Short time insulin treatment post burn improves elastic-collagen rearrangement and reepithelization

Extensive burn may cause acute resistance to insulin, which accentuates hypermetabolism, impairs glucose metabolism, immune dysfunction and risks of sepsis. To minimize these effects, insulin is used as a treatment. The purpose was to analyze the collagen-elastic arrangement effects of insulin on the burned skin. Wistar rats were assigned in groups: control (C); control with insulin (C + I); scald burn injury (SBI); and SBI with insulin (SBI+ I). SBI were submitted to 45% total body surface area burn and the insulin-treated groups received insulin (5 UI/Kg/day) for 4 or 14 days (d). Insulin levels, glucose tolerance test and HOMA index were determined. The skin sections were analyzed for histophatological and morphoquantitative data. Histopathological findings showed increased reepithelization of SBI+ I and formation of a new muscle layer after 14 days. In the collagen-elastic arrangement, insulin for 4 days increased the volume fraction (Vv) of thin collagen and elastic fibers. After 14 days, independently of injury, insulin decreased the elastic fibers. Insulin was able to reverse damages in the collagen-elastic rearrangement and stimulate reepithelization after 4 days. Untreated scald-burned animals showed higher Vv of thick collagen after 4 days, while those treated had a higher Vv of thin collagen. The Vv of elastic fibers was increased in SBI+ I for 4 days. In conclusion, insulin treatment was able to stimulate reepithelization. It also reversed the damages to the collagen-elastic arrangement in the scald-burned group, improving the organization of thin collagen and increasing the Vv of elastic fibers in the injured group treated with insulin for a short time, that is, for 4 days.     

In vivo calcification of glutaraldehyde-fixed cardiac valve and pericardium of Phoca groenlandica

Calcification remains the main reason for failure of bioprosthetic valves. The aim of this study was to evaluate the in vivo calcification response of a new bioprosthetic valve, derived from cardiac tissue of Phoca groenlandica. Aortic and pulmonary leaflets, bovine, and Phoca groenlandica pericardia were fixed in buffered glutaraldehyde solution. Tissues were divided into four groups: group 1, bovine pericardium (BP); group 2, pulmonary leaflets; group 3, seal pericardium; and group 4, aortic leaflets. All samples were implanted subdermally into four sets of eight female 12-day-old Wistar rats for 21 days. The tissues were divided into two parts for calcium measurement, and histology with hematoxylin-eosin, von Kossa, and Weigert Van Gieson staining. All groups experienced significant calcification. Group 1 with 1.39 mg/g (0.34) before and 125.78 mg/g (21.48) after implantation (p < 0.001), group 2 with 1.50 mg/g (0.43) before and 151.85 mg/g (19.1) after (p < 0.001), group 3 with 3.15 mg/g (0.62) before and 116.38 mg/g (33.74) after (p < 0.001), and group 4 with 1.84 mg/g (0.52) before and 126.95 mg/g (13.37) after (p < 0.001). Explant samples showed foreign body response, disorganized collagen, and obvious calcification. The cardiac valve and pericardium of Phoca groenlandica calcify to the same extent as the BP.     

Treatment of bioprosthetic heart valve tissue with long chain alcohol solution to lower calcification potential

The use of glutaraldehyde-treated biological tissue in heart valve substitutes is an important option in the treatment of heart valve disease. These devices have limited durability, in part, because of tissue calcification and subsequent tearing of the valve leaflets. Components thought to induce calcification include lipids, cell remnants, and residual glutaraldehyde. We hypothesized that treatment of glutaraldehyde-treated bioprosthetic heart valve material using a short and long chain alcohol (LCA) combination, composed of 5% 1,2-octanediol in an ethanolic buffered solution, would reduce phospholipid content and subsequently lower the propensity of these tissues to calcify in vivo. Phospholipid content of glutaraldehyde-treated porcine valve leaflets and bovine pericardium was found to be 10.1 +/- 4.3 (n = 7) and 3.9 +/- 0.48 (n = 2) microg/mg dry tissue, respectively, which was reduced to 0.041 +/- 0.06 (n = 7) and 0.21 +/- 0.05 (n = 4) microg/mg dry tissue, respectively, after LCA treatment. Calcification potential of the treated tissues was assessed using a rat subcutaneous implant model. After 60 days of implantation, calcium levels were found to be 171 +/- 32 (n = 11) and 83 +/- 70 (n = 12) mg/g dry weight for glutaraldehyde-treated porcine leaflets and bovine pericardium, respectively, whereas prior LCA treatment resulted in reduced calcium levels of 1.1 +/- 0.6 (n = 12) and 0.82 +/- 0.1 (n = 12) mg/g dry weight, respectively. These data, taken together, support the notion that treatment of glutaraldehyde-treated tissue with a short and long chain alcohol combination will reduce both extractable phospholipids and the propensity for in vivo calcification.     

New treatments using alginate in order to reduce the calcification of bovine bioprosthetic heart valve tissue

Calcification limits the functional lifetime of cardiac valve substitutes fabricated from glutaraldehyde preserved bovine pericardium. Host factors, mainly younger age, and implant factors, mainly glutaraldehyde cross-linking, are implicated in the calcification process. Glutaraldehyde cross-linking is believed to activate the potential sites in the tissues for biocalcification. In the present work, we investigated the possibility of using alginate azide (AA) instead of glutaraldehyde for the preservation of pericardial tissues in order to enhance the durability of bioprosthetic heart valves. Grafting with poly(GMA-BA) copolymer to the alginate azide cross-linked pericardial (AACPC) tissue was carried out to obtain better stability, strength, and anticalcification properties. The strength property and thermal stability of the AA cross-linked tissues were studied. Calcification studies in rat subdermal models reveal that AA cross-linking reduces the calcification to negligible levels. After 30 days implantation, the calcium content was found to be 10.4 ± 1.2 and 6.1 ± 0.3 μg mg^-1 for untreated AACPC and polymer grafted AACPC, respectively, compared to a value of 100 ± 1.2 μg mg^-1 calcium recorded for control glutaraldehyde cross-linked pericardial (GCPC) tissues.     

“Vaso-muscular mediadysplasia” of the arteria vertebralis

Summary Report of a 48 year old woman with 15 years' history of arterial hypertension. Death due to dissecting aneurysm of the aorta with pericardial tamponade.A peculiar abnormality in the architecture of the vascular wall of the vertebral arteries was observed: A vascular valve and transluminal bands in the right vertebral artery and tortuous arteriolar vessels as well as cavernomatous venous vessels in the outer part of the media of both vertebral arteries. The direction of muscle fibers in these sites was abnormal. These abnormalities are interpreted as a hamartomatous malformation, for which the term: vaso-muscular mediadysplasia is proposed.     

Baroreflex control of renal sympathetic nerve activity and heart rate in near-term fetal sheep

Late preterm infants, born between 34 and 36 weeks gestation, have significantly higher morbidity than neonates born at full term, which may be partly related to reduced sensitivity of the arterial baroreflex. The present study assessed baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in near-term fetal sheep at 123 ± 1 days gestation. At this age, although fetuses are not fully mature in some respects (term is 147 days), sleep-state cycling is established [between high-voltage, low-frequency (HV) and low-voltage, high-frequency (LV) sleep], and neural myelination is similar to the term human infant. Fetal sheep were instrumented to record blood pressure (BP), HR (n = 15) and RSNA (n = 5). Blood pressure was manipulated using vasoactive drugs, phenylephrine and sodium nitroprusside. In both HV and LV sleep, phenylephrine was associated with increased arterial BP and decreased HR. In HV sleep, phenylephrine was associated with a fall in RSNA, from 124 ± 14 to 58 ± 11% (P < 0.05), but no significant change in RSNA in LV sleep. In contrast, the fall in BP after sodium nitroprusside was associated with a significant increase in HR during LV but not HV sleep, and there was no significant effect of hypotension on RSNA. These data demonstrate that in near-term fetal sheep baroreflex activity is only partly active and is highly modulated by sleep state. Critically, there was no RSNA response to marked hypotension; this finding has implications for the ability of the late preterm fetus to adapt to low BP.     

The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats

Immobilized bisphosphonates (BPs) have been introduced to improve implant fixation, however, no information could be found about the efficiency of this approach in osteoporotic bone. This study was designed to evaluate the bone response to surface immobilized BPs on implants inserted in tibiae of ovariectomized (OVX) rats. Three months after bilateral ovariectomy, 40 rats were randomly assigned into four groups for implantation of hydroxyapatite-coated titanium implants with or without immobilized BPs: (1) control group (without BP treatments); (2) pamidronate (PAM) group (1 mg/ml of PAM immersing); (3) ibandronate group (1 mg/ml of ibandronate immersing); and (4) zoledronic acid (ZOL) group (1 mg/ml of ZOL immersing). After implantation periods of 3 months, the peri-implant–bone density, trabecular microstructure, bone–implant interface and mechanical fixation of implants were evaluated by dual energy X-ray absorptiometry, micro-computed tomography, histology and push-out test. We found that three BPs triggered pronounced bone–implant integration and early bone formation around implants in OVX rats, with a rank order of ZOL > ibandronate > PAM. These results provide new evidence that immobilized BPs have positive effects on implant fixation in osteoporotic bone, in addition to their well-documented potency to inhibit implant loosening in normal bone.     

Calcification of bovine pericardium used in cardiac valve bioprostheses. Implications for the mechanisms of bioprosthetic tissue mineralization.

Calcification of bioprosthetic heart valves fabricated from glutaraldehyde-pretreated bovine pericardium has not been investigated. The objectives of this study were to characterize pericardium before and after glutaraldehyde pretreatment and to study the pathophysiology of mineralization of glutaraldehyde-preserved pericardium. Pericardial protein was approximately 90% collagen, predominantly Type I. Glutaraldehyde incorporation was complete following 24 hours' incubation (151 X 10(-9) mol/mg). Bovine pericardium pretreated in buffered 0.6% glutaraldehyde, implanted subcutaneously in young rats for 24 hours to 112 days, was analyzed chemically (calcium and phosphorus) and morphologically. Mineralization, detected at 48 hours' implantation, was initially associated with pericardial connective tissue cells and later also collagen. Mean calcium content was 114 micrograms/mg at 21 days and 199 micrograms/mg at 112 days. The morphologic features and the kinetics and degree of mineral accumulation in glutaraldehyde-pretreated bovine pericardium were strikingly similar to those previously determined for porcine aortic valve. These results predict that calcification will critically limit the late durability of clinical pericardial bioprostheses and suggest generalized mechanisms of bioprosthetic tissue mineralization which are probably dependent on modification of implant microstructure by glutaraldehyde pretreatment.     

Animal model of acute pericarditis and its progression to pericardial fibrosis and adhesions: Ultrastructural studies

To study the evolution of pericardial inflammation, we have developed a model of pericarditis in sheep by surgically injecting heat-killed staphy-lococci and Freund's adjuvant into the pericardial cavity under sterile conditions. The pericarditis evolved through the following phases: (1) inflammatory response, (2) mesothelial cell injury and desquamation, and (3) fibrotic phase. At 3–24 hr there was increased microvascular permeability, which resulted in the exudation of fluid, neutrophils, macrophages, ami fibrin into the pericardial cavity and the pericardial intersti-tium. By 72 hr, large numbers of inflammatory cells were aggregated on the mesothelial surfaces and dispersed throughout the pericardial cavity, either as free-floating cells or located between strands of fibrin. At 6 days, fibrinolysis was apparent along the mesothelial surfaces; and newly formed collagen fibrils were deposited throughout the interstitial spaces and among the aggregated cells. These fibrils provided a matrix for the growth of new blood and lymphatic vessels into new connective tissue on both parietal and visceral pericardial surfaces. At 2 weeks, intrapericardial fibrosis had produced focal adhesions between the pericardial surfaces. By 1 month, extensive areas of the pericardial cavity were obliterated. By 9 months, there was a marked reduction in the numbers of cells and blood vessels and increased deposition of collagen and elastic fibers. The intrapericardial injection of heat-killed staphylococci and adjuvant provides a reproducible animal model to study the time course of pericardial inflammation.     

Spatial variation in membrane excitability modulated by 4-AP-sensitive K+ channels in the axons of the crayfish neuromuscular junction

Current-clamp recordings were made from the primary (1°) and secondary (2°) branching points (BPs) of axons at the crayfish neuromuscular junction. Action potential (AP) firing initiated by current injected at the 2° BP showed strong adaptation or high-frequency firing at threshold current, whereas AP firing frequency at the 1° BP exhibited a gradual rise with increasing current amplitude. The voltage threshold for AP (V(TH)) was higher at the 2° BP than the 1° BP. 4-Aminopyridine (4-AP) at 200 μM increased AP amplitude and duration at both BPs but reduced threshold current at the 2° BP more than at the 1° BP. This blocker lowered V(TH) at both BPs, but the difference between the BPs remained. Firing patterns evoked at the 2° BP became similar to those evoked at the 1° BP in 4-AP. Thus 4-AP-sensitive channels may be more concentrated in the distal axon and control AP initiation and firing patterns there. Orthodromic APs between the two BPs were also compared. There was no difference in AP amplitude between the two BPs, but AP half-width recorded at the 2° BP was longer than that at the 1° BP. AP duration at both BPs increased gradually, by ～17%, during a 100-Hz, 500-ms train (in-train rise). Normalized AP half-widths revealed a smaller fractional in-train rise at the 2° BP. Thus, although distal APs were broader, AP duration there was under more stringent control than that of the proximal axon. 4-AP increased AP amplitude and duration of the entire orthodromic train and reduced the magnitude of the in-train rise in AP half-width at both BPs. However, this blocker did not uncover a clear difference between the two BPs. Thus 4-AP-sensitive channels concentrated in distal axon may be essential in preventing unintended firing and modulating AP waveform without interfering with orthodromic AP propagation.     

CT-scan images preprocessing and segmentation to improve bioprosthesis leaflets morphological analysis

The visualization of bioprosthesis leaflet morphology might help to better understand the underlying mechanism of dysfunction in degenerated aortic bioprosthesis. Because today such visualization of bioprosthesis leaflet morphology is intricate to impossible with other imaging techniques, we hypothesized that the processing of multi-detector CT images would allow better visualization of the prosthetic valve leaflets after biological aortic valve replacement. The purpose of our study was to prospectively evaluate patients with a degenerated aortic bioprosthesis, waiting for reoperation, by using 64-slice CT to evaluate prosthetic leaflets morphology. A semi-automatic segmentation of pre-operative tomodensitometric images was conducted, using 2 different implementations of the region growing algorithm. Here we report all segmentation steps (selection of the region of interest, filtering, segmentation). Studied degenerated aortic bioprostheses were represented by two Carpentier-Edwards Supra Annular Valve (porcine leaflets), one Edwards Perimount (pericardial leaflets) and one Medtronic Mosaic (porcine leaflets). Both segmentation methods (Isotropic Region Growing and Stick Region Growing) allowed a semi-automatic segmentation with 3D reconstruction of all bioprosthetic components (stent, leaflets, degeneration/calcifications). Explanted bioprosthesis CT images were also processed and used as reference. Segmentation results were compared by means of quantitative criteria. Semi-automatic segmentation using region growing algorithm seems to provide an interesting approach for the morphological characterization of degenerated aortic bioprostheses. We believe that in the next future CT scan images segmentation may play an important role to better understand the mechanism of dysfunction in failing aortic bioprostheses. Moreover, bioprostheses 3D reconstructions could be integrated into preoperative planning tools to optimize valve-in-valve procedure.     

Effect of family responsibilities and job strain on ambulatory blood pressure among white-collar women

OBJECTIVE: This study was conducted to determine whether large family responsibilities and their combination with high job strain were associated with an increase in ambulatory blood pressure (BP) among white-collar women. METHODS: A cross-sectional study was conducted in a stratified random sample of 199 white-collar women with or without children who were employed full time in jobs involving high or low strain. These women were selected from a population of 3183 women of all ages, employed in eight organizations in Quebec City, Canada. Subjects wore an ambulatory BP monitor for 24 hours during a working day. Mean BPs were calculated. Different measures of family responsibilities were used, based on the number of children and their ages, and domestic work. Job strain was measured using the Job Content Questionnaire recommended by Karasek. RESULTS: Family responsibility measures were significantly related to diurnal BP among women holding a university degree (N=69). Indeed, women having large family responsibilities had increases in systolic and diastolic BPs of 2.7 to 5.7/1.8 to 4.0 mm Hg (p< or =.05). Among women holding a university degree, increases in diurnal systolic and diastolic BPs reached 8.1 to 10.9/5.5 to 7.1 mm Hg (p< or =.01) among women having both large family responsibilities and high job strain. These results were independent of confounders. There was no significant association among women without a university degree (N=130). CONCLUSIONS: Large family responsibilities were associated with significant increases in diurnal systolic and diastolic BPs among white-collar women holding a university degree. In these women, the combined exposure of large family responsibilities and high job strain tended to have a greater effect on BP than the exposure to only one of these factors.     

Copper-induced hepatotoxicosis with hepatic stellate cell activation and severe fibrosis in North Ronaldsay lambs: a model for non-Wilsonian hepatic copper toxicosis of infants

Copper-sensitive North Ronaldsay sheep represent a possible model for certain hepatic-overload syndromes of infancy and childhood that are clinically, pathologically and genetically distinct from Wilson's disease. The purpose of this study was to simulate in artificially reared lambs the syndrome produced by copper exposure in susceptible human infants. Twenty four North Ronaldsay lambs were assigned to three groups of eight animals, namely, an unsupplemented control group and two trial groups given milk replacer to which copper (CuSO4) had been added at the rate of 5 mg/litre and 10 mg/litre. Four lambs from each group were killed at 40 or 69 days. Livers were fixed in 10% formalin and analysed for copper by mass spectrometry. Paraffin wax-embedded sections were stained with rhodanine for copper and labelled immunohistochemically for alpha smooth muscle actin (ASMA). At 40 days the maximum amounts of copper in the livers of both copper-supplemented groups was 1466-1605 microg/g dry weight (control group 172-201 microg/g Cu dry weight). Histochemically, copper was demonstrated within hepatocytes, together with marked apoptosis. At 69 days there was a florid pericellular fibrosis complemented by strong ASMA immunolabelling, confirming phenotypic modulation of hepatic stellate cells. Such primary copper-induced fibrogenesis confirms the unique status of this animal model in respect of childhood copper toxicosis.     

The Significance of Circulating and Cell-Bound Antibodies in Experimental Allergic Encephalomyelitis

Conjugates of horseradish peroxidase with myelin basic protein (BP) of guinea pig or Lewis rat were used to identify antibody-containing cells in draining lymph nodes during experimental allergic encephalomyelitis (EAE). Peroxidase activity was revealed for light and electron microscopic preparations with the diaminobenzidine reaction of Graham and Karnovsky. Basic proteins (BP) were also iodinated with ¹²⁵I for determination of circulating antibody against BP by radio-immunoassay of ¹²⁵I BP using coprecipitation with antirat IgG or with antirat serum proteins. Encephalitogenicity was lost after conjugation of guinea pig BP or Lewis rat BP with peroxidase, whereas iodination did not affect the encephalitogenicity of guinea pig or Lewis rat BPs. EAE was induced in Lewis rats with guinea pig or Lewis rat spinal cord BPs in complete Freund's adjuvant. Draining lymph nodes were studied by light and electron microscopy during the course of the immune reaction, and cells with specific antibody against BP were identified with the use of BP-horseradish peroxidase conjugates. Lymph node sections from animals immunized with high antigen doses (500 μg) showed numerous plasma cells with intracellular antibody against BP in medullary cords 10 days after immunization and 4 days prior to histologic appearance of EAE. Numbers of positive cells correlated with levels of circulating antibody against BP. Immunization with a low antigen dose (5 μg) resulted in EAE, few or no antibody-containing cells, and significantly lower levels of circulating antibody. Brown Norwegian rats, a strain resistant to EAE, immunized with 500 μg of BP had positive cells in draining lymph nodes and high levels of circulating antibody against BP in the absence of histologic evidence of EAE. Lewis rats injected with Lewis rat small BP failed to develop EAE. Nevertheless, these animals showed levels of circulating antibody and antibody-containing cells similar to those of animals which developed EAE after injection of the mixture of Lewis rat large and small BP. It is concluded that although the BP-peroxidase labeling method reveals cells with specific anti-BP antibody, these cells are probably unrelated to EAE. The lack of correlation between EAE induced by low antigen doses and levels of circulating anti-BP antibody (determined with the use of highly encephalitogenic ¹²⁵I-BP) suggests that effector cells can be stimulated at low antigen doses, but higher antigen doses are required to induce the production of levels of circulating antibody detectable by the method of immune coprecipitation.     

Monoclonal antibodies reactive with myelin basic protein

New monoclonal antibodies (MAbs) to myelin basic protein (BP) reveal epitopes to be in sequences 22–34, 75–82, 83–96, 118–131 and 125–131. Comparison of these results with those previously reported suggest that almost every sequence of about 10 amino acid residues may be sufficiently antigenic to make a single MAb but that certain regions are immunodominant, strong enough to make practically the same MAb repeatedly. One of these new MAbs (clone 3) has especially interesting reactivity, sharply limited to residues 75–82 in bovine and porcine BP: Lys-Ala-Gln-His-Gly-Arg-Pro. Whales presumably have the same sequence, since their BPs are fully reactive with clone 3 MAb, but all other species of BP, with known sequences of BP, have at least two changes in this sequence. Deletion of Lys⁷⁵ (as in a tryptic peptide of porcine BP) reduces reactivity with the MAb about 10-fold, whereas substitution of Ala⁷⁶ by Ser (as in all other species of BP) and either deletion of Gln⁷⁷ (as in human, monkey and rabbit BP) or His⁷⁸ (as in the guinea pig and rat BP) or substitution of Pro⁸² by Thr (as in human, monkey, rat and mouse BP) eliminates reactivity. We speculate that woodchuck and prairie dog BPs in this region closely resemble chicken BP, which has about 2% of the original reactivity. However, squirrel BP is unique, probably having only one of the changes in this region of BP, since it possesses 10–20 times the reactivity of chicken BP but still only 20–50% of the original reactivity with clone 3 MAb, a degree of reactivity not seen with any other species of BP.     

Explant culture of human peripheral lung. I. Metabolism of benzo[alpha]pyrene

Human lung explants have been maintained in vitro for a period of 25 days. Autoradiographic studies indicated that the broncholar epithelial cells, type 2 alveolar epithelial cells, and stromal fibroblasts incorporated 3H-thymidine during the culture. After 7 to 10 days, type 2 cells were the predominant alveolar epithelial cell type. Lamellar inclusion bodies were released from the type 2 cells and accumulated in the alveolar spaces. The metabolism of benzo[alpha]pyrene (BP) in human lung explants cultured for up to 7 days was investigated. Human lung explants had measurable aryl hydrocarbon hydroxylase activity and could metabolize BP into forms that were bound to cellular DNA and protein. Peripheral lung had significantly lower aryl hydrocarbon hydroxylase activity than cultured bronchus but both tissues had similar binding levels of BP to DNA. Radioautographic studies indicated that all cell types in the peripheral lung can metabolize BP. The major ethylacetate extractable metabolites of BP formed by peripheral lung were tetrols and trans-7,8-diol. The primary water-soluble metabolite released with arylsulfatase and beta-glucuronidase was 3-hydroxybenzo[alpha]pyrene.     

Mechanism of Pericardial Expansion with Cardiac Enlargement

Background: The normal pericardial sac accommodates a 250–350 gram heart and 15–50 ml of pericardial fluid. Cardiac enlargement and/or increases in fluid must be accompanied by an increase in pericardial volume and a concomitant expansion of the pericardial sac. The mechanism of such expansion has been debated, but theoretical considerations include fibroblastic proliferation with new connective tissue deposition versus remodeling of the pre-existent connective tissue. Design: Nineteen pericardia were obtained from consecutive adult autopsies. Total pericardial fluid was measured; the absolute value of pericardial fluid volume and cardiac weight were added to create a total score. Representative pericardial tissue was stained with hematoxylin-eosin (H&E), Masson's trichrome, and Verhoeff's elastin stain (EVG). An additional archival case with the pericardium from a 900-g heart with 1,000-ml of fluid was also included. Results: None of the sections showed histologic evidence of fibroblastic proliferation. Parameters indicative of collagen stretching or damage were evaluated. The greatest correlative factor in identifying an enlarged pericardium was the average of four measurements of the greatest distance between elastic fibers surrounding obliquely oriented collagen layers. Five of six cases with a cardiac score >450 showed an average measurement of less than 15 μ, and 10 of 14 cases with a cardiac score ⩽450 showed an average measurement of >15 μ (p = 0.0498). Histologic and ultrastructural evidence of collagen damage was identified in the pericardium from the 900-g heart with the 1,000-ml effusion. Conclusions: We propose that collagen stretching and slippage of obliquely oriented collagen layers contribute to the increased surface area needed to accommodate larger volumes. When these limits are exceeded, collagen damage ensues.     

Observations on Cardiac Output in Animal Experiments and Clinical Application of Jiuling Bileaflet Mechanical Valve Prosthesis

Objective:To observe the cardiac output(CO)in animals and patients undergone valve replacement with Jiuling bileaflet mechanical valve prosthesis.Methods: 1.Animal experiments:6 sheep that subjected to mitral replacement with a 21-mm-valve prosthesis were measured by open cardiac catheterization intraoperatively. Echocardiographic and open cardiac catheterization under dobutamine stress were performed on 2 sheep survival for 30 months post-operation.2.Patient measurements:CO of 14 cases of aortic valve and 10 cases of mitral valve was measured by open cardiac catheterization,and after 12 months,it was measured by echocardiography.Results:1. Animal experiments:The mean CO of 6 sheep was 2.5 L/min intraoperatively by catheterization,and that of 2 sheep survival for 30 months post-implant was 3.0 L/min by echocardiography and 2.9 L/min by catheterization,respectively.2.Patient measurements: The mean cardiac index of 4 patients with 21 mm valve replacement was(2.55±0.27) L/min/m2by catheterization,and was(2.84±0.13)L/min/m2 by echocardiography after 12 months.Conclusion:This study demonstrates that cardiac function on animals and patients return to normal activity after undergone the valve replacement,and the newly valve prosthesis shows excellent hemodynamic performance.     

Influence of different chemical cross-linking treatments on the properties of bovine pericardium and collagen

The use of biological materials in the construction of bioprostheses requires the application of different chemical or physical procedures to improve the mechanical performance of the material without producing any undesirable effects. A number of cross-linking methods have been tested in biological tissues composed mainly of collagen. The basis for most of them is the use of glutaraldehyde (GA), which acts on the Lys or Hyl residues. We have studied the effects of alternative chemical treatments: diphenylphosphorylazide (DPPA) and ethyldimethylaminopropyl carbodiimide (EDAC). Their mechanism of action is based on the activation of the carboxyl groups, which then permits their cross-linking to amino groups. As a control, we employed conventional treatment with GA, applying it to bovine pericardium and collagen membranes removed from bovine pericardium. The analysis of the Lys and Hyl residues showed that DPPA and EDAC produced 50% of the chemical change provoked by GA. This value was even lower in the trials with collagen. In terms of the resistance to collagenase degradation, chemical cross-linking with GA provided much greater protection in both materials (3.81 +/- 3.47 nmol of amino acid/mg dry tissue for pericardium and 4.41 +/- 1.13 nmol of amino acid/mg dry tissue for collagen). Treatment with DPPA also protected pericardium (13.11 +/- 6.57 nmol amino acid/mg dry tissue) although the values for collagen was lower (50.0 +/- 32.4 nmol amino acid/mg dry tissue). Treatment with EDAC was much less protective than the other two chemical reagents (43.28 +/- 17.4 and 55.85 +/- 14.57 nmol amino acid/mg dry tissue for pericardium and collagen, respectively). The degree of tissue calcification after implantation of the chemically treated materials into young rats was considerably greater for GA and DPPA (32.9 +/- 18.8 and 36.3 +/- 13.3 mg g(-1) dry tissue, respectively) than with EDAC (18.0 +/- 7.2 mg g(-1) dry tissue; P < 0.001). After 60 days of implantation, the values for GA and EDAC were higher(124.1 +/- 31.3 and 124.6 +/- 21.0 mg g(-1) dry tissue, respectively) versus 34.6 +/- 19.2 mg g(-1) dry tissue for DPPA. There were no significant differences in collagen levels in samples treated with GA or EDAC after 30 days of implantation, although both groups showed significant differences when compared with DPPA-treated samples (P < 0.001). After 60 days of implantation, there were no significant differences among these three treatments in terms of the calcium accumulated on samples.     

Effects of parental history of hypertension and urbanization on blood pressure in zimbabweans

The increasing prevalence of essential hypertension is a growing public health concern for Zimbabwe and other African countries. Two important risk factors for hypertension are urbanization and parental history of hypertension. The relations among parental history of hypertension, urbanization, and blood pressures (BPs) are poorly understood. The objective of this study is to clarify these relations in a population of urbanized. African, young adults. The relation between parental history of hypertension and urbanization on resting BPs and BP responses to a menial arithmetic stressor was examined in a group of normotensive, Black medical students with (n = 36) and without (n = 34) a parental history of high BP.and with (n = 49) and without (n = 19) a parental history of urbanization. Results indicate that those with a positive parental history of high BP had higher resting BPs and greater systolic blood pressure (SBP) increases in response to laboratory stress, when compared to their negative parental history counterparts. Further, those with parents residing in urban areas had higher resting SBPs than those with parents residing in rural areas. However, no reactivity differences were apparent between the urban and rural parent groups. These data suggest that although parental history for hypertension influences both resting and reactivity BPs, parental history of urbanization may influence only resting BP. This study was supported by NIH/Fogarty International Center Grants 5T37TW3041-02, N1H-HL35195. and NIH-HL32738.