Degeneration and calcification of bioprosthetic cardiac valves. Bioprosthetic tricuspid valve implantation in sheep.
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Animals↗
Biomedical subjects
V J Ferrans
Publications and source records attributed to V J Ferrans.
Intracuspal hematomas in implanted porcine valvular bioprostheses: clinical and experimental studies.
Intracuspal hematomas were found in three of 57 porcine valvular bioprostheses implanted as substitute cardiac valves in 50 patients and in 11 of 29 similar bioprostheses implanted in sheep. The three values implanted in patients had been in the mitral position for 27, 65, and 107 months. Of the valves implanted in sheep, six had been in the mitral position and five in the tricuspid position for periods of time ranging from 20 minutes to 7 months. In each patient and in four of 11 sheep, the hematomas involved more than one cusp. These lesions were localized in the spongiosa, extended from the basal region toward the free edge of the cusp, and formed a plane of dissection which involved the spaces left in the spongiosa by the removal of proteoglycan material during preimplantation commercial processing. In one patient, the hematomas limited the mobility of the cusps and appeared to have been the cause of clinically significant prosthetic mitral stenosis; in the other two patients and in the experimental animals, the hematomas were smaller and of uncertain hemodynamic significance. Intracuspal hematomas may become sites of eventual formation of calcific deposits. The pathogenesis of intracuspal hematomas is related to the entry of blood into the space between the sewing ring and the most basilar region of the bioprosthetic tissue. This space extends throughout the circumference of the bioprosthesis and is continuous with the spongiosa, the layer in which the hematoma develops. The blood penetrates into this space through the suture line between bioprosthetic tissue and sewing ring on the inflow surface of porcine valvular bioprostheses which have been mounted on atrioventricular type stents. Intracuspal hematomas were not found in bioprostheses mounted on aortic type stents, in which these sutures are more protected and more closely spaced, or in pericardial bioprostheses, which do not have a spongiosa.
Adolescent↗
Calcifications of cardiac valve bioprostheses. Biochemical, histologic, and ultrastructural observations in a subcutaneous implantation model system.
To study the process of calcification in bioprosthesis, 108 glutaraldehyde-treated porcine aortic valve leaflets were implanted subcutaneously in rabbits and removed 1 day to 6 months later; morphologic findings were correlated with biochemically determined levels of calcium (Ca++) and gamma-carboxyglutamic acid (Gla), a vitamin K-dependent Ca++-binding amino acid known to be present in a variety of tissues with pathological calcification. Gla and Ca++ levels began to increase about 2 months after implantation and increased progressively with time. Ca/Gla molar ratios were comparable to those in leaflets of bioprostheses explanted from patients, 22 to 64 months after implantation. Morphologically evident calcification began at the same time that Gla and Ca++ increases were detected biochemically and also increased in severity with time. Electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the interfibrillar spaces. The biochemical and morphological findings in this experimental system are similar to those described in calcified porcine bioprosthetic valve leaflets removed from patients, but occurred much more rapidly. As with pathological calcification of other tissues, progressive calcification was accompanied by increased Gla levels, suggesting that Gla plays a role in the calcification of the leaflets. This model allows rapid comparative evaluation of large numbers of valve leaflets maintained under similar host conditions.
1-Carboxyglutamic Acid↗
Bioprosthetic valvular failure. Clinical and pathological observations in an experimental animal model.
We compared the clinical, hemodynamic, and morphological findings in 18 young sheep in which porcine valvular bioprosthesis (eight animals) and bovine pericardial bioprostheses (10 animals) were implanted in the tricuspid position. At the time of terminal elective studies (mean of 5.2 +/- 0.2 months after implantation), six animals had ascites, 16 had hepatic congestion, and four had bioprosthetic valvular infection. Hemodynamic studies (n = 10) showed that the tricuspid transvalvular mean diastolic gradients were not different at implantation and at termination of the study (4.7 +/- 0.8 versus 4.9 +/- 0.9 mm Hg); however, tricuspid valve end-diastolic gradients increased from 1.2 +/- 0.6 to 3.9 +/- 0.5 mm Hg (p less than 0.01). Each of the 18 valves had calcific deposits. Quantitative studies revealed that implanted porcine valvular bioprosthesis (n = 7) contained a mean of 323 +/- 165 mg of calcium/gm of dry weight of cuspal tissue, in contrast to 0.2 mg/gm in unimplanted porcine valvular prostheses. Similarly, implanted bovine pericardial bioprostheses (n = 6) contained a mean of 421 +/- 115 mg of calcium/gm of dry weight of cuspal tissue, in contrast to 0.3 mg/gm im unimplanted bovine pericardial bioprostheses. Morphological findings in both types of bioprostheses included calcific deposits, collagen degeneration, leaflet immobilization and retraction, and fibrous sheaths. The latter were more extensive in bovine pericardial bioprostheses than in porcine valvular bioprostheses. We conclude: (1) that the pathological alterations which develop in bovine pericardial bioprostheses are generally similar to those in porcine valvular bioprostheses, but may be more severe; (2) that these alterations lead to physiological and clinical sequelae similar to those of bioprosthetic valvular failure in human subjects; and (3) that young sheep constitute an excellent experimental model for in vivo testing of bioprosthetic cardiac valves.
Animals↗
Failure of porcine aortic and bovine pericardial prosthetic valves: an experimental investigation in young sheep.
Seventeen porcine aortic and 10 bovine pericardial bioprosthetic valves were implanted in the tricuspid position in 27 young sheep. Clinical, hemodynamic and morphologic evaluations were performed after a mean of 4.7 +/- 0.3 months (range 3-7 months) after implantation. Eight sheep developed ascites (five with porcine aortic and three with bovine pericardial bioprosthetic valves); all 27 sheep had microscopic evidence of hepatic congestion. Three porcine and three bovine valves became infected. Hemodynamic studies (n = 15) performed immediately after implantation and at the time of terminal elective studies showed that tricuspid valve end-diastolic gradients increased from 0.7 +/- 0.4 mm Hg to 4.5 +/- 0.5 mm Hg (p less than 0.01). All 27 valves had calcific deposits. By quantitative analyses, unimplanted cuspal tissue (n = 9) had 0.6 +/- 0.1 mg/g of calcium/g tissue dry weight; explanted porcine aortic valves (n = 16) had 182 +/- 74 and bovine pericardial valves (n = 6) 421 +/- 115 mg/g of calcium/g of tissue dry weight (NS for porcine aortic vs bovine pericardial valves). Morphologic findings were similar in both porcine aortic and bovine pericardial valves, and consisted of calcific deposits, collagen degeneration, microthrombi and fibrous sheaths. These findings are almost identical to those associated with bioprosthetic valvular failure in humans. In our experimental study, we found no significant differences in the development of calcification in porcine aortic and bovine pericardial bioprosthetic valves.
Animals↗
Intracuspal hematomas in bioprosthetic valves: pathologic findings and clinical implications.
The presence of intracuspal hematomas (ICHs) was investigated in 156 valvular bioprostheses, including 57 (all porcine aortic valvular bioprostheses) that had been implanted in patients and 99 (64 porcine aortic valvular bioprostheses, 29 bovine pericardial bioprostheses and six human dura mater bioprostheses) that had been implanted in sheep. ICHs were found in three mitral bioprostheses in patients and in 14 porcine aortic valvular bioprostheses (nine mitral and five tricuspid) in sheep. Hematomas were not found in the dura mater or pericardial bioprostheses. In each patient and in six of the 14 sheep, the hematomas involved more than one cusp and consisted of erythrocyte accumulations in the spongiosa. They extended from the basal region toward the free edge of the cusp and formed a plane of dissection that involved the spaces left in the spongiosa by removal of proteoglycan material during commercial processing. ICHs may become sites of formation of calcific deposits. ICHs result from entry of blood into the space between the sewing ring and the most basilar region of the bioprosthetic tissue. This space extends throughout the circumference of the bioprosthesis and is continuous with the spongiosa, the layer in which the hematoma develops. The blood penetrates this space through the suture line between bioprosthetic tissue and sewing ring on the inflow surface of porcine valvular bioprostheses mounted on atrioventricular-type stents. ICHs were not found in porcine valvular bioprostheses mounted on aortic-type stents, in which the sutures are more protected and more closely spaced, on in bioprostheses constructed of tissues (parietal pericardium and dura mater), which lack a spongiosa.
Adolescent↗
Ultrastructural alterations in allylamine- induced cardiomyopathy: early lesions.
Ultrastructural studies were made of the early changes induced in left ventricular myocardium by allylamine given to rats either in drinking water (10.7 mM for 1 to 7 days) or by gavage (100 mg. per kg. per day for 1 or 2 days). Rats on the drinking water protocol developed myocardial alterations evident by light and electron microscopy within 2 days; those given allylamine by gavage developed lesions after 24 hours. The earliest alteration consisted on interstitial edema and "activation" of interstitial cells possessing an oblong shape, abundant rough endoplasmic reticulum, occasional lysosomes, a prominent Golgi apparatus, few mitochondria, and large irregular nuclei (often with a typical "Anitschkow" morphology). Mitoses of these interstitial cells were frequent. Mitoses were also observed in endothelial cells. Acute myocardial necrosis, which developed after 6 days of the drinking water protocol or one gavage dose, was characterized by focal myofibrillar degeneration with lipid droplet accumulation and Z-line distortion and dissolution, especially prominent in areas of intercellular junctions. These focal lesions coalesced to involve whole myocytes with severe myofibrillar degeneration and contraction band necrosis. Mitochondria of severely altered cells were swollen and contained dense inclusions. Nuclei had prominent nucleoli and, in severely necrotic cells, clumped and irregular chromatin. Large areas of necrotic myocardium showed extravasated red blood cells and minimal intra- and extracellular deposition of fibrin. Vascular necrosis or thrombosis was not seen. A prompt inflammatory infiltrate was composed predominantly of macrophages invading necrotic myocytes, with occasional polymorphonuclear neutrophilic and eosinophilic leukocytes.
Allylamine↗
Ultrastructural alterations in the fibrous sheath, endocardium, and myocardium of dogs shocked with chronically implanted automatic defibrillator leads.
Catheter-mounted automatic implantable defibrillator leads were implanted in 10 dogs for 11 to 21 months (mean 15.0 months). Single shocks of 10 A, 20 A, or 30 A (peak current) were then delivered through the chronically implanted leads. Two days after the shock, the dogs were euthanatized and necropsied. The intracardiac segment of the lead was covered by a fibrous sheath, the endocardium in contact with the lead was thickened by fibrous tissue, and shock-induced myocardial necrosis was present surrounding the distal pair of electrodes, with the largest amount of damage found in the dogs given the large shocks. Ultrastructurally, the fibrous sheath was covered by endothelium and contained numerous spindle cells and identified as smooth muscle cells by their prominent cytoplasmic filaments and external laminae or myofibroblasts with prominent endoplasmic reticulum. The spindle cells were surrounded by abundant collagen fibrils but not by elastic fibers. The thickened endocardium contained numerous fibroblasts, abundant collagen fibrils, and a few small elastic fibers. The shock-induced myocardial alterations included necrosis of cardiac muscle cells with prominent mitochondrial mineralization, interstitial edema, and infiltration of macrophages.
Animals↗
Myocardial ultrastructural alterations in ducklings fed tellurium.
Seventy newly hatched ducklings were fed a commercial ration with 500 mg of added Te (as tetrachloride)/kg of feed for up to 28 days. Ducklings were euthanatized at day 14, 21, and 28, the hearts were studied by gross, microscopic, and ultrastructural examination. Cardiac damage was apparent grossly as hydropericardium and myocardial hemorrhage. Histopathologically, the ventricular myocardium had areas of acute hemorrhagic necrosis (often with mineralization), edema, and congestion. Resolving areas of necrosis appeared cellular with macrophages, heterophils, fibroblasts, and pale vacuolated cells with large vesicular nuclei that were identified as dedifferentiated myocytes. Ultrastructurally, necrotic fibers had disrupted contractile material and mineralized mitochondria. In resolving lesions, macrophages were numerous in the interstitium and within necrotic fibers. Also, a population of sublethally injured myocytes was present and appeared as dedifferentiated cardiac muscle cells with few myofibrils, scattered free filaments, prominent sarcoplasmic reticulum, abundant glycogen, and large nuclei with prominent nucleoli. These dedifferentiated myocytes represented a reparative phase of the Te-induced myocardial injury which has been termed "reactive hyperplasia" and "rejuvenating reorganization" in previous models of myocardial damage.
Animals↗
Occurrence and significance of endothelial cells in implanted porcine bioprosthetic valves.
Histologic and scanning and transmission electron microscopic studies were made to determine the frequency of occurrence of endothelial cells in 49 porcine valve bioprostheses removed from 43 patients 2 days to 113 months (average 35 months) after implantation. Endothelial cells were found in none of 17 bioprostheses in place for less than 1 year, in 5 (23 percent) of 22 in place for 1 to 5 years and in 7 (70 percent) of 10 in place for longer than 5 years. The 12 bioprostheses in which endothelial cells were present had been implanted in the atrioventricular position (7 of 32 in the mitral position and 5 of 6 in the tricuspid position) for 21 to 113 months (average 71). Endothelial cells were not found in any of 11 bioprostheses implanted in the semilunar position (9 in the aortic position and 2 in pulmonary conduits); however, all but one of these bioprostheses had been in place for less than 5 years. Endothelial cells were concentrated along the basal regions of the cusps. These cells did not grow in direct contact with valve collagen, but were attached to fibrin, thrombi or fibroelastic host tissue (fibrous sheath) on the valve surfaces. The growth of endothelial cells and associated fibrous tissue may serve to increase the structural stability of bioprosthetic valve cusps, which may be of functional importance several years after implantation when the porcine connective tissue may have undergone significant deterioration.
Adult↗
Structure and classification of cuspal tears and perforations in porcine bioprosthetic cardiac valves implanted in patients.
Morphologic studies were made of cuspal tears and perforations in 16 porcine valve bioprostheses that had been implanted in 14 patients (9 male and 5 female) ranging in age from 2 to 65 years. Eleven bioprostheses had been in the mitral position for 30 to 123 months, four in the aortic position for 15 to 40 months and one in a varied pulmonary conduit for 96 months. The cuspal lesions were classified into four types. Type I lesions, which involved the free edges of the cusps, were the most common of all lesions and occurred with equal frequency in mitral and aortic bioprostheses. Regardless of position of implantation, type I lesions were more frequent in the right coronary cusp than in the other cusps. Ultrastructural study showed that these lesions develop as consequences of breakdown of collagen at the free edges of the cusps, usually near the commissures. Type II lesions consisted of linear perforations that extended along the basal regions of the cusps, forming an arc parallel to the sewing ring. These lesions were uncommon an resulted from separation of bundles of collagen. Type III lesions, which were large, round or oval perforations that occupied central regions of the cusps, were more common in aortic than in mitral bioprostheses. They were characterized by marked destruction of cuspal tissue and were most frequently associated with infection. Type IV lesions were small pinhole-like perforations; they usually were multiple, localized in central regions of the cusps and associated with calcific deposits. Type IV lesions were more common in mitral than in aortic bioprostheses. Regardless of position, they were more frequent in the left and noncoronary cusps than in the right coronary cusp (which may be protected by its muscle shelf against this type of perforation). It is concluded that cuspal tears and perforations develop in implanted bioprostheses as consequences of structural failure of connective tissue components.
Adolescent↗
Interstitial lung disease: current concepts of pathogenesis, staging and therapy.
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Adrenal Cortex Hormones↗
Study of the mechanism of hydralazine-induced myocardial necrosis in the rat.
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Animals↗
Divergent effects of propranolol and furosemide pretreatment on acute cardiomyopathy induced by minoxidil in beagle dogs.
Previous studies have shown that oral administration of minoxidil on 2 consecutive days produces an increase in heart rate and myocardial necrosis in Beagle dogs. Propranolol treatment (1.0 or 3.0 mg/kg every 8 h) did not abolish tachycardia and did not alter the incidence or severity of minoxidil-induced necrosis. In the present studies, pretreatment with either furosenmide (10 mg/kg) or hydrochlorothiazide (250 mg/kg) reduced serum potassium levels. However, only furosemide (for 11 days) reduced significantly the incidence of minoxidil-induced necrosis; only 2 of 10 animals (20%) developed myocardial lesions compared to 11 of 14 (79%) in the non-treated group. The incidence and severity of lesions in hearts from animals treated with furosemide for 3 days or hydrochlorothiazide for 11 days were essentially the same as in animals given minoxidil alone. Thus, furosemide, under certain conditions, can reduce the incidence of acute ventricular lesions induced by minoxidil.
Animals↗
Calcific deposits developing in a bovine pericardial bioprosthetic valve 3 days after implantation.
Calcific deposits, localized in a thin layer of thrombus covering the cuspal surfaces, were present 3 days after implantation in a valved pulmonic conduit that contained an Ionescu-Shiley bovine pericardial valve and was placed in a 29-year-old man with double outlet right ventricle, valvular and infundibular pulmonic stenosis, and ventricular septal defect. Factors that may have contributed to such a rapid calcification were the relatively young age of the patient, the development of acute renal insufficiency postoperatively, and the administration of large amounts of calcium chloride intravenously during blood transfusions and during episodes of cardiac arrest.
Adult↗
Minoxidil and cardiac lesions.
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Heart Atria↗
Characterization of the inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease.
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Adult↗
Hereditary emphysema in the tight-skin (Tsk/+) mouse.
The tight-skin (Tsk/+) mouse represents an autosomal dominant mutation characterized by increased thoracic size, large lungs, and a variety of abnormalities of loose subcutaneous connective tissue, cartilage, tendon, and bone. Because an increase in the size of the lung and thorax may result from destruction of alveolar walls and a loss of elastic recoil of the lung, the present study was undertaken to determine if the Tsk/+ mouse exhibits morphologic and physiologic characteristics of emphysema. In contrast to the lungs of normal mice, examination of the lungs of Tsk/+ mice by light and scanning electron microscopy revealed generalized enlargement of air spaces with numerous subpleural cysts and scattered bullae. In addition, many alveolar walls were either markedly thinned or broken and there was an increase in the number and size of the pores of Kohn. Consistent with these morphologic observations, the lungs of the Tsk/+ mice also exhibited physiologic characteristics consistent with emphysema. Compared to the lungs of normal mice, the lungs of Tsk/+ mice had a markedly increased total lung capacity of (1.8 +/- 0.1 ml versus 3.3 +/- 0.1 ml, p less than 0.001); compliance (0.077 +/- 0.006 ml/cm H2O versus 0.345 +/- 0.025 ml/cm H2O, p less than 0.001), and specific compliance (4.23 +/- 0.34% TLC/cm H2O versus 10.64 +/- 1.01% TLC/cm H2O, p less than 0.001). These findings suggested that the Tsk/+ mouse is a genetically determined model of emphysema that may be useful in determining the pathogenesis of destructive lung disease.
Animals↗