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Biomedical subjects

G Rousseau

Publications and source records attributed to G Rousseau.

At least 19 recordsLinked to original sources
PubMed1996

Distinct receptor domains determine subtype-specific coupling and desensitization phenotypes for human beta1- and beta2-adrenergic receptors.

Human beta1- and beta2-adrenergic receptor (beta1 AR and beta2 AR) coupling and desensitization characteristics were compared in defined heterologous expression systems. Significant differences in the coupling efficacies of the two subtypes were found in both Chinese hamster fibroblasts and murine Ltk- fibroblasts, which were used as surrogate cell lines. At the maximal level of stimulation with the nonselective beta-adrenergic agonist isoproterenol, beta1 AR-mediated adenylyl cyclase activation represented 70% and 20% of that mediated by beta2 AR in Chinese hamster and murine Ltk- fibroblasts, respectively. Sustained (15 min) stimulation with subsaturating concentration of isoproterenol (< 10% of receptor occupancy) led to identical desensitization of the beta-adrenergic-stimulated adenylyl cyclase activity for both beta1 AR and beta2AR-expressing cells. In contrast, when a nearly saturating concentration of isoproterenol (> 90% of receptor occupancy) was used to promote desensitization, the extent of desensitization observed for beta2 AR-expressing cells was 1.7-2-fold higher than that of the beta1 AR. The carboxyl domain of several G protein-coupled receptors has been shown to play important roles in both coupling efficacy and agonist-promoted desensitization. Therefore, we examined the contribution of this receptor domain in the subtype-selective phenotypes described above. A chimeric receptor composed of the first six transmembrane domains of the beta1 AR and of the seventh transmembrane domain and carboxyl tail of the beta2 AR maintained a coupling efficacy characteristic of the beta1 AR, whereas the extent of desensitization resulting from high receptor occupancy was identical to that of the beta2 AR. These results therefore suggest that the carboxyl portion of the beta1 AR and beta2 AR determines their subtype-selective desensitization patterns but not their respective coupling efficacies.

Adenylyl Cyclases↗
PubMed1994

Clentiazem given at reperfusion improves subendocardial reflow and reduces myocardial infarct size in the dog.

The postischemic cardioprotection by calcium antagonists and the interplay between neutrophils and regional myocardial blood flow were investigated further, using clentiazem, a new potent calcium channel blocker derived from diltiazem. A 90-min occlusion of the interventricular coronary artery was followed by 6 hr of reperfusion in anesthetized dogs. One group was given clentiazem: 100 micrograms/kg at 5 min before reperfusion followed by a perfusion of 1 microgram/kg/min until sacrifice; controls received saline. Infarct size (% of area at risk) estimated with triphenyltetrazolium staining and by histology was reduced by nearly 50% (P < .05) in treated (16.6 +/- 3.0%), as compared to control (31.6 +/- 6.3%) dogs. Regional and collateral myocardial flows estimated with radioactive microspheres were similar between groups before and during occlusion. However, after an initial recovery to preocclusion values at 30-min reperfusion in both groups, flow declined to 50% normal (P < .05) in control animals after 3 and 6 hr in midwall and subendocardium, but the change was remarkably attenuated (P < .05) in subendocardium of clentiazem-treated dogs. Also, neutrophil accumulation at the epicardial side of the infarct, at the edge of salvaged myocardium, and estimated by tissue myeloperoxidase measurement, was reduced by 50% in treated dogs (clentiazem: 17.2 +/- 2.8; controls: 32.3 +/- 2.7 x 10(6) neutrophils/g). We conclude that administration of clentiazem at reperfusion reduces infarct size by interfering with both neutrophil accumulation and development of subendocardial no reflow in reperfused myocardium.

Animals↗
PubMed1993

Similarity of primary radical pair recombination in photosystem II and bacterial reaction centers.

We report temperature and magnetic field dependent measurements of the recombination dynamics of the radical pair P680+Pheo- in D1D2cytb559 reaction centers of photosystem II and compare the results to those obtained in bacterial reaction centers. In photosystem II the rate of recombination to the groundstate is found to be slower than in the bacterial reaction centers by a factor of at least 50. This difference arises from the different redox potentials of the pigments of plant and bacterial reaction centers. In contrast, the rate of recombination to the triplet state is similar in all reaction centers, indicating a similar electronic coupling which allows us to conclude upon the structural similarity.

Chlorophyll↗
PubMed1993

Importance of platelets in myocardial injury after reperfusion in the presence of residual coronary stenosis in dogs.

Residual coronary stenosis is common after successful thrombolysis for acute infarction. We investigated the role of platelets and the influence of a residual critical stenosis during early reperfusion in survival of reperfused myocardium. The left anterior descending coronary artery was occluded for 90 minutes and reperfused for 6 hours in 5 groups of dogs, 3 with a residual critical stenosis (groups 1 through 3) and 2 without (groups 4 and 5). Thrombocytopenia was produced by an antiserum in groups 2, 3, and 5; group 3 was also made neutropenic by another antiserum. Platelets (groups 1 and 4) and neutrophils (groups 1, 2, 4, and 5) labeled with indium 111 were reinjected at occlusion. Collateral flow was estimated with radioactive microspheres and was statistically similar among groups. Infarct size (percentage of area at risk), revealed by triphenyltetrazolium, was more severe (49.4% +/- 4.0%; p < 0.05) with stenosis (group 1) than without stenosis (group 4: 29.5% +/- 4.6%). Platelet depletion reduced infarct size in group 2 (28.6% +/- 6.3%; p < 0.05 vs group 1) with stenosis, but not in group 5 without stenosis (24.5% +/- 6.2% vs group 4: 29.5% +/- 4.6%). Neutropenia (group 3) did not decrease infarct size in thrombocytopenic dogs. Neutrophil accumulations in reperfused myocardium were similar among groups, but platelets accumulated in greater numbers in reperfused infarcts with stenosis (group 1: 338,581 +/- 52,857/gm; p < 0.05) than without stenosis (group 4: 153,445 +/- 23,949/gm). Therefore a critical stenosis at reperfusion compromises myocardial salvage and increases infarct size by means of a platelet-mediated mechanism.

Animals↗
PubMed1993

Sustained myocardial protection by clentiazem (TA-3090) after a 90-minute coronary occlusion and 72 hours of reperfusion in dogs with collateral flow.

Reduction of infarct size by calcium channel blockers, given at reperfusion, has been reported with diltiazem and clentiazem after 6 h of reperfusion following a 90-min coronary occlusion in the dog. The aims of the present study were to establish that the postischemic cardioprotection is not simply a delay in cell death, but a sustained or permanent myocardial salvage. Dogs with a 90-min occlusion of the left descending coronary artery underwent reperfusion for 72 h. Five minutes before reperfusion, they received, at random, i.v. saline (controls) or clentiazem (125 micrograms/kg i.v.), followed by infusion of 1 microgram/kg/min, until sacrifice. Transmural collateral flow measured 15 min after occlusion with radioactive microspheres was not statistically different between groups [(means +/- SE) control: 0.123 +/- 0.040; treated: 0.150 +/- 0.042 ml/min/g]. The area at risk (percentage of left ventricle), delimited by Evans blue perfusion was also similar (control: 39.9 +/- 1.5%; treated: 42.4 +/- 1.6%). Infarct size, estimated as percentage of the area at risk by triphenyltetrazolium chloride and histology, was reduced (p < 0.05) in treated dogs (control, 42.4 +/- 4.7%; treated, 26.5 +/- 5.4%) with collateral flow (> 0.02 ml/min/g), but not in those with virtually no (< 0.02 ml/min/g) collateral flow (control, 62.0 +/- 8.9%; treated, 72.7 +/- 6.8%). Therefore clentiazem, at reperfusion after a 90-min ischemia, increases myocardial salvage limiting postischemic injury and providing sustained reduction of infarct size in dogs with collateral blood flow.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Effect of coronary reperfusion on technetium-99m methoxyisobutylisonitrile uptake by viable and necrotic myocardium in the dog.

Technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) distribution is flow-dependent, permitting the imaging of coronary perfusion defects. However, the behaviour of this tracer in viable and necrotic tissues within the ischaemic area at risk is still being debated. In a clinically relevant canine model, dogs were submitted either to a 24-h permanent occlusion (group 1) of the left descending coronary artery (LAD) or to a 90-min LAD occlusion followed by 22.5 h reperfusion (group 2). 99mTc-MIBI and radiolabelled microspheres were injected 3 h before sacrifice. After delimiting the area at risk and the infarct by Evans blue perfusion and triphenyltetrazolium chloride staining, heart slices were imaged by scintigraphy and tissue radioactivity measured in a gamma-counter. In the necrotic area of both groups, the 99mTc-MIBI distribution was proportional to the myocardial blood flow, approximating a 1:1 ratio (identity line slope 1, intercept 0) with highly significant correlation coefficients (group 1 r = 0.87, group 2 r = 0.86), whereas in the viable-ischaemic area of both groups, the data points are widespread above and below the identity line, indicating both over- and underestimations of blood flow in these tissue areas. These results were more pronounced following reperfusion as compared with permanent occlusion. Multiple linear regression analysis confirms differences (P less than 0.001) in 99mTc-MIBI distributions between the viable-ischaemic and the necrotic zones. Delineation of the ischaemic area at risk was possible only with permanent occlusion. A hypoperfused area was observed after reperfusion but differs from the anatomical infarcted area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The gene for tissue inhibitor of metalloproteinases-2 is localized on human chromosome arm 17q25.

Tissue inhibitor of metalloproteinases-2 (TIMP2) is a natural inhibitor of several proteinases that are involved in the degradation of the extracellular matrix. By means of somatic cell hybrids segregating human chromosomes, the gene encoding this inhibitor was assigned to human chromosome 17. Fluorescence in situ hybridization confirmed this assignment and allowed mapping of the gene to the terminal region (17q25) of the chromosome.

Animals↗
PubMed1991

Diltiazem at reperfusion reduces neutrophil accumulation and infarct size in dogs with ischaemic myocardium.

STUDY OBJECTIVE: The aim was to demonstrate the ability of diltiazem to protect the ischaemic myocardium in the course of coronary reperfusion, and to establish if an interaction with neutrophils is implied. DESIGN: Ischaemia was induced by occluding the left anterior descending coronary artery for 90 min followed by 6 h of reperfusion with a residual critical stenosis left in place. Three groups were studied: group 1 (control) received a saline perfusion; group 2 was given a bolus injection of 400 micrograms.kg-1 of diltiazem 10 min before reperfusion, followed by 4 micrograms.kg-1.min-1 perfusion until termination of experiment; group 3 was made neutropenic by injecting a neutrophil antiserum produced in rabbits and was then treated with diltiazem, as in the second group. SUBJECTS: 60 mongrel dogs of either sex were allocated at random into one of the three groups the day before the experiment. MEASUREMENTS AND MAIN RESULTS: Diltiazem plasma concentrations ranged from 68.6(SEM 10.0) to 102.5(15.2) micrograms.litre-1 during the study. Transmural collateral blood flow, measured with 153Gd microspheres 15 min after occlusion, and area at risk, evaluated by Evans blue perfusion, did not differ among the three groups. Infarct size, estimated by triphenyltetrazolium staining of heart slices and expressed as a percentage of area at risk, was less (p less than 0.05) in the diltiazem [20.5(5.2)%] and diltiazem plus neutropenia [17.6(5.4)%] groups compared to controls [39.8(6.9)%] but neutropenia added no significant benefit to diltiazem alone. The animals treated with diltiazem alone had lower serum creatine kinase levels than controls, at 5719(891) v 14,333(2885) IU.litre-1, p less than 0.05. The neutrophilia seen in controls was virtually absent in diltiazem dogs. Myocardial neutrophil accumulation estimated by scintigraphy of 111In labelled autologous neutrophils was much less in diltiazem than in control dogs, at 3948(1228) v 11,021(2081) 111In-neutrophil.g-1 of infarct, p less than 0.02. CONCLUSIONS: Diltiazem given during reperfusion reduces infarct size by a mechanism that includes an inhibition of neutrophil accumulation in the post-ischaemic myocardium.

Animals↗
PubMed1991

Effect of beta-estradiol on production of the cell-detaching factor of Trichomonas vaginalis.

Despite over 40 years of study, the pathogenetic mechanisms of Trichomonas vaginalis are just starting to be elucidated. We have recently reported that T. vaginalis produces a virulence factor, cell-detaching factor (CDF), that likely causes the cell sloughing seen in clinical disease. This 200-kDa glycoprotein is acid and heat labile and correlates with clinical symptoms. We applied a McCoy cell culture system to study the effects of various concentrations of beta-estradiol (10(-6) to 10(-10) M) on T. vaginalis growth and CDF production. T. vaginalis growth was unaffected by the different concentrations of beta-estradiol studied, in comparison with the growth of control cultures without beta-estradiol. However, beta-estradiol significantly diminished the activity of CDF at all concentrations and did so most profoundly at 10(-7) and 10(-8) M (P less than 0.0001). This suggests that the symptoms of T. vaginalis infection may be influenced by the vaginal concentration of estrogens, and further studies of the interactions between T. vaginalis and estrogens are warranted.

Animals↗
PubMed1991

[Control of growth hormone synthesis, paradigm of tissue specificity and of hormonal gene expression regulation].

The study of the transcriptional control of the growth hormone gene illustrates the complementary role of three types of regulatory proteins. These proteins bind to the gene upstream of the transcription initiation site to stimulate or inhibit transcription. A first type of proteins includes ubiquitous factors. A second type includes receptors for hormones that act in the nucleus. A third type is represented by the pituitary factor Pit-1, the prototype of a novel class of proteins that are also involved in controlling embryonic development and cell proliferation. Indeed, Pit-1 determines not only the tissue specificity of expression of the growth hormone gene, but also its control by somatocrinin, as well as the ontogeny of the anterior pituitary and the maintenance of the differentiated phenotype.

DNA-Binding Proteins↗
PubMed1991

[Abdominal pregnancy. An autochtonous case with full-term living normal infant].

Abdominal pregnancy is a serious obstetrical dilemma for mother and baby. Exceptional in the western world, it's often unsuspected or lately diagnosed. We report an autochtonous case, discovered at operation, with an alive, normal and full-term baby, and dramatic hemorrhagic consequences, threatening the mother's life.

Blood Transfusion↗
PubMed1990

Influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a canine preparation of myocardial infarction.

STUDY OBJECTIVE - The aim of the study was to investigate the influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a model of myocardial ischaemia. DESIGN - Myocardial ischaemia was induced in an open chest canine model by occluding the left coronary artery for 2 h. This was followed by 6 h reperfusion. The influence of reflow fibrillation and internal electric defibrillation on infarct size was investigated and compared to dogs which did not develop fibrillation. Infarct size and its major determinants, rate-pressure product (RPP), area at risk (AR), and collateral flow (MBF), were measured and their relationships studied in the two situations, using uni- and multilinear regression analysis. SUBJECTS - 21 adult mongrel dogs of either sex were used in the studies, which were done under pentobarbitone anaesthesia. Two were excluded because they developed ventricular fibrillation soon after coronary occlusion, and one did not survive reflow ventricular fibrillation. Of the remaining 18 dogs, six developed reflow ventricular fibrillation and were compared to the control group of 12 which did not develop fibrillation. MEASUREMENTS and RESULTS - A mean of 70.8(SEM 18.7) joules was required to revive the six dogs with reflow ventricular fibrillation. Difference in mean infarct size in the two groups did not reach significance [49.1(4.4) in fibrillation group v 38(6.2) in the controls]. The multiple linear regression model in the control group accounted for 91% of the variation in infarct size (IS): IS = -3.4 + 0.49 (AR) -21.8 (MBF) + 0.025 (RPP). The equation was not modified by including the reflow fibrillation dogs: IS = -3.1 + 0.52 (AR) - 19 (MBF) + 0.02 (RPP). Ischaemic determinants of infarct size in the reflow fibrillation dogs were computed in the control group equation to compare the infarct size predicted by the model to the measured infarct size in each individual dog in the reflow fibrillation group. There was no significant difference between the means: 12.9(2.9)% (predicted) v 14.9(2.5)% (measured). CONCLUSIONS - In this model of myocardial infarction, reflow ventricular fibrillation and low energy internal electric shocks do not damage the myocardium at risk significantly.

Animals↗
PubMed1990

Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium.

To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.

Animals↗
PubMed1989

Influence of leukopenia on collateral flow, reperfusion flow, reflow ventricular fibrillation, and infarct size in dogs.

Leukocytes contribute to myocardial damage during ischemia and reperfusion. However, the mechanism involved has not been clearly elucidated. The purpose of the present study was to determine whether leukocyte-induced myocardial damage is flow mediated. In open-chest dogs submitted to 2 hours of ischemia, area at risk, infarct size, and regional myocardial blood flow before, during, and after ischemia were measured. Leukopenia was induced by a two-step method (chemotherapy and antineutrophil serum) in a group of 14 dogs as compared to a control group of 18 dogs. The relation of infarct size to the major determinants of infarct size was analyzed by uni- and multilinear regressions. Seven control dogs had ventricular fibrillation at reperfusion compared to one dog with leukopenia. In the group with leukopenia the mean infarct size was smaller (31.1 +/- 5.8% of area at risk) than in the control group (47.7 +/- 2.9, p = 0.02). In addition, the two multiple linear regression equations were significantly different (p = 0.01). Myocardial blood flow to the central ischemic zone did not change significantly between 20 and 120 minutes of ischemia in the control dogs (n = 12; subendocardial = 0.08 +/- 0.03 vs 0.07 +/- 0.03 ml/min/gm; subepicardial = 0.20 +/- 0.07 vs 0.20 +/- 0.05 ml/min/gm) and in the dogs with leukopenia (n = 12; 0.07 +/- 0.02 vs 0.07 +/- 0.02 ml/min/gm and 0.15 +/- 0.004 vs 0.18 +/- 0.04 ml/min/gm). A similar reduction in myocardial blood flow was observed after 6 hours of reperfusion in the control dogs (0.34 +/- 0.07 ml/min/gm vs 1.02 +/- 0.11 at baseline, p less than 0.01) and in the dogs with leukopenia (0.25 +/- 0.04 vs 0.81 +/- 0.08 ml/min/gm, p less than 0.01). It was concluded that the leukocyte-dependent myocardial injury did not appear to be mediated through a flow mechanism during either ischemia or reperfusion.

Animals↗
PubMed1989

Effects of manganese chloride, verapamil, and hypoxia on the rate-dependent increase in internal longitudinal resistance of rabbit myocardium.

The effects of high rates of stimulation on the internal longitudinal restivity (Ri) and conduction velocity (theta) were studied on rabbit papillary muscle preparations using a silicon-oil chamber. Increasing the rate from 75 to 150/min caused Ri to rise and theta to decrease. The maximum rate of depolarization and action potential duration were also decreased. At a rate of 300/min the effects were more pronounced. Blockade of the slow inward current (Isi) and of the Na-Ca exchange by MnCl2 (5 mmol/L) did not prevent rate-induced changes in these variable. Verapamil (0.02 mmol/L) was also ineffective. Hypoxia (PO2 = 5.3 kPa) at 75/min induced changes in Ri and theta which were similar to those recorded at 150/min under aerobic conditions. The effects of high rates of stimulation were potentiated under hypoxia. From the present results it is suggested that Isi and the Na-Ca exchange are not the main determinants of the rate-induced increase in Ri, which could be determined by other intracellular Ca-release mechanisms or by a decrease in myoplasmic pH.

Animals↗
PubMed1988

Lignocaine in experimental myocardial infarction: failure to prevent neutrophil accumulation and ventricular fibrillation and to reduce infarct size.

Growing evidence supports the concept that neutrophils accumulating in reperfused ischaemic myocardium play a detrimental role in evolving infarction. Lignocaine, an antiarrhythmic drug commonly used clinically, interferes with neutrophil function in vitro and potentially in vivo. To test the hypothesis that lignocaine may influence infarct size by reducing neutrophil accumulation in reperfused ischaemic myocardium, 31 dogs underwent a 2 h occlusion of the left anterior descending coronary artery, followed by 6 h of reperfusion. One group of dogs received saline (controls) the other a perfusion of lignocaine 0.06 mg.kg-1.min-1 starting 30 min before coronary occlusion and lasting for the duration of the experiment. Blood lignocaine concentrations at the onset of reperfusion were 3.3(0.6) micrograms.ml-1. 111Indium labelled autologous neutrophils were injected at the time of occlusion and their accumulation in the myocardium measured by digital scintigraphy of heart slices. The area at risk and infarct size were evaluated by planimetry of the heart slices (7 mm) after perfusion of Evans blue dye and triphenyltetrazolium staining. Ventricular fibrillation occurred in six controls and in five dogs receiving lignocaine. The phenomenon occurred early during the occlusion period in the lignocaine group (five dogs) and at reperfusion in controls (five dogs; p less than 0.05). In the remaining 20 dogs, 10 in each group, a linear correlation was found between myocardial 111In labelled neutrophil and circulating neutrophil counts at the onset of reperfusion (r = 0.076, p less than 0.05) and with infarct size (r = 0.96 and 0.74, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗