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Biomedical subjects

V J Ferrans

Publications and source records attributed to V J Ferrans.

At least 163 records · Page 9Linked to original sources
PubMed1990

Immunohistochemical study of fibronectin in experimental myocardial infarction.

Light microscopic immunohistochemical studies were performed to evaluate the distribution of fibronectin in paraffin sections of p-formaldehyde-fixed normal rat hearts and the hearts of rats that had undergone ligation of the left coronary artery. A peroxidase-labeled antibody technique was used, together with appropriate immunohistochemical control procedures, for the localization of fibronectin in normal hearts and in the hearts of sham-operated animals. Fibronectin was localized in the interstitial space between myocytes, and beneath arterial, venous, and capillary endothelium. At 4 hours after coronary ligation, fibronectin was localized in a patchy fashion in the cytoplasm and interstitial space of some of the myocytes in the area supplied by the ligated vessel. At 24 hours, there was more intense, homogeneous staining in necrotic myocytes in the infarcted area and in the capillary endothelium in the border zone. At 48 hours, the intensity of staining for fibronectin was maximal in and between the necrotic myocytes in the center of the infarct and in proliferating and migrating capillaries and fibroblasts in the border zone. Similar patterns of localization were observed at 3 and 7 days after coronary ligation, but with progressive decreases in the intensity of staining. Two sources of fibronectin appeared to have contributed to these changes: plasma fibronectin diffusing through damaged blood vessels would account for the early staining observed in necrotic myocytes in the center of the infarct, whereas de novo synthesis of fibronectin by connective tissue cells and endothelial cells in sprouting capillaries would be responsible for the subsequent staining observed in viable capillaries in the border zone of the infarct. Known properties of fibronectin in vitro, combined with these in vivo observations, indicate that fibronectin may influence the thrombotic, inflammatory, angiogenic, and fibrotic processes involved in infarct healing.

Animals↗
PubMed1990

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. II. Modification of early changes by platelet inhibition with aspirin and dipyridamole.

The objective of this study was to determine the early influence of platelet inhibition on the histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. All animals received in combination aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. In animals subjected to platelet inhibition, cholesterol content in the graft was 170 +/- 52 micrograms/100 mg at 90 days, 205% of the level in ungrafted vein (p less than 0.01). This change was small in comparison with the increase to 686% of ungrafted vein observed in our study of control animals. In stepwise regression analysis, cholesterol content of grafts was best predicted by prevalence of foam cells (r2 = 0.82), and the proportion of intima as a fraction of total wall area was best predicted by the presence of macrophages (r2 = 0.69). Platelet inhibition did not decrease the extent of intimal hyperplasia. The prevalence of adherent platelets (r = -0.72) and the amount of fibrin (r = -0.78) correlated inversely with the amount of endothelium present during the first 14 days. The strength of these correlations declined with time, despite persistent lack of endothelium in some areas. Medial fibrosis occurred to the same extent as in control grafts, as did the early appearance of platelet factor VIII and fibronectin and the lack of vasa vasorum at 3 days followed by reappearance at 7 days. These data demonstrate that platelet inhibition dramatically reduces lipid uptake by grafts in the first 90 days but has less influence over histologic or morphometric changes.

Animals↗
PubMed1990

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. I. Sequential changes within the first three months.

The objective of this study was to define the histologic and morphometric evolution that accompanies the increase in cholesterol content of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys (Macaca arctoides), which were fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. Cholesterol content increased from 69 +/- 24 micrograms/100 mg (mean +/- standard deviation) in ungrafted vein to 473 +/- 122 micrograms/100 mg in grafts 90 days after implantation (p less than 0.05). By stepwise regression analysis, cholesterol content was best predicted by abundance of foam cells (r2 = 0.82). Intima comprised 13% +/- 5% of the total cross-sectional area of the wall in ungrafted vein and 59% +/- 11% at day 90 (p less than 0.001). With cholesterol content excluded from the stepwise regression, intimal area was best predicted by the presence of foam cells (r2 = 0.39). There was consistently an increase in the prevalence of polymorphonuclear leukocytes on the luminal surface and in both the intima and media during the first 14 days after grafting. Vasa vasorum, which were always present in ungrafted vein, were sparse at 3 days but reappeared by day 7. Medial fibrosis occurred in grafts, and in the 30- to 90-day interval it was directly correlated with the number of adventitial vasa vasorum present (r = 0.64, p less than 0.05). Immunohistochemistry revealed prominent staining for both platelet factor VIII and fibronectin during the first month, with a gradual decline in staining intensity thereafter. The evolution of changes in vein bypass grafts documented in this report are in general agreement with graft changes observed in humans and support the validity of our model in evaluating the histologic correlates of increased graft cholesterol content.

Animals↗
PubMed1990

Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. III. Long-term changes and their modification by platelet inhibition with aspirin and dipyridamole.

The objectives of this study were to elucidate the long-term influence on vein bypass grafts of platelet inhibition and its late discontinuation. Cephalic vein grafts were interposed bilaterally in the femoral arteries of stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Fifteen animals were divided into three groups of five animals each. Group I received no medications and served as a control group. Group II received for the full duration of the study a combination of aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Group III received the same regimen of platelet inhibition as in group II during the first 9 months, but were not treated during the subsequent 9-month interval. Grafts were excised for analysis from groups I and II at both 9 and 18 months and from group III at 18 months. Cholesterol content in group I grafts was 470 +/- 89 micrograms/100 mg at 9 months and 388 +/- 127 micrograms/100 mg at 18 months. In group II grafts, cholesterol content was 208 +/- 72 micrograms/100 mg at 9 months (p less than 0.001 compared with group I) and 266 +/- 84 micrograms/100 mg at 18 months. In group III grafts, cholesterol content was 249 +/- 71 micrograms/100 mg at 18 months. Differences in cholesterol content among the three groups of grafts at 18 months were not found to be statistically significant. Stepwise regression analysis at 18 months showed that cholesterol content was best predicted by medial fibrosis (r2 = 0.66) followed by abundance of foam cells (increase in r2 = 0.26) in group I, by fibrin in group II (r2 = 0.63), and by prevalence of macrophages in group III (r2 = 0.74). In all groups, platelets, fibrin, and polymorphonuclear leukocytes were less abundant than they had been at 3 months. Cross-sectional area occupied by the intima was not influenced by platelet inhibition.

Animals↗
PubMed1990

Intraluminal fibrosis and elastic fiber degradation lead to lung remodeling in pulmonary Langerhans cell granulomatosis (histiocytosis X).

To evaluate the morphogenesis of lung remodeling in pulmonary Langerhans cell granulomatosis (LCG; previously called histiocytosis X or eosinophilic granuloma), lung tissues obtained by open biopsy from 62 patients with pulmonary LCG were studied by light and electron microscopy. Tissues from 20 patients were also studied by immunohistochemical methods for the detection of fibronectin, elastin, and S-100 protein, and samples from six patients were studied using OKT6 monoclonal antibody. In early stages of pulmonary LCG, the epithelial lining cells were detached and Langerhans cells, inflammatory cells, and myofibroblasts migrated into intraluminal spaces through gaps in the epithelial basement membranes in and around the granulomatous lesions. In late stages, intraluminal fibrosis led to obstruction of alveolar spaces and airways and to coalescence of alveolar walls in and around the granulomatous lesions. Adjacent to these lesions, irregularly dilated alveoli were found with degraded and disrupted elastic fibers. Together, these observations suggest that intraluminal fibrosis and elastic fiber degradation are important processes of lung remodeling in pulmonary LCG.

Antibodies, Monoclonal↗
PubMed1989

Pathologic anatomy of the dilated cardiomyopathies.

Dilated cardiomyopathies are characterized by systolic pump failure and by dilatation of the ventricular cavity. Thus, they differ from the other 2 main types of cardiomyopathies, namely, hypertrophic cardiomyopathy and restrictive/obliterative cardiomyopathy. The term dilated cardiomyopathy designates a number of heterogeneous syndromes: idiopathic dilated cardiomyopathy, alcoholic cardiomyopathy, postpartal cardiomyopathy, infantile cardiomyopathy with histiocytoid change in cardiac muscle cells, anthracycline cardiomyopathy, Keshan disease, and several ultrastructurally distinct abnormalities, some of which maybe familial. The pathologic features of these syndromes are reviewed in detail.

Antibiotics, Antineoplastic↗
PubMed1989

Expression of the neutrophil elastase gene during human bone marrow cell differentiation.

Neutrophil elastase, a potent serine protease carried and released by activated neutrophils, is not synthesized by neutrophils, but by their bone marrow precursor cells. Using in situ hybridization with 35S-labeled antisense and sense neutrophil elastase cRNA probes, the present study demonstrates that expression of the neutrophil elastase gene is tightly controlled in bone marrow precursors and occurs during a very limited stage of differentiation of the neutrophil myeloid series, almost entirely at the promyelocyte stage. Neutrophil elastase mRNA transcript levels are detectable to a limited extent in blasts, increase markedly in the promyelocyte stage, and then disappear as promyelocytes further differentiate. Control probes specific for myeloperoxidase, lactoferrin, and beta-globin mRNA transcripts, respectively, demonstrated contrasting gene expression. Myeloperoxidase mRNA transcripts were also found almost exclusively at the promyelocyte stage, but myeloperoxidase mRNA levels disappeared earlier than do neutrophil elastase mRNA levels, suggesting that expression of these genes may be differently controlled. In comparison, lactoferrin mRNA transcripts were detected late in the neutrophil lineage, while beta-globin mRNA was detected only in cells of the erythroid lineage. Together these observations suggest that the expression of the neutrophil elastase gene is likely under very tight control, and is likely different than that for other constituents of the neutrophil granules.

Bone Marrow Cells↗
PubMed1989

Effects of ICRF-187 on the cardiac and renal toxicity of epirubicin in spontaneously hypertensive rats.

A study was made of the protective effect of ICRF-187 against the cardiotoxicity and nephrotoxicity produced by epirubicin in spontaneously hypertensive rats (SHR). A total of 20 SHR were divided into 4 groups of 5 animals; the first group received i.v. injections of 1.5 mg/kg epirubicin; the second was treated with i.p. injections of 50 mg/kg ICRF-187 30 min before receiving 1.5 mg/kg epirubicin; the two remaining groups received ICRF-187 and saline, respectively, and served as controls. The experiment was terminated after 12 weekly injections (total cumulative dose of epirubicin, 18 mg/kg). Morphologic studies showed that severe cardiomyopathy manifested by myofibrillar loss and dilatation of the sarcoplasmic reticulum and nephropathy characterized by tubular dilatation and atrophy, protein casts in the lumina of renal tubules, and glomerular vacuolization occurred in SHR given epirubicin alone. Animals receiving the combination of ICRF-187 and epirubicin showed a marked reduction in the severity of cardiomyopathy and a moderate reduction in nephropathy. These changes, and their modification by ICRF-187, were similar to those we have previously observed in SHR treated with total cumulative doses of 12 mg/kg doxorubicin. Such pathologic changes were absent in animals receiving ICRF-187 or saline alone. The findings of this study suggest that ICRF-187 can be used clinically to prevent the cardiotoxicity of epirubicin, particularly in situations in which this drug may have to be given either in large doses or to patients at high risk of developing anthracycline cardiotoxicity.

Animals↗
PubMed1989

Evolution of metaplastic squamous cells of alveolar walls in pulmonary fibrosis produced by paraquat. An ultrastructural and immunohistochemical study.

Sequential histologic, ultrastructural, immunohistochemical and morphometric studies were made of the evolutional changes of metaplastic and regenerating alveolar epithelial cells in monkeys from 3 days to 8 weeks after paraquat administration. In the early proliferative phase, many alveoli were lined by single-layered and stratified squamous epithelium and bronchiolized epithelium (i.e., presumably derived from bronchi and bronchioles). The regenerating epithelial cells had well developed bundles of actin-like filaments, which were arranged parallel to the basal surfaces of the cells and were associated with zonulae adherentes; these cells also had intermediate filaments and some desmosomes, but lacked basement membranes, hemidesmosomes and anchoring fibrils. They covered either denuded, wavy and disrupted original epithelial basement membranes or areas of developing intraalveolar fibrosis. In zones of squamous epithelial cell metaplasia associated with intraalveolar fibrosis, fibronexus-like structures appeared to be responsible for the initial adhesion of the cells to the underlying connective tissue. In later phases, single-layered and stratified squamous epithelial cells disappeared, and only bronchiolized epithelial cells, with hemidesmosomes and anchoring fibrils on their basal surfaces, were found in fibrotic alveoli. Although bronchiolized and squamous metaplastic epithelial cells are generally thought to be formed as late events in pulmonary damage, such cells play an important role in early, temporary repair of damaged alveoli.

Animals↗
PubMed1989

Morphogenesis of abnormal elastic fibers in lungs of patients with panacinar and centriacinar emphysema.

Pulmonary elastic fibers in a patient with panacinar emphysema due to alpha-1-antitrypsin deficiency and three patients with centriacinar emphysema related to anthracosis were studied by electron microscopy and by light and electron microscopic immunohistochemistry for elastin. Four types of abnormal elastic fibers were found: (1) finely disrupted fibers, (2) fibers with vacuolar changes and deposits of electron-dense granular material, (3) accumulations of small, rounded amorphous components of elastic fibers near bundles of microfibrils, and (4) large, confluent masses consisting mainly of aggregates of irregularly and compactly arranged, small-sized amorphous components. The amorphous components in these four types of abnormal elastic fibers tended to stain evenly with antielastin antibody. This is attributed to greater penetration of antielastin antibody into fibers that were incompletely polymerized because of immaturity or hydrolytic damage. Finely disrupted fibers were frequently found in the patient with panacinar emphysema and were presumed to have been damaged by elastase. The other three types of elastic fibers were frequently found in the patients with centriacinar emphysema. The vacuoles and electron-dense deposits in elastic fibers probably represented the consequence of damage to elastic fibers. The small round amorphous components in elastic fibers might be formed from abnormal elastogenesis. The large, confluent elastic masses were thought to be formed by the aggregation of elastic fibers in areas of coalescence of alveolar walls undergoing structural remodeling.

Adult↗
PubMed1989

Anticalcification treatments of bioprosthetic heart valves: in vivo studies in sheep.

Studies performed by other investigators have shown that a number of preimplantation processes inhibit the calcification of pieces of porcine aortic valves and of bovine parietal pericardium subcutaneously implanted in rats. To evaluate biological reactivity with these biomaterials functioning in an intracardiac position, mitral and tricuspid valve replacements were performed in young sheep to assess the effects of the following preimplantation processes: (1) surfactants, including sodium dodecyl sulfate, polysorbate-80, Triton X-100 and N-lauryl sarcosine; (2) covalently bound aminohydroxypropane diphosphonic acid; (3) toluidine blue; and (4) incorporation of polyacrylamide into valvular tissues. Quantitative calcium analyses showed that only the surfactants substantially reduced calcification, and only in porcine aortic valvular bioprostheses. However, morphological studies showed that some of these agents also induced alterations that decreased the durability of the valves. Toluidine blue decreased calcification to a degree that was statistically significant, but not biologically important. Polyacrylamide incorporation and diphosphonate binding increased calcification. Thus, data regarding anticalcification treatments obtained from subcutaneous implantation studies in small animal models should be cautiously interpreted and validated by studies with intracardiac valvular implantation in large animals.

Acrylic Resins↗
PubMed1989

Morphologic characterization of alveolar macrophages from subjects with occupational exposure to inorganic particles.

Alveolar macrophages recovered by bronchoalveolar lavage from 43 nonsmoking or greater than 5-yr ex-smoking subjects with occupational exposure to inorganic particles (asbestos, n 1/2 19; silica, n 1/2 10; coal, n 1/2 14) were evaluated by light microscopy and transmission and scanning electron microscopy to determine the morphologic changes resulting in these cells from chronic inorganic particulate inhalation. Alveolar macrophages from dust-exposed subjects, including those who had been free of exposure to particles for more than 1 yr, contained particles of higher proportion than did those of normal unexposed subjects. Most of these particles were located within phagolysosomes. The frequency of multinucleated alveolar macrophages was significantly higher in the dust-exposed groups. Ultrastructural studies showed alterations of the morphologic aspects of the surfaces of alveolar macrophages from the dust-exposed subjects, including increased numbers of rufflings, filopodia, pinocytotic vesicles, subplasmalemmal linear densities, and increased frequency of macrophage-macrophage and macrophage-lymphocyte interactions. Furthermore, the numbers of lysosomes were significantly increased in alveolar macrophages from the dust-exposed subjects. Together, these morphologic changes are consistent with the sequelae of phagocytosis, and they emphasize both the role of alveolar macrophages in eliminating inorganic particles from the alveolar spaces and the consequences this role has in alveolar macrophage activation.

Adult↗
PubMed1989

A comparative study of minoxidil-induced myocardial lesions in beagle dogs and miniature swine.

Minoxidil, a long-acting vasodilating antihypertensive agent, reduces arterial blood pressure by a direct action on arteriolar smooth muscle. The present studies examined the gross anatomic, histologic and ultrastructural myocardial alterations produced by 2 daily doses of minoxidil in beagle dogs (0.5, 1, or 3 mg/kg) and miniature swine (1, 3, or 10 mg/kg). Both myocardial necroses and hemorrhages were observed in dogs and pigs 24 hr after the last dose of minoxidil. In both species, the necroses were most frequent in the left ventricular papillary muscles, particularly the posterior one, but were less severe in swine. An ischemic origin of the necroses was suggested by the location of the lesions and by the pharmacologic effects of minoxidil. Gross epicardial or endocardial hemorrhages involving the atria and, to a lesser extent, the ventricles were observed in both species but were more severe in dogs. The atrial lesions were manifested grossly by diffuse redness and microscopically by interstitial edema, extravasated erythrocytes and infiltration of mononuclear cells. Hemorrhages, occurring on the epicardial surfaces, were often associated with lesions that involved small arteries having 3-6 layers of medial smooth muscle cells and were characterized by endothelial injury, intramural accumulations of erythrocytes and platelets, periadventitial hemorrhage, fibrin deposits and an inflammatory cell reaction. These lesions preferentially involved the right atrium in dogs and the left atrium in pigs. Pretreatment of beagle dogs with pyribenzamine (3 doses of 6 mg/kg every 8 hr), cimetidine (3 doses of 15 mg/kg every 8 hr), or both, had no effect on the incidence or severity of minoxidil-induced hemorrhagic lesions. The hemorrhagic lesions may be caused by overstretching of the vascular walls due to excessive, prolonged vasodilatation.

Animals↗
PubMed1989

Cardiac morphologic and functional changes induced by epirubicin chemotherapy.

Cardiac toxicity was evaluated in 24 patients who received epirubicin as a single chemotherapeutic agent, in doses of either 30 mg/m2 every week (11 patients) or 90 mg/m2 every 3 weeks (13 patients). The total doses of epirubicin ranged from 180 mg/m2 to 918 mg/m2 (mean, 491 +/- 187). No patient had prior heart disease, hypertension, mediastinal irradiation, or chemotherapy with other anthracycline agents. None of the patients developed overt heart failure, significant arrhythmias, ECG alterations, or roentgenographic changes in heart size. There was no significant change in the mean value of echocardiographic percent fractional shortening before and after epirubicin therapy. Patients receiving epirubicin doses less than 450 mg/m2 had minimal hemodynamic disturbances; however, no cut-off point separating two significantly different subpopulations could be demonstrated. Endomyocardial biopsy was performed on all patients; 20 biopsies were evaluable. Histologic and ultrastructural changes were similar to those caused by other anthracycline agents. A strong correlation was demonstrated between total dose of epirubicin and pathologic change as quantified using the Billingham scale (r = .7, P = .0006). A cut-off point beyond which there was a probability of increased pathologic damage was statistically defined at 450 mg/m2 of epirubicin. Severe pathologic alterations and moderate hemodynamic changes were observed in only one patient, who received 918 mg/m2 of epirubicin. Patients who are expected to receive epirubicin in excess of 450 mg/m2 should be monitored for cardiac toxicity, and continuation of epirubicin therapy beyond 900 mg/m2 should be based on the results of monitoring.

Adult↗
PubMed1988

Effect of pretreatment with ICRF-187 on the total cumulative dose of doxorubicin tolerated by beagle dogs.

Studies were made of the influence of ICRF-187 on the functional and morphological effects of very large cumulative doses of doxorubicin given over a prolonged period of time. Adult beagles of either sex (6.2-11.6 kg) were given doxorubicin (1.75 mg/kg i.v.) either alone or 15 min after ICRF-187 (25 mg/kg, i.v.) at 3-week intervals. Control dogs received ICRF-187 (25 mg/kg, i.v.) or 0.9% saline without doxorubicin. Of eight animals receiving doxorubicin alone, five died; two after a total dose of 12.25 mg/kg and three after 14 mg/kg; three others were in poor condition at the time of euthanasia after 14 mg/kg. Of eight animals receiving both ICRF-187 and doxorubicin, four died; two after 35 mg/kg, one after 43.75 mg/kg, and one after 52.5 mg/kg; two other dogs were euthanized after 43.75 mg/kg because of difficulties encountered in giving i.v. injections, and two dogs survived a total dose of 52.5 mg/kg. All control dogs survived. None of the treatment or control groups developed consistent echocardiographic changes or alterations in mean arterial pressure. By 300 days after onset of treatment, dogs given ICRF-187 and doxorubicin developed significant prolongation of the PQ interval; by 550 days, surviving dogs in this group developed ventricular premature contractions. Each animal receiving doxorubicin alone had severe myocardial lesions (lesion score 3+). Of the animals given ICRF-187 and doxorubicin, one that received 35 mg/kg doxorubicin had no lesions; of four given 43.75 mg/kg, three had no lesions and one had minimal lesions (lesion score 1+); of three given 52.5 mg/kg, one had minimal (lesion score 1+), and two had moderate (lesion score 2+) lesions. Control animals had no myocardial lesions. Thus, ICRF-187 provided significant protection when administered with doxorubicin over a period of 90 weeks, and made it possible to give doses of doxorubicin which otherwise would have been lethal.

Animals↗
PubMed1988

Demonstration by in situ hybridization of dissimilar IL-1 beta gene expression in human alveolar macrophages and blood monocytes in response to lipopolysaccharide.

IL-1 beta is the major form of IL-1 produced by mononuclear phagocytes. To evaluate the possible mechanisms underlying the observation that mature populations of human mononuclear phagocytes as alveolar macrophages are relatively poor IL-1 producers compared with blood monocytes, the expression of the IL-1 beta gene mRNA transcripts was evaluated in LPS-stimulated normal autologous blood monocytes and alveolar macrophages by using a IL-1 beta cDNA probe. Although Northern analysis demonstrated that stimulated monocytes and alveolar macrophages both express 1.8-kb IL-1 beta mRNA transcripts, cytoplasmic dot blot analysis showed that the total IL-1 beta mRNA content in alveolar macrophages was only 38 +/- 5% of that in blood monocytes. In situ hybridization with antisense and sense IL-1 beta RNA probes demonstrated that whereas most of stimulated blood monocytes contained IL-1 beta mRNA transcripts, a significant proportion of autologous alveolar macrophages stimulated in an identical fashion did not express the IL-1 beta gene. Within 4 h after LPS stimulation, IL-1 beta mRNA transcripts were detected in 81 +/- 6% monocytes, whereas only 16 +/- 9% of alveolar macrophages were positive, and by 18 h this had increased only to 43 +/- 15%. Quantification of the size distribution of the IL-1 beta mRNA expressing mononuclear phagocytes demonstrated that, among the population of alveolar macrophages, the cells expressing this gene were not confined to those that were "monocyte-like." These observations demonstrate that there is a heterogeneity among population of mononuclear phagocytes in their ability to express the gene for IL-1 beta, which could explain the differences observed in IL-1 production.

Gene Expression Regulation↗
PubMed1988

Influence of minoxidil on myocardial hemodynamics, regional blood flow, and morphology in beagle dogs.

Studies were made of the effects of two doses of minoxidil (3 mg/kg), given 24 hours apart, on cardiovascular hemodynamics, regional myocardial blood flow, and cardiac morphology in beagle dogs. Minoxidil caused increases in mean right atrial and left ventricular end-diastolic pressure. Systemic and pulmonary vascular resistance were reduced; cardiac output was increased. Left ventricular stroke work and the systolic pressure time index were unchanged by monoxidil administration. The diastolic pressure time index and ratio of diastolic/systolic pressure time index were decreased by minoxidil. Regional myocardial blood flow, measured with radioactive microspheres, increased in all regions of the heart except to the left ventricular papillary muscles. Minoxidil increased blood flow to left ventricular subendocardial tissue; however, this increase was significantly less than that observed in corresponding areas of subepicardial tissue, thus reducing the subendocardial/subepicardial tissue blood flow ratio. These results suggest that minoxidil is an effective peripheral vasodilator but may result in inadequate subendocardial perfusion. Morphologic studies disclosed two types of minoxidil-induced cardiac lesions: left ventricular papillary muscle necroses, and hemorrhagic lesions which were most prominent in right atrium and were associated with inflammation, intramural hemorrhage, and fibrinoid necrosis of small arteries. The papillary muscle necrosis were attributed to hypoxia. The atrial lesions were not of ischemic or hypoxic origin, because minoxidil did not decrease blood flow to atrial tissue. It is suggested that the atrial lesions are related to excessive vasodilation.

Animals↗