Discordant lung xenograft rejection in the rat.
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Animals↗
Biomedical subjects
J Y Devaux
Publications and source records attributed to J Y Devaux.
[Technique and results of lung transplantation in rats].
Lung transplantation has recently emerged as an efficient therapy for a variety of endstage pulmonary diseases. Nevertheless, many problems remain unsolved. A simple and reproducible experimental model allows examination of some of the problems encountered. We report here our experience of lung transplantation in the rat. One hundred and thirty six lung transplantations have been performed. After the initial phase necessary to master the technique, an overall survival rate of 86% was achieved. Graft function, as assessed by chest X-rays and lung isotope scans, was satisfactory up to 4 months after transplantation. Lung transplantation in the rat is a reliable and reproductible experimental model allowing the development of research projects in this field.
Animals↗
Automated analysis of the McKenzie test through color slide digitization and processing.
The McKenzie test is performed to compare the antiinflammatory activity of topical corticosteroids. Each drug induces a local whiteness of the skin called blanching. The blanchings are classically evaluated on the basis of visual score. This paper proposes a new blanching index and a methodology for designing such an index by digitizing and processing color slides. Several indices derived from classical color models are proposed and compared to the visual scores. This work demonstrates the significant improvement of quantitation derived from digitized images with respect to the observer assessment. The difference of chromatic green between the blanching patch and the surrounded healthy skin is proposed for analysis of the McKenzie test.
Administration, Topical↗
Role of tricuspid regurgitation and left ventricular damage in the treatment of right ventricular infarction-induced low cardiac output syndrome.
To evaluate, in right ventricular (RV) myocardial infarction, the role of tricuspid regurgitation (TR) and left ventricular (LV) damage and the response to treatment of low cardiac output, 20 patients were prospectively studied. Volume infusion increased cardiac output only slightly (11%, p less than 0.001), despite a dramatic increase in ventricular filling pressures. Dobutamine (4 micrograms.kg-1.min-1) markedly increased cardiac output (24%, p less than 0.001) with a decrease in ventricular filling pressures. In the 5 patients with TR, dobutamine only modestly increased cardiac output (9 vs 26%, p less than 0.001), while stroke index and LV end-diastolic dimensions decreased in comparison (-5 vs 33% and -6 vs 9%, respectively, p less than 0.001). In the absence of TR (n = 15), there was no significant difference in response to volume expansion between patients with normal (n = 7) and depressed LV ejection fraction (n = 8). In contrast, dobutamine, in patients with depressed LV function, induced a greater increase in cardiac output (38 vs 17%, p less than 0.01) and RV ejection fraction (36 vs 12%, p less than 0.05). All patients with RV infarction-induced low cardiac output responded only modestly to volume loading. Dobutamine is particularly efficacious in patients without TR who have depressed LV function by improving RV function and, consequently, LV preload. In the 5 patients with TR, increasing RV contractility failed to improve the forward stroke volume by increasing the regurgitant fraction.
Adult↗
The effect of captopril on thallium 201 myocardial perfusion in systemic sclerosis.
In systemic sclerosis, abnormalities of myocardial perfusion are common and may be caused by a disturbance of the coronary microcirculation. We evaluated the long-term effect of captopril (75 to 150 mg per day) on thallium 201 myocardial perfusion in 12 normotensive patients with systemic sclerosis. Captopril significantly decreased the mean (+/- SD) number of segments with thallium 201 myocardial perfusion defects (6.5 +/- 1.9 at baseline and 4.4 +/- 2.7 after 1 year of treatment with captopril; p less than 0.02) and increased the mean global thallium score (9.6 +/- 1.7 at baseline and 11.4 +/- 2.1 after captopril; p less than 0.05). In a control group of eight normotensive patients with systemic sclerosis who did not receive captopril, no significant modification in thallium results occurred. Side effects with captopril included hypotension (six patients), taste disturbances (one patient), and skin rash (one patient). These side effects subsided when the dosage was reduced. These findings demonstrate that captopril improves thallium 201 myocardial perfusion in patients with systemic sclerosis and may therefore have a beneficial effect on scleroderma myocardial disease.
Adult↗
Pharmacodynamic effect of nicardipine on left ventricular function in systemic sclerosis.
Left ventricular dysfunction in systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance in coronary microcirculation. We evaluated the pharmacodynamic effect of the calcium channel blocker nicardipine on left ventricular function assessed by radionuclide ventriculography in 20 patients with systemic sclerosis. Resting gated, blood-pool images were obtained at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SEM) left ventricular ejection fraction significantly increased from 65.4 +/- 2.3% at baseline to 71.3 +/- 2.3% after nicardipine (p less than 0.005). The mean global defect score significantly decreased from 2.90 +/- 0.73 without nicardipine to 1.50 +/- 0.52 with nicardipine (p less than 0.01). The mean number of left ventricular sectors with severe hypokinesis significantly decreased from 0.80 +/- 0.24 at baseline to 0.20 +/- 0.09 after nicardipine (p less than 0.05). No significant side effects were observed with nicardipine. These results demonstrate short-term improvement in left ventricular function with nicardipine in patients with systemic sclerosis.
Adult↗
[Xenogeneic hyperacute rejection of the lung in rats].
Xenotransplantation, with organs harvested from appropriate donor animals could be a potential solution to the shortage of donor organs in general and of lung grafts in particular. Unilateral orthotopic lung transplantation in the rat has been used to study the lung xenograft rejection in a discordant donor-recipient combination, i.e. guinea-pig to rat. With this microsurgical technique, a high post-operative survival rate has been reached. The good function of the grafts was assessed by serial chest x-ray, lung perfusion scintigraphy until several months after the transplantation. The survival of the xenografts has been then compared to that of allografts and isografts. Lung xenograft rejection in this combination has been very fast: 53 minutes. Macroscopic and histologic data displayed lung infarct with hemorrhagic edema.
Animals↗
[Angina without involvement of large coronary trunks and precapillary pulmonary hypertension in a patient with periarteritis nodosa].
A patient affected with periarteritis nodosa and angina, presented a normal coronary angiography of the coronary trunks and an alteration of the left ventricular systolic function, improved by nicardipine, as well as a pre-capillary pulmonary hypertension with isolated, right cardiac repercussions, without pulmonary fibrosis nor thromboembolic disease. In addition, he presented three transient cerebral ischaemic accidents, with different localizations, which could not be related to a right aneurysm of the sylvian artery. Isolated precapillary pulmonary hypertension, without pulmonary fibrosis, which is not described in the course of periarteritis nodosa, seems related to an arteriolar involvement which is the known substratum of other visceral involvement in periarteritis nodosa. Improvement of the left ventricular function with nicardipine, administered acutely, suggest a partially reversible disorder of the coronary microcirculation.
Angina Pectoris↗
Right ventricular performance in patients with acute respiratory failure.
To examine the right ventricular response to acute respiratory failure, serial studies of biventricular performance were analysed in 34 such patients, specifically detailing the role of associated underlying disease. During the initial study, the 34 patients with acute respiratory failure had a higher right ventricular end-diastolic volume than the control group (+21%), associated with a decrease in right ventricular ejection fraction, abnormalities which tended to return to normal values in the 15 survivors. In the 9 patients who died of refractory hypoxemia with severe pulmonary hypertension, the right ventricular dilation allowed to maintain stroke volume. In contrast, in 8 patients who died of septic shock, biventricular function was progressively altered (right and left ventricular ejection fraction = -37% and -35%). In 4 patients who died of cardiogenic shock (viral myocarditis), the cardiac function was the lowest (right and left ventricular ejection fraction = -59% and -60%). Only patients with acute respiratory failure associated with septic shock or viral myocarditis are unable to maintain their stroke volume.
Acute Disease↗
[Myocardial microvascularization in scleroderma].
Myocardial involvement in systemic sclerosis may be caused, at least in part, by myocardial ischemia due to functional or structural abnormalities of small coronary arteries or arterioles. Coronary reserve, assessed by dipyridamole-induced coronary vasodilatation, was strikingly impaired in patients with systemic sclerosis. Thallium scans have shown numerous myocardial perfusion defects in scleroderma patients. Two studies, using oral nifedipine and intravenous dipyridamole, demonstrated that these thallium-201 myocardial perfusion defects in patients with systemic sclerosis were partially reversible. Finally, the preliminary results of long-term studies suggest that some coronary vasodilators may be beneficial in the long-term treatment of myocardial perfusion abnormalities in systemic sclerosis.
Coronary Circulation↗
Nicardipine improves myocardial perfusion in systemic sclerosis.
Primary scleroderma myocardial disease may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. We evaluated the effect of the calcium channel blocker nicardipine on myocardial perfusion assessed by thallium-201 scanning in 16 patients with systemic sclerosis. Thallium-201 single photon emission computerized tomography was performed at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SD) number of left ventricular segments with perfusion defects significantly decreased from 6.0 +/- 2.0 at baseline to 4.1 +/- 2.3 after nicardipine (p less than 0.01). The mean global perfusion score significantly increased from 10.2 +/- 1.9 at baseline to 11.9 +/- 2.6 after nicardipine (p less than 0.02). Our study demonstrates short-term improvement in thallium-201 myocardial perfusion with nicardipine in patients with systemic sclerosis.
Adult↗
Bedside evaluation of right ventricular performance using a rapid computerized thermodilution method.
In 34 patients, we assessed the reproducibility and accuracy of a new, computerized, thermodilution method that determines right ventricular ejection fraction (RVEF). We compared the results from this new algorithm with simultaneous results from the conventional plateau thermodilution method and from both first-pass and gated nuclear techniques. Using this new method improved the reproducibility of thermal determinations of RVEF. Although the thermal values were lower, the correlations between thermal and nuclear measurements were close [r = .92 (first-pass technique), r = .81 (gated technique)]. This new method seems particularly appropriate for serial monitoring of RV performance.
Adult↗
Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis.
Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.
Adult↗
Reduced coronary flow and resistance reserve in primary scleroderma myocardial disease.
The maximum coronary vasodilator capacity after intravenous dipyridamole (0.14 mg X kg-1 X min-1 X 4 minutes) was studied in seven patients with primary scleroderma myocardial disease and compared to that of seven control subjects. Hemodynamic data and left ventricular angiographic data were not different in the two groups. The coronary flow reserve was evaluated by the dipyridamole/basal coronary sinus blood flow ratio (D/B CSBF) and the coronary resistance reserve by the dipyridamole/basal coronary resistance ratio (D/B CR). Coronary reserve was greatly impaired in the group with primary scleroderma myocardial disease: D/B CSBF was lower than in the control group (2.54 +/- 1.37 vs 4.01 +/- 0.56, respectively; p less than 0.05) and D/B CR was higher than in the control group (0.47 +/- 0.25 vs 0.23 +/- 0.04, respectively; p less than 0.05). Such a decreased coronary flow and resistance reserve in patients with primary scleroderma myocardial disease was not explained by an alteration of left ventricular function. It may be an important contributing factor in the pathogenesis of primary scleroderma myocardial disease.
Adult↗
Pharmacodynamic effect of dipyridamole on thallium-201 myocardial perfusion in progressive systemic sclerosis with diffuse scleroderma.
We evaluated the effect of dipyridamole on thallium-201 myocardial perfusion in 23 patients with progressive systemic sclerosis (PSS) with diffuse scleroderma. Thallium-201 single photon emission computed tomography (SPECT) was performed at rest and after coronary artery vasodilatation with intravenous dipyridamole (0.14 mg/kg/min for four minutes). The left myocardium was divided into nine segments; each segment was graded as 2.0, 1.5, 1.0, 0.5, 0 (zero represents no activity). Dipyridamole significantly improved resting thallium-201 myocardial perfusion: the mean (SD) number of segments with thallium defects decreased from 6.0 (2.1) at rest to 4.1 (2.5) after dipyridamole (p less than 0.0001); the mean (SD) score in segments with resting defects increased from 0.92 (0.24) at rest to 1.13 (0.38) after dipyridamole (p less than 0.0001); the mean (SD) global score per patient increased from 10.2 (1.8) at rest to 11.4 (2.1) after dipyridamole (p less than 0.02); the global score increased by at least 2.0 in 12 patients and worsened by at least 2.0 in three patients only (p = 0.05). The results of this acute study suggest that some drugs with potent vasodilator activity on small coronary arteries may be beneficial in the treatment of PSS patients with thallium-201 myocardial perfusion abnormalities.
Adult↗
Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS.
Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes were then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H2O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H2O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.
Adult↗
[Cardiac manifestations of rapidly progressive Duchenne's disease. A tentative evaluation of the operative risks during the surgical correction of spinal deformities].
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Adolescent↗
Decreased coronary reserve in primary scleroderma myocardial disease.
We assessed coronary reserve, by measuring the increase in coronary sinus blood flow (CSBF) after intravenous administration of dipyridamole (0.14 mg/kg/minute for 4 minutes), in 7 patients with primary scleroderma myocardial disease (PSMD) and in 7 control subjects. Coronary reserve was greatly impaired in PSMD: before administration of dipyridamole, CSBF was similar in patients with PSMD (89 +/- 32 ml/minute/100 gm, mean +/- SD) and in controls (100 +/- 15 ml/minute/100 gm); after dipyridamole infusion, CSBF was significantly lower in patients with PSMD (191 +/- 45 ml/minute/100 gm) than in controls (399 +/- 58 ml/minute/100 gm) (P less than 0.01). Six of the 7 patients with PSMD had angiographically normal epicardial coronary arteries and normal left ventricular function. Decreased coronary reserve may be an important contributor to the pathogenesis of primary scleroderma myocardial disease.
Adult↗