Biomedical subjects
Publications and source records attributed to A Cohen-Solal.
We report four cases in which oxygen intake abruptly decreased during a graded exercise test. In all these cases, there was an acute event (arrhythmia, mitral regurgitation) that had very likely resulted in a decrease in cardiac output. These studies provide new evidence of oxygen intake dependence on oxygen transport, even in nonsteady-state situations.
The ejection fraction (EF) is a load-dependent index of the systolic function of the left ventricle (LV), which depends on the 'functional' coupling of the LV with the arterial system, evaluated by the ratio between arterial effective elastance (Ea) to end-systolic left ventricular elastance. The spectrum of changes in LV and the arterial system during aging has not been studied by means of coupled analysis of elastances. Twenty-five normotensive healthy subjects aged from 22 to 68 years underwent hemodynamic and angiographic studies. The functional properties of the arterial system were evaluated in terms of Ea (end-systolic pressure/stroke volume), and the systolic function of the LV was approximated by the end-systolic pressure to end-systolic volume ratio (Elv). The result is that Ea increased linearly with age. Elv increased less than Ea. The positive relationship between Ea/Elv and age was close to statistical significance (r = 0.39, p = 0.07), suggesting that left ventricular-arterial coupling changes little with aging. Analysis of the relationship between EF and end-systolic stress showed that several points were situated at the lower part of the relationship in elderly subjects, suggesting a decrease in the intrinsic contractility of left ventricular muscle in some cases. Aging is characterized by a simultaneous increase in arterial system elastance and the systolic performance of the left ventricular pump, thereby preserving the transfer function of the arterial system as a whole. However, some aged subjects may depart from this rule, probably because of variability in the capacity to produce myocardial hypertrophy and/or altered inotropy of the muscle.
The betablockers are the most important drugs in the secondary prevention after myocardial infarction. Several studies have shown that, in patients without a contraindication to these drugs, betablockers reduce the mortality and recurrence of infarction by about 25%. The best results observed in the subgroup of patients with criteria of severity (previous myocardial infarction or cardiac failure, left ventricular dysfunction, arrhythmias, residual ischaemia, occluded artery or triple vessel disease) has been shown in the APSI and BHAT studies where the reduction in mortality was almost 50% in the subgroup of patients with cardiac failure. The duration of treatment and the role of betablockers with respect to ACE inhibitors are not as clearcut in 1996.
The improved diagnosis in chronic cardiac failure and the lack of donor hearts have lead to a reexamination of the indications of cardiac transplantation. In the absence of a contraindication, the indication is straightforward in class IV of the NYHA to improve quality of life. In less sympatomatic patients, the primary objectives are to improve the prognosis and prevent sudden death: the indication should be considered with respect to a range of criteria (the VO2 max and arrhythmogenic potential are important features) and the rate of progression of the disease (resistance to treatment, repeated episodes of decompensation). This indication may and should be reevaluated to optimise the distribution of the race donor hearts for the benefit of patient with the most to gain.
Independently of phenomena related to rejection, atherosclerosis of the grafted heart or high blood pressure, there exists a qualitative and quantitative degradation of response to exercise in heart transplant recipients. Maximal oxygen consumption is generally reduced to 40 to 60% of normal levels. There are several interactive mechanisms. Paradoxically, the transplanted heart is a clear demonstration of the fact that several other elements are involved in the organisms response to exercise. Indeed, ventilation, exercise load, peripheral circulation, muscle metabolism and neurohormonal response also play a role. Vasoactivity of the peripheral arteries limits distribution and extraction of oxygen during exercise. Noradrenaline, renin, atrial natriuretic factor, vasopressin and endothelin levels are normal at rest, but an overreaction occurs during exercise. The percentage of type I (oxidative) fibres is reduced in muscles. Cyclosporine has also been shown to have a toxic effect on mitochondria in muscles. The deinnervated transplanted heart is thus called upon to work in coordination with peripheral elements which have also undergone alterations. Consequently, response to exercise cannot be significantly increased above the level reached before transplantation. Usually patients are not greatly hindered in their daily activities and rarely complain of breathlessness. Nevertheless, an improvement would be appreciated. A coherent physical rehabilitation programme can increase maximal oxygen consumption by 25 to 30% in these patients, essentially via improvement in peripheral anomalies. It is more difficult to modify cardiac response.
Clinical, electrocardiographic, and thallium-201 single-photon emission computed tomography data were evaluated in 397 consecutive patients divided into 3 groups according to coronary hyperemic stimulation: 186 patients (group I; Ex) had maximal symptom-limited exercise ergometric stress testing, 93 patients (group II; Dip) had intravenous dipyridamole (0.7 to 0.8 mg/kg) stress testing, and 118 patients (group III; Dip+Ex) had dipyridamole (0.7 to 0.8 mg/kg) plus nonlimited (i.e., symptom-limited) exercise stress testing, achieving a maximal workload (mean +/- SD) of 102 +/- 37 W. Clinical tolerance was higher in Ex than in Dip groups (p < 0.01), and tended to be higher in Dip+Ex than in Dip groups (p = NS). Image quality--as judged by signal-to-noise ratios--was superior in Ex and Dip+Ex groups when compared with the Dip group (p < 0.01). Chest pain and electrocardiographic positivity were more frequent in the Dip+Ex group than in the Dip group (p < 0.05), despite more extensive coronary artery disease (CAD) in the Dip group; and reversible scintigraphic defects were more frequent in Dip+Ex versus Dip (p < 0.01) and in Ex versus Dip groups (p < 0.05) in patients with established CAD, as well as for the whole group. We conclude that, in patients unable to achieve 85% of their maximal predicted heart rate, the combination of high-dose dipyridamole plus nonlimited exercise stress testing is superior to dipyridamole stress testing alone, and comparable to maximal exercise testing.
A selective polyclonal antibody directed toward the C-terminal decapeptide common to the alpha subunits of Gq and G11 G proteins (G alpha q/G alpha 11) was prepared and used to investigate the subcellular distribution fo these proteins in WRK1 cells, a rat mammary tumor cell line. In immunoblots, the antibody recognized purified G alpha q and G alpha 11 proteins and labeled only two bands corresponding to these alpha subunits. Functional studies indicated that this antibody inhibited vasopressin- and guanosine 5'-[alpha-thio]triphosphate-sensitive phospholipase C activities. Immunofluorescence experiments done with this antibody revealed a filamentous labeling corresponding to intracytoplasmic and perimembranous actin-like filament structures. Colocalization of G alpha q/G alpha 11 and F-actin filaments (F-actin) was demonstrated by double-labeling experiments with anti-G alpha q/G alpha 11 and anti-actin antibodies. Immunoblot analysis of membrane, cytoskeletal, and F-actin-rich fractions confirmed the close association of G alpha q/G alpha 11 with actin. Large amounts of G alpha q/G alpha 11 were recovered in the desmin- and tubulin-free F-actin-rich fraction obtained by a double depolymerization-repolymerization cycle. Disorganization of F-actin filaments with cytochalasin D preserved G alpha q/G alpha 11 and F-actin colocalization but partially inhibited vasopressin- and fluoroaluminate-sensitive phospholipase C activity, suggesting that actin-associated G alpha q/G alpha 11 proteins play a role in signal transduction.
BACKGROUND: Patients with chronic heart failure (CHF) often complain of prolonged dyspnea after exercise. The determinants of oxygen consumption after exercise in these patients are unknown. We hypothesized that the kinetics of oxygen consumption recovery after graded exercise was prolonged in parallel with the recovery of muscle energy stores, was not affected by the exercise level, and could be used to assess the circulatory response to exercise. METHODS AND RESULTS: Seventy-two patients with CHF in Weber's class A (n = 28), B (n = 21), and C/D (n = 23) and 13 healthy subjects performed maximal upright bicycle exercise with breath-by-breath respiratory gas analysis. Kinetics of recovery of ventilation (VE), oxygen consumption (VO2), and CO2 production (VCO2) after exercise were characterized by T1/2, the time to reach 50% of the peak value. T1/2 VO2 (seconds) increased with the severity of CHF (97 +/- 17 for CHF A [P < .05 versus CHF B, P < .05 versus CHF C/D], 119 +/- 22 for CHF B [P < .05 versus control subjects, P < .05 versus CHF A, and P < .05 versus CHF C/D], 155 +/- 55 for CHF C/D [P < .05 versus control subjects, P < .05 versus CHF A, and P < .05 versus CHF B] compared with 77 +/- 17 for control subjects). T1/2 VCO2 and T1/2 VE also increased similarly with the worsening of CHF. T1/2 VO2 was correlated negatively with peak VO2 (r = .65) and was reproducible (r = .96). To study the relation between T1/2 VO2 and the duration of exercise, 10 healthy subjects and 22 patients underwent a second graded test at 75% and/or 50% of peak workload. T1/2 VO2 was minimally shortened, at only 50% of peak workload (P = .02). Finally, 19 patients underwent 31P nuclear magnetic resonance spectroscopy of the anterior compartment of the leg during exercise; the half-time of recovery of the ratio of inorganic phosphate to creatine phosphate (T1/2 Pi/PCr), reflecting the level of involvement of oxidative metabolism in the restoration of energetic metabolites after exercise, was linearly correlated with the half-time of VO2 recovery (r = .70, P < .01). CONCLUSIONS: Postexercise T1/2 VO2 increases when CHF worsens, perhaps in part a result of slower kinetics of recovery of muscle energy stores. The time course of oxygen consumption recovery may represent a simple new criterion for measuring the impairment of the circulatory response to exercise in CHF, even submaximal exercise.
The quantitative relation between ST-segment changes and the severity and extent of myocardial ischemia during coronary occlusion remains unclear. This study assesses whether ST-segment changes during percutaneous transluminal coronary angioplasty (PTCA) correlate with the amount of myocardium at risk, measured with technetium-99m hexakis 2-methoxyisobutyl isonitrile (MIBI; also called sestamibi) single-photon emission computed tomography (SPECT). Quantitative continuous dynamic vectorcardiography was performed during PTCA of the left anterior descending coronary artery in 11 patients (mean age 64.3 years) without previous myocardial infarction. Change in the magnitude of the ST vector (STc-VM) was continuously recorded. A standardized protocol of balloon inflations was used and technetium-99m MIBI was injected intravenously at the onset of the third inflation. SPECT imaging was performed 60 minutes later and compared to a rest acquisition. SPECT was quantified by bull's-eye analysis using: (1) the change in the pathologic/normal area count ratio (delta P/N) as an index of the severity of ischemia; and (2) planimetered defect size during PTCA as an indicator of the size of the area at risk. The delta P/N from baseline to balloon occlusion (22 +/- 11%) was correlated, albeit loosely, to the maximum value of STc-VM (245 +/- 186 microV, r = 0.62, p < 0.05), but there was no correlation between the size of the scintigraphic defect and STc-VM. Likewise, the sum of ST-segment elevation was correlated to delta P/N (r = 0.72, p < 0.02), but not to the size of the scintigraphic defect.(ABSTRACT TRUNCATED AT 250 WORDS)
The distribution of the prohormone convertases, PC1/3, PC2 and PC5/6, was determined by immunoblotting in two cell lines. In alpha TC1-6 cells, the proglucagon processing occurred according to the pancreatic A-cell type. In STC-1 cells, proglucagon was processed in a manner reminiscent of the intestinal L-cell type. PC1/3 was undetectable in both proglucagon processing cell lines whereas PC2 displayed a strong immunostaining in the alpha TC1-6 cells and was barely detectable in the STC-1 cells. PC5/6 was detected as a 70 kDa protein in both cell lines. These results suggest a possible role of PC2 in the processing of proglucagon into glucagon in the A-cells, whereas in L-cells it would require still undetermined endoproteases.
Although the haemodynamic response during submaximal supine exercise in mitral stenosis has been well described, the determinants of peak oxygen uptake during maximal upright exercise are poorly characterized and may differ in sinus rhythm and atrial fibrillation. Seventy patients with isolated mitral stenosis underwent Doppler-echocardiography and bicycle exercise with respiratory gas analysis. Forty-two patients were in sinus rhythm (Group I) and 28 in atrial fibrillation (Group II). Peak oxygen uptake was 21.3 +/- 5.6 ml.min-1.kg-1 in group I and 18.1 +/- 5.1 ml.min-1.kg-1 in group II (P < 0.05). There was no significant correlation between indices of exercise tolerance (exercise duration, ventilatory threshold, peak oxygen uptake, indexed peak oxygen uptake, peak oxygen pulse) and valve area or gradient in either group. Indexed peak oxygen uptake was not correlated to delta oxygen pulse but was linearly related (r = 0.43) to delta heart rate (delta heart rate = peak heart rate/rest heart rate) in Group I but not in Group II. Thus, in patients with mitral stenosis, no correlation was found between the mitral valve area or the gradient at rest and maximal upright exercise tolerance, suggesting that peripheral adaptation and, in sinus rhythm, chronotropic reserve, are important compensatory mechanisms.
Anaerobic threshold (AT), proposed as a non-invasive index of exercise tolerance, independent of patient motivation, is considered more reliable than exercise duration in assessing the effect of drug therapy in chronic heart failure (CHF). However, inter-observer variation in patients may be more difficult than in normal subjects. In a multicentre study, 85 patients from 10 centres performed a total of 331 bicycle maximal tests (ramp protocols, 10 watts.min-1) with respiratory gas analysis by different systems. A central committee reviewed all the tests. Percentages of AT determination ranged from 34% to 71% depending on the method used. Apart from the respiratory exchange ratio (RER) method, which yielded the lowest rate of determination: 34%, and the crossing point (when RER = 1), which yielded the highest rate, 71%, other methods of determination, such as carbon dioxide (42%), minute ventilation (52%) or ventilatory equivalents plotted vs time (57%), did not differ in the rate of AT determination. Thus, even among trained physicians, AT determination was not reliable. The crossing point may nevertheless be a valuable index from a pragmatic standpoint, although it occurs after the actual AT. Peak oxygen uptake should remain the main end-point in assessment of exercise capacity.
The general opinion that treadmill exercise elicits circulatory reserve more than bicycle exercise derives from studies conducted in normal subjects or subjects with coronary artery disease. To investigate if this also occurs in patients with chronic heart failure (CHF), 40 patients (mean ejection fraction: 26 +/- 9 percent) with normal pulmonary function underwent in random order both treadmill (Naughton modified protocol, holding on handrails permitted) and bicycle (10 W/min) maximal exercise over a 1-week period. Peak oxygen uptake (19.6 +/- 5.3 vs 17.6 +/- 5.1 ml/min/kg, p < 0.0001), ventilatory threshold (14.4 +/- 4.7 vs 12.0 +/- 3.5 ml/min/kg, p < 0.0001), and minute ventilation (59 +/- 18 vs 55 +/- 15 L/min, p < 0.05) were greater on treadmill than on bicycle. Heart rate, systolic blood pressure, breathing rate, respiratory exchange ratio, perceived exertion scale, and lactate were identical. The coefficient of the correlation between oxygen uptake and time was greater with bicycle than with treadmill (r = 0.97 +/- 0.04 vs 0.90 +/- 0.07, p < 0.001). Thus, treadmill exercise is more suitable for determining peak oxygen uptake in patients with CHF. However, the increase in oxygen uptake is more regular with bicycle exercise.
Cardiac transplantation has transformed the prognosis of NYHA Class IV severe cardiac failure. However, despite a "new heart", the exercise tolerance of transplanted patients remains poor for a long time. Cardiac denervation which decreases the chronotropic reserve, diastolic left ventricular dysfunction and intrinsic muscular abnormalities related to lack of training and to treatment are the underlying causes.
Scales of quality of life have only recently been imposed in cardiology. Essentially an Anglosaxon invention, they have been used for evaluating most treatment of cardiac failure. The main qualities of a good quality of life questionnaire are its sensitivity, its reproducibility and its validity. The contents of the questionnaire, particularly the relationship between items concerning symptoms and those concerning the psychological aspects of the disease, have a great influence on the quality of results. The "Living with Heart Failure Questionnaire" of the University of Minnesota is the most validated questionnaire at present. As with most other methods of therapeutic assessment in cardiology, the most recently obtained results from large multicenter trials, seem to show a much smaller benefit of drugs reputed to be effective in this condition, with respect to the quality of life of patients. This justifies: the continuation of validation of these questionnaires, a reflection on the efficacy of classical management of these patients.
The essential goal of medical treatment following myocardial infarction with left ventricular dysfunction must be the prevention of secondary cardiac failure. The existence of left ventricular dysfunction, in particular when it is not accompanied by clinical cardiac failure, is a virtually formal indication for beta-blocker treatment after an infarction. Beta-blockers with intrinsic sympathomimetic activity (ISA) are possibly better tolerated in this context. However, experience shows that cardiologists and general practitioners often remain reluctant to prescribe beta-blockers whenever left ventricular function is impaired. Converting enzyme inhibitors decrease the risk of onset of secondary cardiac failure, reduce sudden deaths by ventricular arrhythmias, reduce recurrences of myocardial infarction or unstable coronary insufficiency, and more generally reduce overall and cardiovascular mortality. This is a class effect. While there is no urgency to prescribe them during the acute phase, it is generally considered that it is extremely useful to give them fairly quickly, i.e. during the first 72 hours. At the end of the hospital phase, around two weeks, it is desirable, whenever possible, to prescribe a dose of the order of 75 mg/day of captopril or 2.5 mg/day of ramipril. The administration of aspirin can be considered virtually routine. Oral anticoagulants are desirable in the presence of a large akinetic pocket, a frequent starting point of thrombosis and/or systemic emboli, or in the presence of atrial fibrillation. Digitalis/diuretic treatment does not appear to be indicated at this stage. Other types of anti-ischemic treatment are not theoretically indicated as a matter of principle at this stage in the absence of residual ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular failure leads to circulatory failure which causes clinical symptoms and in which regional blood flow changes play an important role. An abnormality of systemic vasodilatation on exercise or on pharmacological intervention has been shown. This affects both the resistance and conductive vessels and is mainly functional, related to neurohormonal stimulation with a predominance of vasoconstrictive factors amongst which increased adrenergic tone probably plays an essential part. A modification of the endothelium-dependent response has recently been confirmed. The presence of structural vascular abnormalities (increase in parietal sodium and water concentrations, "remodelling" remains debatable in the human. These abnormalities have a common factor in their chronicity and take time to regress with medical treatment or after cardiac transplantation. Physical training seems to induce more marked and, above all, more rapid effects.
OBJECTIVE: To clarify the spectrum of the left ventricular responses in hypertension in man by means of coupled analysis of elastances. In the present study we analysed the 'functional' coupling of the left ventricle and the arterial system in terms of the arterial effective elastance (E(a)) divided by a value of end-systolic left ventricular elastance approximated by the end-systolic pressure-volume ratio (E(lv)). METHODS: Twenty-five normotensive and 19 hypertensive males without heart failure underwent a haemodynamic and angiographic study. The hypertensives were divided into three subgroups: group 1 had normal ejection fraction, group 2 had ejection fraction > 70% and group 3 had ejection fraction 50-58%. RESULTS: The ejection fraction was similar in hypertensives and controls and E(lv) was significantly increased in the hypertensives. E(a) was identical in the three hypertensive subgroups, which differed only for E(lv). Hypertensives with a normal ejection fraction (n = 8) had a normal E(a)/E(lv) ratio and end-systolic stress, and a significantly increased E(lv), related mainly to an increase in the left ventricular mass divided by the end-diastolic volume (m/VED) with normal systolic function of the left ventricular muscle. The significantly increased systolic pump function of group 2 (n = 5) seems to be related to a significant increase in both m/VED and left ventricular muscle contractility. Group 3 (n = 6) was more heterogeneous, some patients having insufficient hypertrophy and others impaired muscle function. CONCLUSIONS: The left ventricle and the arterial system remain correctly coupled in hypertensives overall, but with marked heterogeneity of the systolic pump (and sometimes muscle) function and mainly of the geometry of the left ventricle. Regarding the relatively unequivocal changes in Ea, the differences in ejection fraction and in left ventricular-arterial coupling in hypertensives are related mainly to changes in the left ventricular systolic pump function.