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Biomedical subjects

G Vassalli

Publications and source records attributed to G Vassalli.

48 records · Page 3Linked to original sources

Clinical significance of coronary flow reserve: effect of papaverine and exercise.

BACKGROUND: The clinical significance of coronary flow reserve (CFR) was evaluated after pharmacological (papaverine) and physiological (exercise) vasodilation in patients with coronary artery disease (CAD). METHODS: CFR was determined using parametric imaging in 10 patients with normal coronary arteries (group 1) and in 10 with CAD (group 2). Contrast density and mean appearance time were measured (region of interest = 249 pixels) in the perfusion beds of the left circumflex and the left anterior descending coronary arteries at rest, 45 s after 10 mg intracoronary papaverine, and during supine bicycle exercise. CFR was calculated from coronary perfusion after papaverine divided by perfusion at rest and coronary perfusion during exercise divided by perfusion at rest. Perfusion zones in patients with CAD were subdivided into regions supplied by a non-stenosed (group 2a) and a stenosed (group 2b) coronary artery. RESULTS: In control patients, heart rate increased from 75 beats/min at rest to 125 beats/min during exercise, and in patients with CAD from 63 to 107 beats/min, respectively. Mean aortic pressure showed a significant increase during exercise in both groups. Mean pulmonary artery pressure increased significantly during exercise from 19 to 28 mmHg in control patients and from 22 to 42 mmHg in the CAD group (P < 0.001). Coronary driving pressure (mean aortic minus diastolic pulmonary artery pressure) tended to increase during exercise in the control group (from 90 to 101 mmHg, NS) and remained nearly unchanged in patients with CAD (from 92 to 94 mmHg, NS). In the control group, CFR was significantly higher during exercise than after papaverine (4.0 versus 3.5, respectively; P < 0.01). However, coronary resistance (coronary driving pressure divided by coronary flow index) was similar after papaverine and during exercise. In patients with CAD, papaverine-dependent CFR was significantly reduced in the perfusion zone of the stenosed (2.1) but not of the non-stenosed coronary artery (3.0). In contrast, CFR during exercise was significantly decreased in both perfusion zones (2.5 in non-stenosed arteries and 1.5 in stenosed vessels). CONCLUSIONS: In control patients, CFR is slightly but significantly larger during exercise than after papaverine because of the exercise-induced increase in coronary driving pressure. In contrast, CFR is smaller during exercise than after papaverine in patients with CAD, most probably as a result of secondary mechanisms such as exercise-induced narrowing of stenosed vessels or an increase in extravascular resistance. Thus, CFR based on papaverine appears to be of limited value for assessing the functional significance of a stenotic lesion.

Adolescent↗

[Heart function in chronic pressure overload caused by aortic stenosis: the role of collagen tissue].

The purpose of this study was to evaluate left ventricular (LV) structure-function interplay in aortic stenosis. LV structure was assessed from endomyocardial biopsies obtained in 27 patients with aortic stenosis. Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching) and endocardial fibrosis were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from 6 pre-transplantation donor hearts whereas other 11 patients with normal cardiac function served as hemodynamic controls. LV biplane cineangiography and high-fidelity LV pressure measurement were carried out in all patients. Systolic function was assessed by LV biplane ejection fraction, diastolic function by time constant of relaxation, peak filling rates and passive elastic properties. Total collagen volume fraction (7.3 versus 1.6%, p < 0.01) as well as the degree of cross-hatching (1.7 versus 0.8 grade, p < 0.01) were significantly increased in patients with aortic stenosis with respect to controls. Endocardial fibrosis was present in 11/27 patients with aortic stenosis and in no patients of control group. In aortic stenosis in presence of increased total collagen volume fraction there were no changes in systolic and diastolic function, whereas in presence of changes in collagen architecture ejection fraction was depressed and passive elastic properties increased. In conclusion, in aortic stenosis, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered. A prolongation of relaxation was present in aortic stenosis and appears to be mediated by muscle hypertrophy per se.

Aged↗

Influence of collagen network on left ventricular systolic and diastolic function in aortic valve disease.

OBJECTIVES: The purpose of this study was to evaluate left ventricular structure-function interplay in aortic valve disease. BACKGROUND: An increase in myocardial fibrosis has been demonstrated in aortic valve disease, but changes in the collagen network and their effect on ventricular function have not been defined. METHODS: Left ventricular structure was assessed from left ventricular endomyocardial biopsy specimens obtained in 32 patients with aortic valve disease (aortic stenosis in 25, aortic regurgitation in 7). Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching), endocardial fibrosis, muscle fiber diameter and volume fraction of myofibrils were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from six donor hearts before transplantation. Eleven other patients with normal left ventricular function served as hemodynamic status control subjects. Left ventricular biplane cineangiography and high fidelity pressure measurements were carried out in all patients. Systolic function was assessed from ejection fraction. Diastolic function was evaluated by the time constant of relaxation, early and late peak filling rates and the constant of passive myocardial stiffness. Patients were assigned to three groups according to increasing severity of nonmyocyte tissue alterations. Group 1 comprised 10 patients with elevated total collagen volume fraction. Group 2 comprised 6 patients with normal total collagen volume fraction and the presence of increased cross-hatching or endocardial fibrosis, or both. Group 3 comprised 16 patients with elevated total collagen volume fraction and the presence of cross-hatching or endocardial fibrosis, or both. RESULTS: Muscle fiber diameter was increased in the three groups with aortic valve disease, whereas the volume fraction of myofibrils was comparable in all four study groups. Ejection fraction was depressed in groups 2 and 3 compared with the control group. The time constant of relaxation was prolonged in the three groups with aortic valve disease. No differences in early and late peak filling rate were observed in the four study groups, but the constant of myocardial stiffness increased in groups 2 and 3. CONCLUSIONS: In aortic valve disease, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered.

Adult↗

[Coronary artery size in chronic mitral valve insufficiency before and following mitral valve surgery].

The increase of coronary artery size in myocardial hypertrophy represents an adaptive mechanism to keep coronary blood flow normal. The relationship between coronary cross-sectional area and left ventricular muscle mass was determined angiographically in 10 patients with severe mitral regurgitation before and 28 +/- 15 months after successful mitral valve surgery. 10 subjects with atypical chest pain without coronary artery disease served as controls (C). Left ventricular muscle mass was increased preoperatively in mitral regurgitation (257 g vs C = 129 g; p < 0.001) and decreased postoperatively (205 g; p < 0.01 vs preop. and vs C). The cross-sectional area of the left coronary (= left anterior descending+left circumflex) artery was augmented preoperatively (26.5 vs C = 14.0 mm2; p < 0.001) and decreased postoperatively (22.9 mm2; p < 0.05 vs preop. and vs C). The cross-sectional area of the left coronary artery per 100 g LV muscle mass was not different in the three groups. The cross-sectional area of the right coronary artery was also increased before surgery (12.7 vs C = 8.8 mm2; p < 0.05) and decreased postoperatively (11.3 mm2; p < 0.05 vs preop. ns vs C). Our data show that in mitral regurgitation the size of the left coronary artery increases proportionally to the increase in left ventricular muscle mass. Also, the right coronary artery shows slight enlargement which is probably due to the pressure overload of the right ventricle. After surgery there is regression but not normalization of the size of the coronary arteries.

Chronic Disease↗

Is atrial pacing needed for determination of coronary flow reserve by parametric imaging?

Heart rate changes during determination of coronary flow by parametric imaging may influence the flow measurement. Thus, the question is whether atrial pacing is mandatory for determination of coronary flow reserve (CFR) by this technique. CFR was calculated by digital subtraction angiography (parametric imaging) in 10 patients (8 with coronary artery disease and 2 control subjects) during sinus rhythm and during atrial pacing. Flow measurements were determined in the perfusion region of the left anterior descending and circumflex coronary artery, both at rest and after maximal coronary vasodilation with 10 mg intracoronary papaverine. CFR was defined as coronary flow during hyperemia divided by coronary flow at rest. Spontaneous heart rate was 71 +/- 15 min-1 at baseline, 73 +/- 15 min-1 after papaverine injection and 85 +/- 10 min-1 during atrial pacing. Heart rate variations during coronary arteriography were 4 +/- 3 min-1 at baseline and 5 +/- 4 min-1 after papaverine administration. CFR was 2.61 +/- 1.01 during sinus rhythm and 2.67 +/- 1.05 during atrial pacing. Mean absolute difference in CFR between sinus rhythm and atrial pacing was 0.31 +/- 0.31 (12 +/- 10% of CFR during pacing). Spontaneous heart rate variations during coronary arteriography are not associated with significant changes in CFR. Thus, atrial pacing is not mandatory for the determination of CFR by parametric imaging.

Angiography, Digital Subtraction↗

Coronary artery size in mitral regurgitation and its regression after mitral valve surgery.

The relationship between coronary artery size and left ventricular (LV) muscle mass was studied in 10 control subjects and in 10 patients with chronic mitral regurgitation before and 28 +/- 15 months after mitral valve surgery. Left and right coronary artery size was determined by quantitative coronary arteriography. Left coronary artery size was significantly increased before surgery (26 mm2) and decreased after operation (23 mm2), but was still larger than in control subjects (14 mm2). The right coronary artery was also enlarged preoperatively (13 mm2; controls = 9 mm2), but was normalized after surgery (11 mm2). A linear correlation was found between LV muscle mass and left (r = 0.88, p < 0.001) and right coronary artery size (r = 0.84, p < 0.001) as well as between right coronary artery size and mean pulmonary artery pressure (r = 0.56, p < 0.01). Thus in chronic mitral regurgitation the enlargement of the left and right coronary artery is proportional to the degree of LV hypertrophy. The increase in right coronary artery size is probably the result of right ventricular pressure overload. Postoperatively there is only partial regression of left coronary artery size but normalization of right coronary artery size.

Adult↗

Bronchoconstrictive responses to inhaled ultrasonically nebulized distilled water and airway inflammation in asthma.

Twenty-two asthmatic patients with a range of airway hyperresponsiveness to methacholine underwent a bronchial challenge with ultrasonically nebulized distilled water (UNDW). The presence of positive responses to this stimulus was related to the extent of airway inflammation, as assessed by histochemical and immunohistochemical evaluation of bronchial biopsy specimens. Twelve patients had airflow obstruction during distilled water inhalation and they showed more severe disease than subjects with no response, as demonstrated by the higher degree of nonspecific bronchial hyperresponsiveness (p < 0.01), higher variability of peak expiratory flow rates (p < 0.01), symptom scores (p < 0.01), and daily use of bronchodilators (p < 0.01). Those patients also had increased numbers of mast cells and eosinophils (p < 0.01) and increased percentage of bronchial epithelial cells expressing endothelin 1 immunoreactivity (p < 0.01). Thus, positive responses to inhaled UNDW reflect the bronchial hyperresponsiveness consistent with moderate to severe asthma and may be due to the release of mediators with bronchoconstrictive properties from inflammatory cells or activated resident cells or both.

Adult↗

Effect of progression of left ventricular hypertrophy on coronary artery dimensions in aortic valve disease.

OBJECTIVES: The effect of progression of left ventricular hypertrophy on coronary artery dimensions was studied in patients with aortic valve disease. METHODS: Cross-sectional area of the left and right coronary arteries was determined by quantitative coronary arteriography in 12 control subjects and in 10 patients with aortic valve disease at baseline and after a follow-up period of 66 months. RESULTS: The cross-sectional area of the left coronary artery was larger in patients with aortic valve disease than in control subjects (left anterior descending artery 13 vs. 8 mm2, p < 0.001; left circumflex artery 13 vs. 6 mm2, p < 0.001). At the follow-up examination, cross-sectional area of the left coronary artery increased (left anterior descending artery 17 mm2, p < 0.01 vs. baseline; left circumflex artery 15 mm2, p < 0.01 vs. baseline). The cross-sectional area of the right coronary artery was not different in patients with aortic valve disease from that in control subjects. Left ventricular muscle mass was larger in patients with aortic valve disease both at baseline (269 g, p < 0.001) and after follow-up examination (339 g, p < 0.001) than in control subjects (136 g). The appropriateness of coronary artery size with respect to muscle mass was evaluated by normalizing cross-sectional area of the left coronary artery (left anterior descending plus left circumflex artery) per 100 g of left ventricular muscle mass (mm2/100 g). This index was 10.9 mm2/100 g in control subjects, and decreased in subjects with aortic valve disease from 10.3 mm2/100 g at baseline to 8.6 mm2/100 g at the follow-up measurement (p < 0.05 vs. control values). CONCLUSIONS: In patients with aortic valve disease, the progression of left ventricular hypertrophy is associated with an increase in left anterior descending and left circumflex coronary artery dimensions, whereas the size of the right coronary artery remains unchanged. Despite the enlargement of the left coronary artery, the cross-sectional area of the left coronary artery per 100 g of left ventricular muscle mass decreased. Hence, the increase in coronary artery size appears to be inadequate when the severity of left ventricular hypertrophy increases.

Adult↗

[Cat-scratch disease].

Cat-scratch disease is usually a self-limited illness characterized by regional lymphadenopathy and a skin inoculation lesion. These findings generally resolve spontaneously over a period of several weeks or months. The discovery of the causative organism, an intracellular gram-negative rod and the recognition of severe systemic courses in immuno-compromised patients have renewed the interest in this disease. We report a prolonged clinical course with lymph node suppuration in an immunocompetent patient. The diagnosis was confirmed by the detection of the organism in Warthin-Starry silver stained lymph node biopsy.

Adult↗

Ig allotype-linked regulation of class and subclass composition of natural antibodies to group A streptococcal carbohydrate.

To determine the importance of genes located in or near the Ig constant regions in regulating the human antibody response, we correlated Ig allotypic markers with total Ig concentrations and natural antibody concentrations to the streptococcal group A carbohydrate (A-CHO) in 193 healthy adult blood donors. The major correlations between Ig allotypes and total Ig and specific antibody concentrations were observed with the Gm(f;n;b) haplotype. When compared with Gm(f;n;b) negative individuals, Gm(f;n;b) positives had significantly higher concentrations of total IgG2 (p less than 0.001) and IgG2 anti A-CHO (p less than 0.05), lower concentrations of total IgG1 (p less than 0.001) and IgG1 anti A-CHO (p less than 0.001), and lower concentrations of total IgM (p less than 0.001) and IgM anti A-CHO (p less than 0.05). We conclude that individuals with the Gm(f;n;b) haplotype respond preferentially with IgG2 rather than IgG1 subclass antibodies. This increased capacity to respond with IgG2 antibodies may be reflected in the magnitude of the total antibody response when the IgG2 subclass comprises a major proportion of the response, as occurs in the adult response to many polysaccharide Ag.

Adult↗

The proliferative response of human peripheral blood lymphocytes to group A streptococcal vaccine.

The proliferative response of human peripheral blood mononuclear cells to group A streptococcal vaccine (strain J17A4) was assessed by measurement of [3H]thymidine incorporation. This was maximal after 7 days in cultures containing 1 X 10(5) lymphocytes. Cells from 33 out of 38 adult donors (87%) yielded stimulation indices between 2.0 and 81. Responding cells were predominantly of the OKT4+, Ia+, Tac+ phenotype expressed by activated helper T lymphocytes. In contrast, no response was observed in 10 out of 12 samples of cord blood lymphocytes. Addition of conventional rabbit or monoclonal murine anti-Ia (HLA-DR) antibodies to the culture medium abrogated the vaccine-induced proliferative response. Frequencies of responding cells estimated by limiting dilution analysis were between 1 in 2370 and 1 in 4580 lymphocytes. The results suggest that lymphocyte stimulations induced with streptococcal group A vaccine represented an in vitro anamnestic cellular immune response.

Antibody-Producing Cells↗