

The two-dimensional mechanical properties of human pericardium from seven males undergoing coronary artery bypass surgery were studied. A 25-mm square piece of parietal pericardium overlying the right ventricle was excised. An approximately 8-mm square target was marked at the center, and its dimension was measured electrooptically. When immersed in physiological saline at 37 degrees C, the specimen was subjected to biaxial isotropic loading. Large deformations developed in the beginning of the loading; the pericardium became increasingly stiffer when load was increased, and then became almost inextensible. As in canine pericardium [Lee et al., Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H222-H230, 1985], hysteresis was present and tension-stretch relationship was insensitive to loading frequency during cyclic loading, relaxation of tension was substantial, and creep was insignificant. Unlike canine specimens, however, human pericardium was nearly isotropic and almost three times as thick [mean 0.55 +/- 0.02 mm (SD)]. The human tension-area relation for isotropic loading could be described by an exponential function and was found to shift significantly to the left of the canine. Therefore, human pericardium is less extensible than canine.

Adult↗

Restraining effect of intact pericardium during acute volume loading.

To determine the effect of the intact pericardium on ventricular end-diastolic pressures (EDP) during acute volume loading, we measured left ventricular (LV) and right ventricular (RV) micromanometer pressure and LV volume using a conductance catheter in eight open-chest, anesthetized dogs. A range of LV pressure and volume was obtained by intravascular volume expansion with the pericardium intact and then over a similar range after removal of the pericardium. Pericardial pressure (Pper) was calculated using static equilibrium analysis as the difference between LVEDP with the pericardium present and absent at a constant LV volume. At the beginning of the fluid infusion (LVEDP 7.3 +/- 1.7 mmHg and RVEDP 4.4 +/- 2.6 mmHg, mean +/- SD), Pper was not different from zero (-1.0 +/- 2.3 mmHg, P not significant). The onset of pericardial restraint (Pper greater than or equal to 0 mmHg) occurred when LVEDP was 9.1 +/- 2.9 mmHg and RVEDP was 4.1 +/- 2.9 mmHg. At low cardiac volumes before fluid infusion, RV transmural pressure was positive and significantly greater than the near zero Pper. After the onset of pericardial restraint, however, RVEDP and Pper increased similarly and were related according to Pper = 1.1 (+/- 0.34) RVEDP - 4.2 (+/- 2.6) mmHg, standard deviation 0.6 +/- 0.8 mmHg, r = 0.98 +/- 0.10. These data indicate that the intact pericardium behaves in two functionally distinct ways. At low cardiac volumes, Pper is zero and the pericardium does not affect LV filling. RV transmural pressure is positive and greater than Pper.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Two-chain factor VIIa generated in the pericardium during surgery with cardiopulmonary bypass : relationship to increased thrombin generation and heparin concentration.

Several recent studies have proposed that coagulation is triggered during cardiopulmonary bypass surgery by extrinsic pathway activation involving factor VIIa generation, but the methodology was indirect. Therefore, 12 patients were studied during routine cardiac and cardiopulmonary bypass surgery. Samples were taken before, during, and after bypass from the perfusate, from the aorta (retrograde cardiac drainage), pericardium, and collected suction fluid originating from the whole operative field. These samples were analyzed by enzyme-linked immunosorbent assay for 2-chain factor VIIa, by prothrombin F1+2 assay, by thrombin-antithrombin (TAT) assay, and for heparin concentration. Factor VIIa, F1+2, and TAT levels in samples from the pericardium were greatly elevated (mean, 0.92 to 1.01, 227 to 334, and 399 to 526 microg/L, respectively; preoperative mean, 0.33, 32.3, and 1.90 microg/L, respectively; P<0. 05 for all), whereas levels in suction fluid were less consistently high. Factor VIIa and both F1+2 and thrombin-antithrombin levels in samples from the aorta, pericardium, and suction fluid were significantly correlated (r=0.57, P<0.001, n=111; and r=0.51, P<0. 001, n=105, respectively), and all were inversely correlated with heparin levels (r>-0.35, P<0.001, n>92). There was no evidence of factor VIIa generation in the circuit during bypass surgery, and both F1+2 and thrombin-antithrombin levels rose only approximately 2-fold, probably because heparin levels were higher than they were in the pericardium (P<0.05). We concluded that appreciable activation of factor VII occurs on the pericardium and that this is associated with increased thrombin generation. Ineffective local heparinization may be partly responsible. These results suggest that pericardium-induced activation of factor VII should be the target of anticoagulant strategies during cardiopulmonary bypass surgery.

Aged↗

Magnetic resonance imaging differentiated partial from complete absence of the left pericardium in a case of leftward displacement of the heart.

A 44-year-old man was referred to hospital for the evaluation of atypical chest pain. His chest X-ray showed leftward displacement of the heart. During echocardiography, the apical window displaced laterally in the usual left lateral position and characteristic motions of the interventricular septum and left ventricular posterior wall were recognized with postural alterations. We presumed a complete absence of the left pericardium. Magnetic resonance imaging (MRI), however, demonstrated a partial left-sided pericardium. The diagnosis was corrected to partial absence of the left pericardium and we have carefully followed up this case without surgical prophylactic intervention. It is very important to differentiate partial from complete absence of the pericardium, because only in patients with partial absence of the pericardium is there a risk of fatal myocardial strangulation. The features of the chest X-ray and echocardiography of this case, which strongly suggested complete absence of the left pericardium, are possibly not always reliable signs. In cases with these abnormal imaging features, MRI may provide additional useful information, as in this case.

Adult↗

CT dimensions of the normal pericardium.

Previous studies have suggested that the upper limit of the thinnest portion of the pericardium is 3-4 mm using 10 mm CT slices. However, these studies suffered from small sample sizes, long data acquisition times and unconventional viewing parameters. We have measured the width of the thinnest portion of the normal pericardium using 10 mm (100 patients) and 1 mm (100 patients) high resolution CT (HRCT) slices with modern CT equipment and fixed mediastinal window settings (400/20). The pericardium was identified in all patients and was best seen anterior to the heart. The pericardium is exceptionally well seen using 1 mm HRCT slices and this may be the optimal technique for visualization of the pericardium. The upper limit of the thinnest portion of the normal pericardium (mean value + 2 SD) was 1.2 mm (10 mm CT slices) and 0.7 mm (1 mm HRCT slices). These values are substantially lower than those previously reported and in line with anatomical findings.

Adolescent↗

Effect of pericardium on regional myocardial systolic function in acute ischemia.

To know whether or not the pericardium affects regional myocardial systolic function in acute ischemia, we measured ischemic and non-ischemic segment lengths of the left ventricle using ultrasonic crystals in 10 open-chest dogs with the pericardium preserved. When the left ventricular pressure and segment lengths were stable after left circumflex coronary occlusion, we opened the pericardium widely. After coronary occlusion, end-diastolic length (EDL) in ischemic and non-ischemic segments increased, and the ischemic segment showed paradoxical systolic expansion while the non-ischemic segment increased its active shortening. After pericardiectomy, heart rate, left ventricular systolic pressure, and peak positive and negative dP/dt did not change. EDL in ischemic and non-ischemic segments further increased from 12.02 +/- 0.18 to 12.50 +/- 0.16 mm (mean +/- S.E., p less than 0.01) and from 11.12 +/- 0.20 to 11.45 +/- 0.18 mm (p less than 0.05), respectively, despite the concomitant fall in left ventricular end-diastolic pressure (LVEDP) from 12.4 +/- 0.6 to 10.6 +/- 0.8 mmHg (p less than 0.01). End-systolic length in ischemic and non-ischemic segments also increased from 12.37 +/- 0.25 to 12.70 +/- 0.20 mm (p less than 0.05) and from 8.50 +/- 0.13 to 8.74 +/- 0.13 mm (p less than 0.01), respectively, although the left ventricular end-systolic pressure did not change. Maximum expanded systolic length of the ischemic segment also increased from 12.99 +/- 0.20 to 13.42 +/- 0.16 mm (p less than 0.01). These results indicate that, in acute ischemia, the pericardium inhibits paradoxical systolic expansion of the ischemic region and increase in end-systolic length of non-ischemic segment. Thus, it is concluded that the pericardium modifies the regional myocardial systolic function in acute ischemia, perhaps through the mechanical restraint of the pericardium.

Animals↗

Structure of bovine parietal pericardium and of unimplanted Ionescu-Shiley pericardial valvular bioprostheses.

To obtain a basis for the evaluation of postimplantation changes in bioprostheses made of parietal pericardium, we conducted comparative histologic, scanning and transmission electron microscopic studies of the structure of (1) normal bovine parietal pericardium, (2) glutaraldehyde-treated pericardial patches to be used for repair of cardiac defects, and (3) pericardial tissue cusps of unimplanted Ionescu-Shiley valves. Bovine parietal pericardium has three layers: (1) the serosa, or mesothelial cell layer; (2) the fibrosa, formed by diversely oriented, wavy bundles of collagen and by elastic fibers, and (3) the epipericardial connective tissue layer, which is partly continuous with the pericardiosternal ligaments. Pericardial patches and pericardial bioprosthetic cusps differ from normal pericardium by being denuded of mesothelium but they have normal degrees of waviness in their collagen. In Ionescu-Shiley valves, the inflow and outflow surfaces of each cusp correspond to the epipericardial and serosal surfaces of parietal pericardium, respectively. The inflow surfaces have a coarse texture, characterized by large bundles of collagen, and the outflow surfaces have numerous grooves, 10 to 30 mu in width and 20 mu in depth, which probably result from pressure exerted on the cuspidal surfaces by cotton material either during manufacturing or packing of the valves. Comparisons of the structure of bioprosthetic pericardial cusps and porcine aortic valve cusps show that the latter have reduced degrees of collagen waviness and a different layered structure: A layer similar to the spongiosa of aortic valve cusps is not present in pericardium. The functional implications of these observations are discussed in detail.

Animals↗

A novel annuloplasty system with rigid and flexible elements: initial experimental results in sheep and the case for untreated autologous pericardium.

BACKGROUND AND AIMS OF THE STUDY: A precise annuloplasty is difficult to perform with pericardium as the ring material because unwanted plication of the pericardium itself typically occurs when the sutures are tied. A novel annuloplasty system has been developed which should allow a predictably precise measured plication of the annulus without plication of the pericardium itself. A feasibility study was designed to evaluate this new concept. METHODS: Three juvenile sheep underwent implantation of a new annuloplasty system into the posterior mitral annulus without tissue annulus plication. Small rigid titanium suture-platforms 7 x 3 x 1 mm with two-suture holes 3 mm apart were individually affixed to the posterior mitral tissue annulus each with a single horizontal mattress suture. A longitudinal strip of untreated autologous pericardium, corresponding to the perimeter dimension of the free edge of the anterior leaflet, was sutured to the posterior annulus including both fibrous trigones, covering the suture-platforms with the mesothelial surface up, using two different suture techniques. No postoperative anticoagulation was utilized. Serial transthoracic echocardiograms and necropsy at five to six weeks post implant were performed. RESULTS: When the pericardium was affixed to the annulus with a continuous suture exposing only the mesothelial surface to the blood, completely covering the suture-platforms and their suture knots or folded in upon itself as a tube above the suture-platforms, it appeared to maintain all of its original implant dimensions and flexibility. There was no functional or anatomical distortion of any part of the mitral apparatus; fibrotic reaction was minimal and there was no thrombus formation with this suture technique. CONCLUSIONS: This annuloplasty system, combining rigid and flexible elements, 'melts' into the tissue annulus with a low profile, providing overall annular flexibility with no shrinkage of the overlying untreated autologous pericardium, no distortion of any part of the mitral apparatus, minimal fibrous reaction and no thrombus formation.

Animals↗

Appearance of the normal pericardium on coronary MR angiograms.

We evaluated the appearance of the normal pericardium on breath-hold MR images used to visualize coronary arteries. A coronary MR angiogram was obtained in 23 subjects (17 healthy volunteers and six patients with no known pericardial disease) using a breath-hold K-space segmented gradient-recalled echo sequence with fat suppression. Each coronary MR angiographic study included imaging planes equivalent to the following echocardiographic planes: four-chamber view, vertical two-chamber view, and two short-axis views (at base and mid ventricular level). The average pericardial thickness was 1.7 mm (range, 1.5-2.0 mm), and an average length of 60 mm (range, 20-110 mm) of pericardium was visualized. A significantly longer portion of the pericardium was seen in the vertical two-chamber view and the basal short-axis view than in the two other views (P < .001). Normal anatomic variations and overlapping structures and image artifacts can alter the appearance of the pericardium. Breath-hold MR imaging techniques used for coronary MR angiography allow routine, time-efficient evaluation of large portions of the pericardium.

Adolescent↗

The effect of ethylenediaminetetraacetic acid on calcific degeneration in bovine pericardium.

Calcification is the most frequent cause of the clinical failure of bovine pericardium bioprosthetic valves, preventing their widespread application for surgical treatment. The aim of this study was to minimize calcific degeneration in bovine pericardium by using a chelating agent, ethylenediaminetetraacetic acid (EDTA). Freshly excised bovine pericardium was dissected free from adhering fat tissue and cut into 1-cm(2) pieces that were rinsed in phosphate-buffered saline solution (PBS) and transferred into 4 degrees C PBS containing 1% glutaraldehyde (GA) for initial fixation, then allocated into two groups. Group I received the same treatment in a fresh solution for 5 more days. Group II underwent an additional fixation step in PBS solution (pH 7.4, 37 degrees C) containing 11% EDTA for a period of 48 h (30 ml/g tissue) and was then transferred into freshly prepared PBS + 1% GA solution at 37 degrees C for another 3 days. To investigate the calcification rate, pericardial patches were inserted into the dorsal pouches of 25 male Wistar rats for 21 days. Calcium levels were measured with an atomic absorption spectrophotometer and examined histo-pathologically. The calcium content of EDTA-treated pericardium (Group II), 21 +/- 3.8 microg/mg, was significantly lower than that of Group I, 43.3 +/- 9.2 microg/mg. Assessment of the degree of calcification in the histological sections generally agreed well with the results of the chemical analyses. Calcium deposition in Group I samples were found to be solid mineral depositions, whereas in the Group II pericardial samples, only smaller traces of calcium were found. Calcific degeneration in bovine pericardium can be reduced by using chelates such as EDTA.

Animals↗

Jugular phlebogram in congenital absence of the pericardium.

The purpose of this study was to emphasize the diagnostic value of the jugular phlebogram in congenital absence of the pericardium. Phonocardiographic study was performed in seven patients with complete absence of the left pericardium and in four with partial pericardial defect (left sided in three, right sided in one). Associated heart lesions were absent in all patients. The characteristic features of the jugular phlebogram in these patients were decreased depth of x descent and tall v wave followed by deep y descent (M-shaped pattern). These jugular abnormalities were more prominent in complete absence of the left pericardium than in partial pericardial defect. The x descent was completely obliterated in two patients with complete left pericardial defect. Loss of decrease in pericardial pressure during ventricular ejection and altered cardiac position as a result of the absence of the pericardium may be responsible for these jugular abnormalities. Jugular venous M-shaped pattern may be one of the useful physical and phonocardiographic indicators for the diagnosis of congenital absence of the pericardium.

Adolescent↗