PubMed Health⌕ Search

Biomedical subjects

R Ferrera

Publications and source records attributed to R Ferrera.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of chronic oral supplementation with alpha-tocopherol on myocardial stunning in the dog.

Recent clinical and experimental studies have suggested that antioxidant supplements might actually have harmful as well as beneficial effects in the setting of cardiovascular disease. The mechanisms underlying the beneficial effects of the various antioxidants are poorly understood in humans. Reperfusion-associated myocardial injury, and particularly the phenomenon of stunning, is important because it occurs in clinical settings and may condition the prognosis after short ischemic insult. We studied the effects of chronic (3 months) alpha-tocopherol supplementation with a large oral dose (500 mg daily) on myocardial contractility (stunning) and ventricular arrhythmias in a dog model of short ischemia followed by reperfusion. Twenty dogs were randomized to either an alpha-tocopherol supplemented or a control group. After 3 months, dogs were anesthetized and underwent a 20-min coronary artery occlusion followed by reperfusion. Myocardial regional blood flow was measured by the radioactive microsphere technique and myocardial contractility by sonomicrometry. Plasma alpha-tocopherol was measured by high-performance liquid chromatography in all dogs. Twelve dogs (seven supplemented and five controls) developed ventricular fibrillation at reperfusion, showing no difference between groups. Hemodynamic parameters, blood flow in the ischemic area (collateral flow), and area at risk were similar in the two groups. Regional systolic segment shortening in the ischemic area was similar during ischemia and reperfusion in both groups, representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and 51 +/- 8% in supplemented dogs after 150 min of reperfusion. Plasma alpha-tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and 6.9 +/- 0.6 mg/L; p < 0.001). Thus a long-term large dose of alpha-tocopherol had no significant effect on postischaemic ventricular arrhythmias and dysfunction (myocardial stunning) in this canine model. These data suggest that if alpha-tocopherol supplementation might be useful to improve the prognosis of coronary patients, it is likely not by interfering with the stunning phenomenon.

Administration, Oral↗
PubMed1997

[Brain death: myocardial consequences, an experimental study on pigs].

It is well known that brain death is responsible for major problems encountered in the clinical setting that may alter heart graft viability before transplantation. To investigate these myocardial dysfunctions, a model of brain death was prepared in pigs. Anaesthetised pigs were ventilated with FiO2 of 50% through an endotracheal tube. Animals were monitored by measuring systemic arterial pressure, pulmonary artery pressure, cardiac output, left ventricular developed pressure and dP/dT (Millar probe), cardiac contractility (sonomicrometers crystals), ECG, myocardial tissue oedema (impedance spectroscopy) and heart rate. Blood samples were drawn to assess arterial blood gases, serum electrolytes, plasma catecholamine levels, LDH isoenzymes and ascorbil free radicals production. Myocardial high energy contents (adenosine triphosphate, creatine phosphate) were measured by spectroscopy MRI. After 30 minutes stabilisation, brain death was induced by ligation of the supra-aortic vessels. To assess myocardial impairment all the parameters mentioned were recorded at baseline, 1', 30', 60', 120' and 180' following the brain death. Results showed initial tachycardia and a significant increase (p < 0.05) in cardiac function at 1' and 30', related to the cathecolamine level variations, followed by a significant depression (p < 0.05) of cardiac contractility by the end of the third hour; there was no modification whatsoever of myocardial high energy contents and of ascorbil free radical and LDH isoenzymes productions. In this pig model of brain death the observed myocardial dysfunction was directly related to the induced catecholamine secretion without any myocardial high energy substrate depletion up until 180'. Such results could be taken into account when evaluating a donor heart, allowing to use organs judged nowadays not feasible, and could be of some help in lowering the number of the "défaillances" of the transplanted hearts.

Animals↗
PubMed1996

High prevalence of thromoembolic complications in heart transplant recipients. Which preventive strategy.?

Consecutive patients transplanted between January 1984 and December 1988 were followed until August 1992 to detect fatal and nonfatal thromboembolic complications, including sudden death, acute and chronic myocardial infarction, pulmonary and peripheral embolisms, stroke, and thrombophlebitis. The probability of developing such complications was 9.86 per 100 patients per year. The probability of fatal complications was 3.97% per year; the mean interval between transplant and death was 1247 days versus 29.5 days for nonthromboembolic deaths. Thromboembolic deaths represented 5.1% of total mortality at the first year posttransplant but 57, 30, 67 and 73% at the second, third, fourth, and fifth years, respectively. Among the prognosis factors that were analyzed, none was significant predictor of thromboembolic complication. This high prevalence of thromboembolic complications suggests that effective antithrombotic strategy should be defined in heart transplant recipients.

Adolescent↗
PubMed1996

Effect of colchicine on circulating and myocardial neutrophils and on infarct size in a canine model of ischemia and reperfusion.

Myocardial injury after ischemia/reperfusion has been attributed in part to the effects of neutrophils. We examined whether colchicine, a potent and rapid inhibitor of neutrophils, may reduce inflammatory leukocytosis, prevent postischemic myocardial neutrophil accumulation, and reduce infarct size (IS). Twenty-four dogs were randomized to either a control (saline administration) or a colchicine (1 mg/kg intravenously, i.v.) group. Anesthetized open-chest dogs underwent 120-min coronary artery occlusion followed by 6-h reperfusion. Determinants of IS [area-at-risk (AAR) and collateral flow] and IS were measured in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex vivo production of reactive oxygen species by chemiluminescence. Myocardial localization and accumulation of neutrophils were histologically evaluated by independent observers. The number of circulating neutrophils (p < 0.01), neutrophil cytotoxicity (p < 0.05), and neutrophil myocardial accumulation after 6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV) peak rate of pressure increase was similar in both groups during ischemia /reperfusion. However, whereas collateral blood flow and AAR, the main determinants of IS, were similar in control and treated dogs, there was no reduction in IS: 37.1 +/- 7% of AAR in controls and 37.4 +/- 8% in treated dogs. Despite marked reduction of neutrophil toxicity and postischemic myocardial neutrophil accumulation, no myocardial protection could be detected in this dog model.

Animals↗
PubMed1996

Effect of trimetazidine on postischemic regional myocardial stunning in the halothane-anesthetized dog.

Trimetazidine (TMZ) has been described as a new antiischemic agent. Whereas its precise mechanism of action remains unknown, antioxidant properties and the ability to preserve high-energy phosphate metabolism have been reported. Accordingly, we studied whether TMZ may limit postischemic regional myocardial stunning (known to be caused by reactive oxygen species) and influence recruitment of contractile reserve by inotropic stimulation in a dog model, using halothane to maintain steady anesthesia throughout the experiment. Dogs were submitted to a 15-min coronary artery occlusion followed by reperfusion. The blinded protocol included a 3-day oral pretreatment (1 mg/kg/day), a bolus injection (0.5 mg/kg), followed by intravenous infusion (0.5 mg/h) initiated 15 min before coronary artery occlusion. Despite lower heart rate (HR) and significant reduction of lipid peroxidation in treated dogs, myocardial stunning and recruitment of contractile reserve by dobutamine infusion in the postischemic myocardium were not modified by TMZ. Adenine nucleotide pool in the postischemic myocardium was considerably reduced as compared with the nonischemic myocardium in both groups. Therefore, in halothane-anesthetized dogs, the antioxidant properties of TMZ were not sufficient to protect myocardium in terms of postischemic dysfunction after 15-min ischemia.

Adenine Nucleotides↗
PubMed1995

Importance of initial coronary artery flow after heart procurement to assess heart viability before transplantation.

BACKGROUND: The objective of this study was to evaluate different tests of heart viability in a pig model of warm ischemia. METHODS AND RESULTS: Pig hearts (n = 30) were submitted to 0 (= group I), 10 (group II), 20 (group III), 30 (group IV), and 60 (group V) minutes of in situ warm ischemia (animal exsanguination). Hearts were removed, then flushed with cardioplegic solution for 3 minutes at a fixed pressure of 60 cm H2O, and edema formation, initial coronary flow, and ionic composition (Na+, K+, and Ca++) of coronary sinus effluent were evaluated. Hearts were then stored for 2 hours in a cold (4 degrees C) preservation solution. Myocardial biopsies (and evaluation of energetic index) were performed, then the hearts were reperfused for 30 minutes with whole blood with an in vitro functional testing system. No edema occurred during cardioplegic flush in the hearts in groups I through IV, but a 37 +/- 11% weight increase (P < .001) occurred in hearts in group V. There was a progressive decrease in initial coronary flow with the increase in the duration of warm ischemia (70 +/- 14 mL/min per 100 g of tissue in group I and 52 +/- 9, 41 +/- 16, 25 +/- 11, and 23 +/- 5 mL/min per 100 g, respectively, in groups II through V (P < .01 to P < .001 versus group I). Initial coronary flow was positively correlated with the energetic index (r = .84, P < .001), and the left ventricle developed pressure at reperfusion (r = .90, P < .001). Finally, there were significant differences between hearts in the control group and those in group V for calcium and sodium release (lower in the control group; P < .001 and P < .01, respectively) and for potassium removal (lower in group V, P < .05). CONCLUSIONS: These data suggest that early measurement of coronary flow after removal of the heart may help to assess heart viability before transplantation. This approach may provide a comprehensive clinical evaluation to increase the number of hearts available for transplantation among those that are rejected in the absence of accurate criteria of viability.

Animals↗
PubMed1994

The beneficial effect of dietary antioxidant supplementation on platelet aggregation and cyclosporine treatment in heart transplant recipients.

To determine whether dietary antioxidant supplementation can reduce platelet reactivity in heart transplant recipients, 20 patients were prospectively randomized to receive either 500 IU vitamin E orally per day in the form of acetate for 2 months or no vitamin E. Blood creatinine (P = 0.01) and lymphocyte count (P = 0.009) significantly decreased only in supplemented patients, whereas the cyclosporine blood level was not modified. Platelet aggregation was stable in control patients but significantly decreased in supplemented patients in response to either thrombin (from 8.3 +/- 0.9% of maximum aggregation to 3.7 +/- 0.7, P = 0.001) or ADP (secondary wave: from 44.7 +/- 5.9% to 33.2 +/- 7.0, P = 0.02). Thus antioxidant supplementation tended to improve immunosuppression (by reducing lymphocyte count), to reduce cyclosporine nephrotoxicity, and to decrease the high thrombotic risk associated with heart transplantation.

Administration, Oral↗
PubMed1994

Comparison of different techniques of hypothermic pig heart preservation.

The aim of this study was to compare several methods of hypothermic heart preservation. Isolated pig hearts were preserved for 24 hours in cold cardioplegic solution (St. Thomas' Hospital modified solution) by continuous perfusion (group I), microperfusion (group II), or simple storage (group III). The findings were then compared with those from hearts harvested and immediately reperfused (the control group). Group III hearts showed lower adenosine triphosphate preservation (0.47 +/- 0.18 mumol/g) than did group I and II hearts and the control hearts (1.86 +/- 0.40, 1.98 +/- 0.27, and 1.84 +/- 0.55 mumol/kg, respectively). Electronic microscopy studies also revealed that the myocardial cells in the group III hearts appeared to be damaged. After the hearts had undergone preservation, myocardial function was studied for 60 minutes under nonworking conditions using an ex vivo functional testing system. For group III, the mean left ventricular developed pressure and ventricular compliance (16 +/- 22 and 63 +/- 48 mm Hg, respectively) differed significantly from those for group I (83 +/- 26 and 0 +/- 0 mm Hg, respectively), group II (83 +/- 33 and 14 +/- 18 mm Hg, respectively), and the control group (115 +/- 13 and 0 +/- 0 mm Hg, respectively). We concluded from our findings that perfusion methods are superior to cold storage but inadequate to maintain heart viability for the long term during hypothermia. These techniques must be improved before they can be adopted for clinical use.

Adenine Nucleotides↗
PubMed1993

Quantitative reduction of MTT by hearts biopsies in vitro is an index of viability.

The aim of this study is to evaluate the use of tetrazolium reductase (TR) activity as an indicator of myocardial viability in an isolated arrested pig heart biopsy model. Methyl Tetrazolium (MTT) is cleaved by an enzyme in the presence of coenzymes NAD, NADP. Cleavage yields a highly colored formazan product which is DMSO soluble. Efficient bioreduction of MTT has been investigated with heart biopsies. The relationship between MTT reduction and (1) oxygen consumption (r = 0.96, P < 0.001), (2) the sum of the adenine nucleotide levels (r = 0.87, P < 0.001) and (3) localization of coloration, has been established. The use of MTT in colorimetric assays offers high sensitivity. MTT reduction is a valid method. It is rapid and reproducible, and can be used as an indicator of myocardial viability. The MTT test has been used to rapidly compare the effect of different cardioplegic solutions (St Thomas and improved St Thomas) on hypothermic cardiac preservation. Significant differences have been established between the two solutions (P < 0.01).

Adenine Nucleotides↗
PubMed1984

Effect of varying amounts of ascorbate on collagen, elastin and lysyl oxidase synthesis in aortic smooth muscle cell cultures.

In the presence of ascorbate, there is an increase in collagen synthesis with a concomitant decrease in insoluble elastin and lysyl oxidase activity in cultured rabbit aortic smooth muscle cells. While the addition of 0.5 micrograms ascorbate per ml of medium enhances collagen synthesis and accumulation, detectable insoluble elastin and lysyl oxidase activity remain essentially unchanged. However, at 2 micrograms ascorbate per ml, the integrity of the insoluble elastin is lost and lysyl oxidase activity is decreased. These studies suggest that by modifying the levels of ascorbate in the culture medium one can alter the nature of the extracellular matrix produced by the smooth muscle cells.

Amino Acid Oxidoreductases↗
PubMed1984

Mammalian cell growth on collagen-hydrogels.

Hydroxyethylmethacrylate (HEMA) hydrogels have a peculiar crater-like topography which renders them ideal for studying cell-to-substrate contact formation. Cultured rabbit aortic smooth muscle cells (SMC) were grown on collagen-HEMA hydrogels, and the ultrastructure of developing cell attachment sites was studied. By 3 hours after cell seeding, both the rounded and spreading SMC appeared anchored to the hydrogel via extra-cellular connective tissue-like material. The fully formed attachment site present at 5-8 day was characterized by large bundles of intracellular myofilaments inserting onto areas of increased electron density along the plasmalemmal membrane. Large amounts of extracellular connective tissue-like material also appeared attached to the areas of increased electron density. Fully formed cell substratum attachment sites were not observed when either elastin-HEMA or hydrogels polymerized in the absence of protein were employed. The growth and collagen synthesis by human embryonic lung fibroblasts (IMR-90) and endothelial cells on collagen-HEMA hydrogels and tissue culture plastic were also examined. Although the two cell types grew equally well on the two surfaces, differences in protein synthesis were observed. The procollagen Type I and III ratio synthesized by the fibroblasts remained the same while the ratio synthesized by the endothelial cells varied even though their morphology appeared similar. The fibroblasts synthesized less collagen when grown on collagen-HEMA hydrogels (this effect may be related to age), while the amount of collagen synthesized by the endothelial cells grown on the two surfaces was similar.

Animals↗
PubMed1983

Effect of protein-hydroxyethylmethacrylate hydrogels on cultured endothelial cells.

The use of protein hydroxy ethylmethacrylate (HEMA) hydrogels to control cell morphology and growth, as well as the synthesis of extracellular matrix components, is described in this communication. HEMA hydrogels prepared with collagen support growth of embryonic lung fibroblasts (IMR-90), as well as bovine aortic and pulmonary artery endothelial cells at a level comparable to the respective cells grown on tissue culture surfaces. On the other hand, HEMA hydrogels prepared with solubilized elastin inhibit the fibroblast growth and prevent both types of endothelial cell cultures from achieving their normal morphology. These morphologically altered endothelial cells resume a normal cobblestone-like appearance when subcultivated from the elastin-HEMA hydrogels to tissue culture plastic. When pulsed with [14C]proline, the procollagens synthesized by the endothelial cells on the different surfaces vary, as shown by immunoprecipitation and polyacrylamide gel electrophoresis. On the standard tissue culture plastic, the confluent cells produce mainly type III procollagen in the medium, whereas those endothelial cells grown on collagen and elastin-HEMA hydrogels synthesize primarily type I procollagen (much like sprouting cells on tissue culture plastic), regardless of their morphology.

Acrylates↗
PubMed1981

Measurement of medium lysyl oxidase activity in aorta smooth muscle cells. Effects of multiple medium changes and inhibition of protein synthesis.

Cultures of rabbit aortic smooth muscle (RSM) cells are a valuable model system for studying production and metabolism of connective tissue components. This report describes various assay procedures for lysyl oxidase, the enzyme responsible for deaminating lysine residues to give aldehyde cross-link precursors, in culture medium from these cells. Studies of the medium enzyme from second-passage RSM cells indicate that approximately 40% of the total enzyme activity in the flask of cells is in the medium. The medium enzyme levels are replenished quite rapidly following refeeding, and enzyme levels in the medium appear to be feedback controlled. The mechanism for this control is unknown at present. Multiple refeeding experiments in which the medium was changed every 2-4 h for up to 40 h indicate that these cells are cap]able of producing large amounts of enzyme and are capable of altering enzyme production and secretion quite rapidly in response to changes in their environment. Protein synthesis inhibitor studies with cycloheximide suggest that the major portion of the enzyme released into the medium following refeeding is newly synthesized although a pool of latent enzyme is also present. As in intact tissue, extraction of the enzyme from the cell layer requires strong denaturing reagents such as 4 M urea. These results suggest that the production of lysyl oxidase is closely regulated and is very responsive to changes in the external environment of the cells. This cell culture system appears to be an excellent one to study the production of lysyl oxidase and its role in connective tissue fibrillogenesis.

Amino Acid Oxidoreductases↗